WO2004024702A1 - Novel carboxamide compounds having an mch-antagonistic effect, medicaments containing said compounds, and methods for the production thereof - Google Patents

Abstract

The invention relates to carboxamide compounds of general formula (I), in which the groups and radicals A, B, W, X, Y, Z, R1, R2, R3, and k have the meanings indicated in claim 1. The invention also relates to methods for producing said carboxamide compounds and medicaments containing at least one inventive carboxamide. The inventive medicaments are suitable for treating metabolic disorders and/or eating disorders, especially obesity, bulimia, anorexia, hyperphagia, and diabetes due to the MCH receptor-antagonistic activity thereof.

Description

 New carboxylic acid amide compounds having MCH antagonist activity, medicaments containing these compounds and methods of theirs

manufacturing

The present invention relates to novel carboxylic acid amide compounds, processes for their preparation and their physiologically acceptable salts and their use as MCH antagonists and their use for the production of a medicament which is used for the prophylaxis and / or treatment of phenomena and / or diseases caused by MCH or MCH in another causal relationship is appropriate. Another object of this invention relates to the use of a compound according to the invention for influencing the eating behavior as well as for reducing the body weight and / or for preventing an increase in the body weight of a mammal. Further, compositions and pharmaceutical compositions, each containing a compound of the invention, and a process for their preparation, the subject of this invention.

Background of the invention

The intake of food and its implementation in the body plays an existential role in life for all living things. Therefore, deviations in the intake and conversion of food usually lead to disorders and diseases. The change in human living and eating habits, especially in industrialized countries, has favored obesity in recent decades. Obesity directly leads to a restriction of mobility and a reduction in the quality of life for those affected. To make matters worse, obesity often results in other diseases, such as diabetes, dyslipidaemia, high blood pressure, arteriosclerosis and coronary heart disease. In addition, the high body weight alone leads to an increased burden on the musculoskeletal system, which can lead to chronic complaints and diseases such as arthritis or osteoarthritis. Thus, obesity represents a serious health problem for society. The term obesity means an excess of adipose tissue. In this context, obesity is basically considered to be any increased level of obesity leading to a health risk. A distinction between normal and obesity-related individuals is ultimately not exactly possible, but the health risk associated with obesity probably increases continuously with increasing adiposity. For the sake of simplicity, in the context of the present invention, preferably the individuals having a body mass index (BMI) defined as the kilogram of body weight divided by height (in meters) squared are above the value of 25, especially above 30, as suffering from obesity.

Apart from physical activity and dietary changes, there is currently no convincing treatment option for effectively reducing body weight. However, as obesity is a high risk factor in the development of serious and even life-threatening diseases, it is even more important to provide pharmaceutical agents for the prophylaxis and / or treatment of obesity. One recently proposed approach is the therapeutic use of MCH antagonists (inter alia WO 01/21577, WO 01/82925).

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide consisting of 19 amino acids. It is mainly synthesized in the hypothalamus in mammals and reaches further brain regions via the projections of hypothalamic neurons. Its biological activity is mediated in humans by two distinct glycoprotein-coupled receptors (GPCRs) from the family of rhodopsin-related GPCRs, MCH receptors 1 and 2 (MCH-1R, MCH-2R).

Studies of the function of MCH in animal models provide good evidence for a role of the peptide in the regulation of the energy balance, ie alteration of metabolic activity and feed intake [1, 2]. For example, after intraventricular administration of MCH in rats, the Feed intake increased compared to control animals. In addition, transgenic rats that produce more MCH than control animals respond after administration of a high-fat diet with greater weight gain than animals with non-experimentally-altered MCH levels. It has also been found that there is a positive correlation between periods of increased craving for food and the amount of MCH mRNA in rat hypothalamus. Of particular relevance for the function of MCH, however, are experiments with MCH knock out mice. A loss of the neuropeptide leads to leaner animals with reduced fat mass, which consume significantly less food than control animals.

The anorectic effects of MCH are mediated by the Gαs- coupled MCH-1 R in rodents [3-6]. In contrast to primates, ferrets and dogs, no other receptor has been detected in rodents so far. After losing the MCH-1 R, knock-out mice have less fat mass, increased energy expenditure and, on a high-fat diet, no weight increase compared to control animals. Another indication of the importance of the MCH-MCH-1 R system in energy balance regulation comes from experiments with a receptor antagonist (SNAP-7941) [3]. In long-term experiments, the animals treated with the antagonist lose significant weight.

In addition to its anorexic effect, the MCH-1 R antagonist SNAP-7941 provides further anxiolytic and antidepressant effects in behavioral experiments with rats [3]. Thus, there is clear evidence that the MCH-MCH-1 R system is involved not only in the regulation of the energy balance but also the affectivity.

Literature:

1. Qu, D., et al., A role for melanin-concentrating hormone in the central regulation of feeding behavior. Nature, 1996. 380 (6571): p. 243-7.

2. Shimada, M., et al., Mice Lacking melanin-concentrating hormones are hypophagic and lean. Nature, 1998. 396 (6712): p. 670-4. 3. Borowsky, B., et al., Antidepressant, anxiolytic and anorectic effects of melanin-concentrating hormone-1 receptor antagonist. Nat Med, 2002. 8 (8): p. 825-30.

4. Chen, Y., et al., Targeted disruption of the melanin-concentrating hormone receptor- 1 results in hyperphagia and resistance to diet-induced obesity.

Endocrinology, 2002. 143 (7): p. 2469-77.

5. Marsh, D., et al., Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Be U S A, 2002. 99 (5): p. 3240-5. 6. Takekawa, S., et al., T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur J Pharmacol, 2002. 438 (3): p. 129-35.

In the patent literature, certain amine compounds are suggested as MCH antagonists. Thus, in WO 01/21577 (Takeda) compounds of the formula

in der Ar¹ eine cyclische Gruppe , X einen Spacer, Y eine Bindung oder einen Spacer, Ar einen aromatischen Ring, der mit einem nicht-aromatischen Ring kondensiert sein kann, R¹ und R² unabhängig voneinander H oder eine Kohlenwasserstoff-Gruppe bedeuten, wobei R¹ und R² zusammen mit dem angrenzenden N-Atom einen N-haltigen Heteroring bilden können und R² mit Ar auch einen spiroeyclischen Ring bilden kann, R zusammen mit dem angrenzenden N-Atom und Y einen N-haltigen Heteroring bilden kann, als MCH- Antagonisten zur Behandlung von u.a. Obesitas beschrieben.

in Ar ¹ a cyclic group, X a spacer, Y a bond or a spacer, Ar an aromatic ring which may be condensed with a non-aromatic ring, R ¹ and R ² independently of one another denote H or a hydrocarbon group, where R ¹ and R ² together with the adjacent N atom can form an N-containing hetero ring and R ² with Ar can also form a spiro-cyclic ring, R together with the adjacent N atom and Y can form an N-containing hetero ring, described as MCH antagonists for the treatment of, inter alia, obesity.

Furthermore, in WO 01/82925 (Takeda) also compounds of the formula

in der Ar¹ eine cyclische Gruppe , X und Y Spacer-Gruppen, Ar einen gegebenenfalls substituierten kondensierten polycyclischen aromatischen Ring, R¹ und R² unabhängig voneinander H oder eine Kohlenwasserstoff-Gruppe bedeuten, wobei R¹ und R² zusammen mit dem angrenzenden N-Atom einen N- haltigen heterocyclischen Ring bilden können und R² zusammen mit dem angrenzenden N-Atom und Y einen N-haltigen Heteroring bilden kann, als MCH- Antagonisten zur Behandlung von u.a. Obesitas beschrieben.

in Ar ^1, a cyclic group, X and Y spacer groups, Ar an optionally substituted condensed polycyclic aromatic ring, R ¹ and R ^{2 are} independently H or a hydrocarbon group in which R ¹ and R ² together with the adjacent N atom can form an N-containing heterocyclic ring and R ² together with the adjacent N atom and Y can form an N-containing hetero ring, as MCH antagonists for the treatment of including obesity.

Further amine compounds with MCH antagonist activity are proposed in WO 02/057233 (Schering Corp.). The compounds fall under the general formula

worin Ar¹, Ar², Ar³ u. a. Aryl oder Heteroaryl, X O, S oder N-CN, Y eine Einfachbindung oder Cι- -Alkylen bedeuten sowie R¹ und R² die angegebenen Bedeutungen besitzen.

wherein Ar ¹ , Ar ² , Ar ^3, inter alia, aryl or heteroaryl, XO, S or N-CN, Y is a single bond or Cι- alkylene and R ¹ and R ^{2 have} the meanings indicated.

Likewise, an MCH antagonistic action is described in WO 02/051809 (Schering Corp.) in connection with piperidine derivatives of the formula

in der W eine näher definierte Aminocarbonyl- oder Carbonylamino-Gruppe, X - CHR⁸, -CO-, -C(=NOR⁹)- oder -CR⁸=, Y CH, C(OH), C(Cι_-4-Alkoxy) oder im Falle einer Doppelbindung C, R² eine substituierte Aryl- oder Heteroarylgruppe, R¹⁰ H, Cι-6-Alkyl oder Aryl bedeuten und die übrigen Reste die angegebene Bedeutung besitzen.

in the W a more defined aminocarbonyl or carbonylamino group, X - CHR ⁸ , -CO-, -C (= NOR ⁹ ) - or -CR ⁸ =, Y is CH, C (OH), C (Cι _-4 - Alkoxy) or in the case of a double bond C, R ^{2 is} a substituted aryl or heteroaryl group, R ^{10 is} H, C 6 -alkyl or aryl and the remaining radicals have the meaning indicated.

Carboxylic acid amides as antagonists of the human 11CBy receptor are proposed in WO 02/10146 (Smithkline Beecham). The compounds are representatives of the general structural formula

in the AH, alkyl, alkoxy, alkenyl, acyl, halogen, OH, CN or CF ₃ , R ^{3 is} H, methyl or ethyl, R ^{4 is} an optionally substituted aromatic carbocyclic or heterocyclic ring, Z is O, S, NH, CH ₂ or a Single bond, R ^{5 is} an optionally substituted aromatic, saturated or unsaturated carbocyclic or heterocyclic ring, Q is the group -XY-NR ¹ (R ² ), wherein according to different cases XO, S or N, Y is an alkylene or a cycloalkylene group which may also be substituted, and R ¹ and R ^{2 may be} alkyl or phenyl-alkyl, wherein R ¹ and R ² , R ¹ and Y or R ¹ and X may also be linked together to form a ring system as indicated ,

Further compounds with MCH antagonistic properties are proposed in the publications WO 03/035055, WO 03/033480, WO 02/06245, WO 02/04433, WO 01/87834, WO 01/21169 and JP 2001/226269.

Quinazolinone compounds of the general formula

are described in WO 01/23365 (Merck), wherein Z is a bond or phenylene, and in WO 01/23364 (Merck), wherein Z is cyclohexylene. Further, Y is a bond or C ₂ - alkenyl and R ^{4 is} aryl, cycloalkyl, phenylalkyl or a heterocyclic system. These compounds are described as GPIblX inhibitors, in particular as inhibitors of this receptor with the von Willebrand factor (vWF) ligands. In addition, aromatic compounds that may contain an amide bridge and an amine group are suggested in the literature for other indications. Thus, in WO 99/01127 (Smithkline Beecham Corp.) compounds of the general formula Ar-AE, wherein Ar is an optionally substituted aromatic mono- or bicyclic group, A is an amide or amine bridge and E, inter alia, a phenyl group which in para Position via a spacer group B substituted with a substituted aminoalkylene group described. These compounds are proposed as CCR5 receptor ligands for the treatment of, among others, asthma, atopic diseases and rheumatoid arthritis.

WO 01/72712 (Cor Therapeutics Inc.) describes isoquinoline compounds of the following formula

in der A eine gegebenenfalls substituierte Amino- oder Amidino-Gruppe, Z eine Bindung oder einen Alkyl-, Cycloalkyl-, Alkenyl, Alkinyl oder Aryl-Spacergruppe, m und n 0 bis 3, D eine Bindung oder eine angegebene Brücke, X NR¹² oder CHR¹², p 0 bis 3, E neben angegebenen Ether-, Amin-, Amid und Carboxylgruppen auch eine Bindung, J eine Bindung, eine Cycloalkylen-, Phenylen-, Naphthylen- oder Heteroaryl-Gruppe, G eine näher spezifizierte Amid-, Imino- oder Amidino- Gruppen bedeuten und die übrigen Reste die angegebenen Bedeutungen besitzen. Diese Verbindungen werden als Inhibitoren des isolierten Faktors Xa sowie der Blutkoagulation und damit als antithrombotische und trombolytische Wirkstoffe vorgeschlagen.

in the A is an optionally substituted amino or amidino group, Z is a bond or an alkyl, cycloalkyl, alkenyl, alkynyl or aryl spacer group, m and n is 0 to 3, D is a bond or a given bridge, X is NR ¹² or CHR ¹² , p 0 to 3, E in addition to specified ether, amine, amide and carboxyl groups and a bond, J is a bond, a cycloalkylene, phenylene, naphthylene or heteroaryl group, G is a specified amide, Imino or amidino groups and the remaining radicals have the meanings indicated. These compounds are proposed as inhibitors of the isolated factor Xa and blood coagulation and thus as antithrombotic and trombolytic agents.

In DE 197 18 181 A1 (Boehringer Ingelheim) disubstituted bicyclic heterocycles of the formula

R- A- Het-Ar- E wherein R _{a is} one of more specified amino groups or optionally also an R _4- SO ₂ -NR 5 or R ₄ -SO ₂ group with the meanings given for R ₄ and R ₅ , A is a phenylene-C ₃ - alkylene group, an nC ₂ - ₆ alkylene group or a C ₅ -7-cycloalkylene-Cι _-3 - alkylene group which may be substituted as specified, Het is an optionally substituted benzimidazole, indole, tetrahydroquinolinone or quinazolinone group, Ar is an optionally substituted phenylene , Naphthylene, thienylene, thiazolylene, pyridinylene, pyrimidinylene, pyrazinylene or pyridazinylene group and E represents a cyano or R _b NH-C (= NH) group, in which R _b H, OH, represents Cι _-3 alkyl or an in vivo cleavable radical. These compounds are proposed as thrombin-inhibiting and thrombin-prolonging agents.

OBJECT OF THE INVENTION It is an object of the present invention to show novel carboxylic acid amide compounds, in particular those which have activity as MCH antagonists. It is also an object of this invention to provide novel carboxylic acid amide compounds that allow mammalian eating habits to be controlled and, particularly in mammals, to achieve body weight reduction and / or prevent body weight gain. Further, it is an object of the present invention to provide novel medicaments suitable for the prophylaxis and / or treatment of phenomena and / or diseases caused by MCH or in another causal relationship with MCH. In particular, it is the object of the present invention to provide medicaments for the treatment of metabolic disorders, such as obesity and / or diabetes, as well as diseases and / or disorders associated with obesity and diabetes. Further objects of the present invention relate to the demonstration of advantageous uses of the compounds of the invention. It is also an object of this invention to provide a process for the preparation of the carboxylic acid amide compounds of the invention. Other objects of the present invention will become apparent to those skilled in the art directly from the foregoing and following embodiments. Subject of the invention

A first subject of the present invention are carboxylic acid amide compounds of general formula I.

in the

R ^1, R ² are independently H, an optionally substituted Cι ¹¹ _-8 alkyl or C ₃ -7-cycloalkyl group or an optionally monosubstituted with the group R by the group R ¹² or singly, multiply, and / or nitro substituted phenyl radical, or

R ¹ and R ² form a C ₂ - ₈ alkylene bridge in which

one or two -CH 2 groups can be replaced independently of one another by -CH =N- or -CH =CH- and / or

one or two -CH ₂ groups can be replaced independently of one another by -O-, -S-, -CO-, -C (CHCH ₂ ) - or -NR ¹³ - such that heteroatoms are not directly linked to one another,

wherein one or more H atoms in the above-defined alkylene bridge may be replaced by R ¹⁴ , and / or

wherein the previously defined alkylene bridge may be substituted with one or two identical or different carbo- or heterocyclic groups Cy such that the bond between the alkylene bridge and the group Cy

via a single or double bond, via a common C atom with formation of a spirocyclic ring system, via two common, adjacent C and / or N atoms to form a fused bicyclic ring system or

- takes place via three or more C and / or N atoms to form a bridged ring system,

R ³ H, de-alkyl, C _3-7 cycloalkyl, C ₃ -7-cycloalkyl-C _1-4 alkyl-, C3-7-

Cycloalkenyl, C ₃ -7-Cycloalkenyl-Cι. alkyl, phenyl, phenyl-d- _4- alkyl, Cι- ₃ -alkoxy-C2- ₆ -alkyl, amino-C ₂ - ₆ alkyl, C ₃ -alkyl-amino-C ₂ - ₆ -alkyI or di (C _1-3 alkyl) amino C 2-6 alkyl,

X is a single bond or a d-β-alkylene bridge in which

- one or two -CH ₂ groups can be replaced independently of one another by -CH =CH- or -C≡C- and / or

- One or two -CH ₂ groups independently of one another by -O-, -S-, - (SO) -, - (S0 ₂ ) -, -CO- or -NR ⁴ - may be replaced such that in each case two O -, S or N atoms or an O- are not directly connected to an S atom,

wherein one or two C atoms independently of one another with a hydroxy, ω-hydroxy-C ₃ -alkyl, co- (C ₃ -alkoxy) -Cι- ₃ -alkyl- and / or -C-

₃ alkoxy radical and / or in each case with one or two identical or different -C _-6 alkyl radicals may be substituted, and / or

wherein the alkylene bridge may be linked to R ¹ including the N atom joined to R ¹ and X to form a heterocyclic group,

Z is a Cι _-4 -alkylene bridge, wherein two adjacent carbon atoms can be connected to each other with an additional Cι _-4- alkylene bridge, wherein in the group Z is a -CH ₂ group by -O- or -NR ⁵ - can be replaced,

where one or two C atoms of the alkylene bridge are independent each other with a hydroxy, ω-hydroxy-C-ι-3-alkyl, ω- (Cι_ ₃ -alkoxy) -Cι-3-alkyl, Cι _-3 alkoxy radical, amino-C _1-3 alkyl, Cι _-3 alkyl-amino-Cι _-3 - alkyl or di- (. _Cι-C3 alkyl) amino-Cι _-3 alkyl and / or with same or different one or two Cι _-6 alkyl residues may be substituted, and / or

wherein R ^{3 may be} joined to Z including the N atom joined to R ³ to form a heterocyclic group,

independently one of the meanings given for Cy,

wherein R ^{1 may be} joined to Y including the group X and the N atom joined to R ¹ and X to form a heterocyclic group fused to Y, and / or

wherein R ^{3 may be} joined to Y including the group Z and the N atom connected to R ³ and Z to form an anlY condensed, saturated or partially unsaturated heterocyclic group, or

where A and R ³ can be connected to each other in such a way that

the group of formula I

a group of the partial formula II

bedeutet und

means and

Q is a group selected from the partial formulas IIIa to IIIg

- CR ⁶ R ⁷ - Ula

- CR ⁶ = CR ⁷ l'lb

- N = CR ⁸ H ^{| c}

- N = N IIId CO NR ^{9 "le} N CR Ulf CO IIIg

L ¹ , L ² , L ^3, independently of one another, have the meanings given for R ²⁰ ,

B Cι _-6 -alkyl, _-6 alkenyl, Cι _-6 alkynyl, C _3- 7-Cyc] Oalkyl-Cι _-3 alkyl, C _3-7 -

Cycloalkenyl Cι-3-alkyl, C _3-7 -CycloaIkyl-Cι _-3 alkenyl or C. _{3 7} - CycloalkyI -Cι- ₃ alkynyl-, in which one or more carbon atoms may be mono- or polysubstituted by halogen and / or simply with hydroxy or cyano and / or cyclic groups mono- or polysubstituted with R ²⁰ , or

one of the meanings given for Cy, wherein the bond to the

Group W or, if appropriate, directly to the group A via a C atom of the carbocyclic part or of the optionally fused phenyl or pyridine ring or via an N or C atom of the heterocyclic part,

for the case k = 0, the group B with the group A via a common carbon atom to form a spirocyclic

Ring system or can be connected to each other via two common, adjacent atoms to form a fused, bicyclic ring system,

W is a single bond, -O-, a Cι _-4 alkylene, C _2-4 alkenylene, C 2-4

Alkynylene, Cι _-4 alkyleneoxy, oxy-Cι _-4 alkylene, C1-3 alkylene-oxy-C1.3- alkylene, imino, N- (Cι _-3 alkyl) -imino- , imino Cι- ₄ alkylene, N- (Cι _-3 - alkyl) -imino-Cι-4-alkylene, alkylene-imino- or Cι- Cι _-4 -alkylene-N- (Cι _-3 - alkyl) imino group,

wherein one or two C atoms independently of one another with a hydroxy, ω-hydroxy-Cι _-3 alkyl, α> - (Cι- ₃ alkoxy) -Cι- ₃ alkyl and / or Cι _-3 alkoxy And / or may be substituted by one or two identical or different d-β-alkyl radicals, and / or

where W in the meanings alkylene, oxyalkylene and alkyleneoxyalkylene can also be linked to B via a double bond,

k 0 or 1,

Cy is a carbo or heterocyclic group selected from one of the following meanings

a saturated 3- to 7-membered carbocyclic group, an unsaturated 5-7-membered carbocyclic group,

a phenyl group,

a saturated 4- to 7-membered or unsaturated 5- to 7-membered heterocyclic group having an N, O or S atom as heteroatom, - a saturated or unsaturated 5- to 7-membered heterocyclic

A group with two or more N atoms or with one or two N atoms and one O or S atom as heteroatoms, an aromatic heterocyclic 5- or 6-membered group with one or more identical or different heteroatoms selected from N, O and / or S,

wherein the above-mentioned 4-, 5-, 6- or 7-membered groups may be connected via two common, adjacent carbon atoms condensed with a phenyl or pyridine ring, and

where in the aforementioned 5, 6 or 7-membered groups one or two non-adjacent -CH ₂ - group by a -CO-, -C (= CH ₂ ) -,

- (SO) - or - (S0 ₂ ) - group may be replaced, and

wherein the previously mentioned saturated 6- or 7-membered groups as bridged ring systems with an imino, N- (Cι _-4 -alkyl) -imino-, methylene, Cι _-4- alkyl-methylene or di- (d _4- alkyl) methylene bridge, and

where the abovementioned cyclic groups may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , and in the case of a phenyl group may also be additionally substituted simply by nitro, and / or by one or more N atoms with R ²¹ ,

R ⁴ , R ^5, independently of one another, have the meanings given for R ¹⁶ ,

R ⁶ , R ⁷ ,

R ⁸ , R ⁹ are each independently H, a Cι- ₆ alkyl, ω-Cι _-3 alkoxy-Cι- ₃ -alkyl or α hydroxy-C _{3 -3} alkyl group and R ⁶ , R ⁷ , R ^8, independently of one another, also halogen,

R ¹¹ R ¹⁵ -0-, R ¹⁵ -0-CO-, R ¹⁶ R ¹⁷ N-, R ¹⁸ R ¹⁹ N-CO- or Cy,

R ^{12 is} one of the meanings given for R ²⁰ ,

R ^{13 is} one of the meanings given for R ¹⁷ , R ¹⁴ is halogen, Ci.E alkyl, R ¹⁵ -0-, R ¹⁵ -0-CO-, R ¹⁶ R ¹⁷ N-, R ¹⁸ R ¹⁹ N-CO-, R ¹⁵ -0-

Cι. ₃ -alkyl, R ¹⁵ -O-CO-d. _3- alkyl, R ¹⁶ R ¹⁷ Nd. ₃ alkyl, R ¹⁸ R ¹⁹ N-CO-Cι- ₃ - alkyl or Cy-Cι-3-alkyl,

R ⁵ H, Cι. _4- alkyl, Cs-7-cycloalkyl, C ₃ -7-cycloalkyl-Cι. ₃ -alkyl, phenyl, phenyl

Ci-s-alkyl or pyridinyl,

R ¹⁶ is H, Cι- ₆ alkyl, C ₃ -7-cycloalkyl, C ₃ -7-cycloalkyl-Cι. ₃ alkyl, C ₄ - ₇ - cycloalkenyl, _C4 -7 cycloalkenyl-C _1-3 alkyl, (D-hydroxy-C - ₃ alkyl,

(C ₁ -C ₃ -alkoxy) C ₂ -C ₃ -alkyl, amino-C ₁ -C ₆ -alkyl, C ₁ -C ₃ -alkyl-amino-D- _6- alkyl or di- (C 1 -C ₃ -alkyl) Amino- _6- alkyl,

R ^{17 is} one of the meanings given for R ¹⁶ or phenyl, phenyl-C. _3- alkyl, pyridinyl, dioxolan-2-yl, C ₃ -alkylcarbonyl,

_{Hydroxycarbonyl-3} Cι- alkyl, d- ₄ alkoxycarbonyl, Cι- ₃ alkylcarbonylamino-C ₂ - ₃ alkyl, Cι- ₃ alkylsulfonyl or Cι _-3 alkylsulfonylamino-C ₂ - ₃ alkyl,

R ¹⁸ , R ¹⁹ independently of one another are H or C-β-alkyl,

oder eine der für R²² angegebenen Bedeutungen,R ^{20 is} halogen, hydroxy, cyano, C 1 -alkyl, C ₃ . ₇ cycloalkyl, hydroxy-Cι- ₃ - alkyl,

or one of the meanings given for R ²² ,

R ²¹ Cι- ₃ alkyl, co-hydroxy-C ₂ - ₃ alkyl, phenyl, _phenyl-3 Cι- alkyl, C _1-3 alkyl carbonyl, carboxy, Cι- ₄ -alkoxy-carbonyl, Cι _{- 3-} alkylsulfonyl, phenylcarbonyl or phenyl-C ₃ -alkyl-carbonyl,

R ²² is pyridinyl, phenyl, phenyl-Cι _-3 alkoxy, Cι _-3 alkoxy, Cι _-3 alkylthio, carb oxy, H-CO-, Cι- ₃ alkylcarbonyl, Cι _-4 alkoxycarbonyl, aminocarbonyl,

Cι _-3 alkylaminocarbonyl, di- (Cι _-3 alkyl) aminocarbonyl, Cι-3-alkyl sulfonyl, sulfinyl Cι _-3 alkyl, Cι. _3- alkyl-sulfonylamino, amino, -C. ₃ -alkylamino, di- (d. ₃ -alkyl) -amino, phenyl-Cι.3-alkylamino or N- (C _1-3 -alkyl) -phenyl-C 1-3 -alkylamino, acetylamino, propionylamino, phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxyalkylaminocarbonyl, (4-morpholinyl) carbonyl-, (1-pyrrolidinyl) - carbonyl, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl, (4-methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonylamino or alkylaminocarbonylamino

wherein in the groups and radicals A, B, W, X, Y, Z, R ¹ to R ⁹ and R ¹¹ to R ²² each one or more carbon atoms one or more times with F and / or in each case one or two C Atoms independently of one another can be substituted simply with Cl or Br, and / or in each case one or more phenyl rings independently of one another additionally one, two or three substituents selected from the group F, Cl, Br, I, Cι. _4- alkyl, Cι- _4- alkoxy, difluoromethyl, trifluoromethyl, hydroxy, amino, C ₃ -alkylamino, di (C ₃ -alkyl) amino, acetylamino, aminocarbonyl, CN -, difluoromethoxy, trifluoromethoxy, amino-Cι- ₃ -alkyl-,

Cι- ₃ -alkylamino-C 3 -alkyl and di- (C ₃ -alkyl) -amino-C ₃ -alkyl- and / or may be substituted by nitro, and

the H atom of an existing carboxy group or an H atom bound to an N atom can each be replaced by an in-vivo leaving group,

their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

The invention also relates to the respective compounds in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates, in the form of tautomers and in the form of the free bases or the corresponding acid addition salts with pharmacologically acceptable acids. Also included in the subject matter of this invention are the compounds of the invention, including their salts, in which one or more hydrogen atoms are replaced by deuterium. Another object of the present invention is a process for the preparation of carboxylic acid amide compounds of the formula I.

wherein A, B, W, X, Y, Z, R ¹ , R ² , R ³ and k have one of the meanings given above, in which

A case of a non-connected to the group A group R ^3:

a) in the case that A is a connected via a nitrogen atom with the carboxylic acid amide nitrogen-heterocyclic group, which may have one or more heteroatoms selected from N, O and S in addition to the nitrogen atom, means at least one amine compound of Formula 1-1

in which R ¹ , R ² , R ³ , X, Y and Z have the meanings given above,

with CDT (1,1'-carbonyldi (1,2,4-triazole)) and at least one secondary amine compound of the formula I-2

A- -W- J B I-2

wherein A, B, W and k have the meanings given above and the group A is the sec. Has amine function,

is reacted in a solvent or solvent mixture in the presence of at least one base, and b) for the remaining cases at least one carboxylic acid compound of formula I-3

worin A, B, W und k die zuvor angegebenen Bedeutungen aufweisen,

wherein A, B, W and k have the meanings given above,

with TBTU (2- (1H-benzotriazol-1-yl) -1, 1, 3,3-tetramethyluronium tetrafluoroborate) and at least one amine compound of formula 1-1

worin R >1 , D R2 , _D R3 , X, Y und Z die zuvor angegebenen Bedeutungen aufweisen,

wherein R> 1, D R2, _D R3, X, Y and Z have the meanings given above,

is reacted in a solvent or solvent mixture in the presence of at least one base, and in

Case B of a radical R 3 3 linked to group A.

a) in the case of a group -CR ⁶ R ⁷ - (IIIa) having the group Q, wherein R ⁶ and R ^{7 are} as defined above, an amine compound of formula la.1

in which R ¹ , R ² , X, Y and Z have the meanings indicated, with an o-bromomethyl-benzoic acid derivative of the formula la.2

in der R⁶, R⁷, W, B und k die angegebenen Bedeutungen aufweisen, umgesetzt wird,

in which R ⁶ , R ⁷ , W, B and k have the meanings indicated, is reacted,

b) in the case of a group -CR ⁶ = CR ⁷ - (IIIb) having the group Q, wherein R ⁶ and R ^{7 are} as defined above, an isoquinolinone derivative of the formula lb.2

in which R ⁶ , R ⁷ , W, B and k have the meanings indicated, with an electrophilic compound of the formula Ib.3

in which Y and Z have the meanings indicated and OMs is a suitable leaving group, preferably mesylate, to give an isoquinoline derivative of the formula Ib.4

in which R ⁶ , R ⁷ , W, B, Y, Z and k have the meanings indicated, and the isoquinoline derivative of the formula Ib 4 is further derivatized by known processes to the compound of the formula I, c) in the case of a group -N = CR ⁸ - (IIIc) having the group Q in which R ^{8 is} as defined above, a phthalazinone derivative of the formula lc.4

in which R ⁸ , W, B and k have the meanings indicated, with an electrophilic compound of the formula Ic.5

in which Y and Z have the meanings indicated and OMs is a leaving group, preferably mesylate, to give a phthalazinone derivative of the formula Ic.6

in which R ⁸ , W, B, Y, Z and k have the meanings indicated, is reacted, and the resulting phthalazinone derivative of formula lc.6 further by known methods to the compound of formula I in which Q is -N = CR ⁸ - (IIIc), is derivatized,

d) in the case of a group having the meaning -N = N- (ldd) a o-Amino-benzamide derivative of formula ld.1

in which R ¹ , R ² , W, B, X, Y, Z and k have the meanings indicated, in the presence of a suitable nitrite compound and an acid to the compound of formula I, in which Q is -N = N- , is implemented,

e) in the case of a -CO-NR ⁹ - (llle) having group Q in which R ^{9 is} as defined above, an o-amino-benzamide derivative of the formula le.1

in which R ¹ , R ² , R ⁹ , W, B, X, Y, Z and k have the meanings indicated, in the presence of CDI (carbonyldiimidazole) to give the compound of formula I in which Q is -CO-NR ⁹ - means, is implemented,

f) in the case of a group -CR ⁸ = N- (Ulf) having group Q, in which R ^{8 is} as defined above, an o-amino-benzamide derivative of formula lf.1

in der R¹, R², W, B, X, Y, Z und k die angegebenen Bedeutungen aufweisen, mit einer Carbonsäure R⁸COOH mit der angegebenen Bedeutung für R⁸ und/oder eines entsprechenden aktivierten Carbonsäurederivats zu dem Chinazolinon- Derivat der Formel I, in der Q -CR⁸=N- bedeutet, umgesetzt wird,

in which R ¹ , R ² , W, B, X, Y, Z and k have the meanings indicated, with a carboxylic acid R ⁸ COOH as defined for R ⁸ and / or a corresponding activated carboxylic acid derivative to the quinazolinone derivative of Formula I, in which Q is -CR ⁸ = N-, is reacted,

g) in the case of the group Q having the meaning -CO- (IIIg) an isobenzofurandione derivative of the formula Ig.2

in which W, B and k have the meanings indicated, with an amine of the formula Ig.1

in which R ¹ , R ² , X, Y and Z have the meanings indicated, to the compound of formula I, in which Q is -CO-, is reacted.

Furthermore, the physiologically acceptable salts of the carboxylic acid amide compounds according to the invention described above and below are also an object of this invention.

Also an object of this invention are compositions comprising at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention in addition to optionally one or more physiologically acceptable excipients. Furthermore, medicaments comprising at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention in addition to optionally one or more inert carriers and / or diluents are the subject of the present invention.

Also an object of this invention is the use of at least one carboxylic acid amide compound of the invention and / or a salt according to the invention for influencing the eating behavior of a mammal.

Furthermore, the use of at least one carboxylic acid amide compound of the invention and / or a salt according to the invention for reducing body weight and / or preventing an increase in the body weight of a mammal is an object of this invention.

Likewise an object of the present invention is the use of at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention for the production of a medicament with MCH receptor antagonistic activity.

In addition, an object of this invention is the use of at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention for the preparation of a medicament, which for the prophylaxis and / or treatment of phenomena and / or diseases caused by MCH or with MCH in one other causal relationship is appropriate.

Another object of this invention is the use of at least one carboxylic acid amide compound of the invention and / or a salt according to the invention for the manufacture of a medicament, soft for the prophylaxis and / or treatment of metabolic disorders and / or eating disorders, in particular of obesity, bulimia, bulimia nervosa, cachexia , Anorexia, anorexia nervosa and hyperphagia, is suitable. Likewise an object of this invention is the use of at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention for the preparation of a medicament which is used for the prophylaxis and / or treatment of obesity-associated diseases and / or disorders, in particular diabetes, especially type II Diabetes, diabetic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, insulin resistance, pathological glucose tolerance, encephalorrhagia, cardiac insufficiency, cardiovascular diseases, especially arteriosclerosis and hypertension, arthritis and gonitis.

In addition, the present invention has the use of at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention for the manufacture of a medicament which is used for the prophylaxis and / or treatment of hyperiipidemia, cellulitis, fat accumulation, malignant mastocytosis, systemic mastocytosis, emotional disorders, affective disorders, Depression, anxiety, sleep disorders, reproductive disorders, sexual disorders, memory disorders, epilepsy, forms of dementia and hormonal disorders.

Another object of this invention is the use of at least one carboxylic acid amide compound of the invention and / or a salt of the invention for the manufacture of a medicament useful in the prophylaxis and / or treatment of voiding disorders such as urinary incontinence, overactive bladder, urinary urgency, nocturia and enuresis.

In addition, an object of this invention relates to processes for the preparation of a medicament according to the invention, characterized in that at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention is incorporated into one or more inert carriers and / or diluents by non-chemical means.

A further subject of this invention is a medicament containing a first active substance which is selected from the carboxylic acid amide And a second active ingredient selected from the group consisting of active ingredients for the treatment of diabetes, agents for the treatment of diabetic complications, agents for the treatment of obesity, preferably other than MCH antagonists, active ingredients Treatment of hypertension,

Active ingredients for the treatment of hyperlipidemia, including arteriosclerosis, agents for the treatment of arthritis, drugs for the treatment of anxiety and drugs for the treatment of depression, optionally with one or more inert carriers and / or diluents.

Detailed description of the invention

Unless indicated otherwise, the groups, radicals, substituents and indices have, in particular A, B, W, X, Y, Z, R ¹ to R ⁹ , R ¹¹ to R ²² , L ¹ , L ² , L ³ and k, one of the meanings given above and / or below.

A preferred embodiment of this invention comprises compounds of the formula I in which

R ^{3 is} H, C 1-e-alkyl, C _3-7 -cycloalkyl, C ₃ . ₇ -cycloalkyl-Cι. _4- alkyl-, C _1-3 -alkoxy-

C2-β-alkyl, amino-C _2- 6 alkyl, Cι. _3- alkyl-amino-C ₂ - ₆ -alkyl- or di- (C ₃ -alkyl) -amino-C ₂ - ₆ -alkyl-,

B is one of the meanings given for Cy, wherein the bond to the

Group W or, if appropriate, directly to the group A via a C atom of the carbocyclic part or of the optionally fused phenyl or pyridine ring or via an N or C atom of the heterocyclic part,

wherein for the case k = 0, the group B with the group A via a common carbon atom to form a spirocyclic ring system or can be connected to each other via two common, adjacent atoms to form a fused, bicyclic ring system,

a carbo or heterocyclic group selected from one of the following meanings

a saturated 3- to 7-membered carbocyclic group,

an unsaturated 5- to 7-membered carbocyclic group,

a phenyl group, a saturated 4- to 7-membered or unsaturated 5- to 7-membered heterocyclic group having an N, O or S atom as heteroatom,

a saturated or unsaturated 5- to 7-membered heterocyclic group having two or more N atoms or having one or two N atoms and one O or S atom as heteroatoms,

an aromatic heterocyclic 5- or 6-membered group with one or more identical or different heteroatoms selected from N, O and / or S,

wherein the above-mentioned 5-, 6- or 7-membered groups may be connected via two common, adjacent carbon atoms condensed with a phenyl or pyridine ring, and

wherein in the aforementioned 5, 6 or 7-membered groups a -CH ₂ group is replaced by a -CO-, -C (= CH ₂ ) -, - (SO) - or - (S0 ₂ ) - group can be, and

wherein the previously mentioned saturated 6- or 7-membered groups as bridged ring systems with an imino, N- (Cι- ₃ - alkyl) -imino-, methylene, -C. _3- alkyl-methylene or di- (Cι- ₃ -alkyl) - methylene bridge may be present, and

wherein the aforementioned cyclic groups one or more times to one or more C atoms with R ²⁰ , in the case of a phenyl group may additionally be substituted by nitro, and / or by one or more N atoms with R ²¹ ,

R ¹⁵ is H, _d-4 alkyl, C _{3rd 7} -cycloalkyl, C _3-7 -cycloalkyl-C. _3- alkyl, phenyl or phenyl-C 3-alkyl,

R ^{17 is} one of the meanings given for R ¹⁶ or

Phenyl, phenyl-C ₃ -alkyl, dioxolan-2-yl, C ₃ -alkylcarbonyl, hydroxycarbonyl-C. ₃ -alkyl-, -C ₃ -alkylcarbonylamino-C ₂ - ₃ -alkyl, Cι_ ₃ -alkylsulfonyl or C ₃ -alkylsulfonylamino-C ₂ . _3- alkyl,

R ^{22 is} phenyl, phenyl-Cι. ₃ alkoxy, Cι _-3 alkoxy, Cι. _3- alkylthio, carboxy,

C 1 -alkylcarbonyl, C _1-3 -alkoxycarbonyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl, di- (C _1-3 -alkyl) aminocarbonyl, C _1-3 -alkyl sulfonyl, C _1-3 Alkyl-sulfinyl, C _1-3 -alkyl-sulfonylamino, amino,

C _-3 alkylamino, di- (Cι _-3 alkyl) amino, phenyl-Cι _-3 alkylamino or N- (Cι _-3 alkyl) phenyl-Cι _-3 alkylamino, acetylamino , Propionylamino, phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxyalkylaminocarbonyl, (4-morpholinyl) carbonyl, (1-pyrrolidinyl) carbonyl, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl , (4-methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonylamino or alkylaminocarbonylamino

wherein in the groups and radicals A, B, W, X, Y, Z, R ¹ to R ⁹ and R ¹¹ to R ²² each one or more carbon atoms one or more times with F and / or in each case one or two C Atoms independently can be substituted simply with Cl or Br and

the H atom of an existing carboxy group or an H atom bound to an N atom can each be replaced by an in-vivo leaving group,

their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. According to the first group of the preferred embodiments, the group A and the radical R ^{3 are} not directly connected to each other. Therefore, the group A has one of the meanings given for Cy.

According to the second group of the preferred embodiments, the group A and the radical R ³ are connected to each other such that

the group of formula I

a group of the partial formula II

means and

Q is a group selected from the subformulae purple to IIIg

-CR ⁶ R ⁷ - purple,

-CR - CR'llb,

8th

-N = CR IIIc, -N = N IIId,

-CO NR- llle, CR ⁸ = N Ulf, CO III.

Of these, preferred meanings of the group Q are selected from the subformulae IIIb, IIId, IIIe, IIIf and IIIg, in particular IIId, IIIe, IIIf and IIIg.

Preferred meanings of the substituents R ^6, R ^7, R ⁸ and R ⁹ are independently H and Cι _-4 alkyl, in particular H, methyl or ethyl.

The substituents L ¹ , L ² , L ³ independently of one another preferably have one of the following meanings H, F, Cl, Br, CH ₃ , CHF ₂ , CF ₃ , C ₂ H ₅ , C ₃ H ₇ , CH (CH ₃ ) ₂ , OCH ₃ , OCHF ₂ , OCFs, OC ₂ H 5, OC ₃ H 7 and OCH (CH ₃ ) ₂ .

Preferably, only one of the substituents L ¹ , L ² , L ^{3 has} a meaning other than H, in particular one of the meanings given above as preferred. Particularly preferably, all three substituents L ¹ , L ² , L ³ H.

Preferably, the radicals R ^1, R ² are independently H, Cι _-6 alkyl, _C3-7 mean - cycloalkyl, C ₃ - ₇ cycloalkyl-Cι _alkyl-3, co-hydroxy-C ₂ -s-alkyl -, ₍₃ Cι- alkoxy) ω- - C _2-3 alkyl, Cι _{-4 -alkoxy-carbonyl-3} Cι- alkyl, alkyl amino-C _2-4 alkyl _-3 Cι _amino-2- C 4-alkyl or di- (Cι _-3 alkyl) amino-C ₂ - ₄ alkyl, phenyl or _phenyl-3 Cι- alkyl, wherein, in the above-mentioned groups and radicals or more C atoms can be mono- or polysubstituted with F and / or one or two C atoms independently of one another with Cl or Br, and where the phenyl radical is mono- or polysubstituted by the previously defined R ¹² radical and / or simply may be substituted with nitro.

Most preferably, the radicals R ¹ , R ^{2 are} independently C ¹ -C ₄ -alkyl, C ₃ . ₇ -cycloalkyl, C _3-7 -cycloalkyl-C ₃ -alkyl-, ω-hydroxy-C ₂ - ₃ -alkyl-, ω- (C _1-3 -alkoxy) -C ₂ . ₃ -alkyl, Cι. _4- alkoxy-carbonyl -C. ₃ -alkyl-, where one of the radicals R ¹ , R ^{2 can} also be H. Further preferably, R ¹ and R ^{2 form} an alkylene bridge such that R ¹ R ² N- is a group selected from azetidine, pyrrolidine, piperidine, azepane, 2,5-dihydro-1 H-pyrrole, 1, 2,3, 6-tetrahydro-pyridine, 2,3,4,7-tetrahydro-1H-azepinyl, 2,3,6,7-tetrahydro-1H-azepine, piperazine, wherein the free imine function may be substituted with R ¹³ , Morpholine and thiomorpholine, according to the general definition of R ¹ and R ^2, one or more H atoms may be replaced by R ¹⁴ , and / or the aforementioned groups in one according to the general definition of R ¹ and R ² in the manner indicated with one or two identical or different carbo- or heterocyclic Cy groups can be substituted.

eine Bedeutung gemäß einer der folgenden TeilformelnMost preferably, the group has

a meaning according to one of the following sub-formulas

wherein one or more H atoms of the heterocycle formed by the group R ¹ R ² N- may be replaced by R ¹⁴ and the ring connected to the heterocycle formed by the group R ¹ R ² N- one or more times on one or more several C atoms with R ²⁰ , in the case of a phenyl ring also in addition may be substituted with nitro.

Very particular preference is given to the groups R ¹ R ² N- described above in which R ¹ and R ² with the N atom of the group R ¹ R ² N- are a pyrrolidine, piperidine or 2,5-dihydro-1H-pyrrole Ring, which may be substituted as indicated.

Preferred meanings of the group R ¹⁴ are Cι- alkyl, Cι_ ₄ -cycloalkyl, hydroxy, -C. ₄ -alkoxy, Cι- _4- alkoxy-C-ι- ₃ -alkyl-, hydroxy-Cι. ₃ -alkyl-, Cι- ₄ -alkyl- carbonyl, -C. ₄ -alkoxy-carbonyl, _{Cι-4-alkoxy-carbonyl-3} Cι- alkyl, Cι- carbonylamino ₄ alkoxy, Cι.4-alkoxy-carbonylamino-C -3 alkyl, amino, (Cι - _4- alkyl) -amino, di- (Cι- ₄ alkyl) -amino, phenyl, phenyl-oxy, pyridinyl, pyridinyl-oxy.

A preferred, substituted with the group Cy piperidine group has the

wie angegeben substituiert sein kann.Structure wherein Cy is preferably phenyl, the

as indicated may be substituted.

Preferably, the alkylene bridge X has no or at most a -NR ⁴ - group. The position of the NR ⁴ group within the alkylene bridge X is preferably selected such that together with the amino group NR ¹ R ² or another adjacent amino group no aminal function is formed or two N atoms are adjacent to one another. Therefore, in the case where a -CH ₂ group is replaced by -NR ⁴ -, the alkylene bridge preferably has the meaning C ₂ . ₇ - alkylene-NR ⁴ -C ₀ -5-alkylene, wherein the bridge X in addition to the N-atom has a maximum of 7 bridging carbon atoms and wherein the carbon atoms may be substituted in the manner indicated.

X is preferably a single bond or an unbranched bridge selected from C ₁ -C ₆ -alkylene, C ₂ . _6- alkenylene, C ₂ -6-alkynylene, d-β-alkyleneoxy, carbonyl, carbonyl-Cι- ₆ -alkylene or Cι- ₆ -alkylene-amino, wherein the amino group may be substituted with R ⁴ , wherein one or two C atoms may be substituted according to the manner given in the general definition of X. and / or the alkylene bridge may be joined to R in the manner indicated.

More preferably, X is a single bond, carbonyl or an alkylene bridge selected from methylene, 1,2-ethylene, 1,3-propylene and 1,4-butylene, wherein one or two C atoms independently of one another with a hydroxy, ω -Hydroxy-C _1-3 -alkyl-, ω- (C _1-3 -alkoxy) -C _1-3 -alkyl and / or C _1-3 -alkoxy radical and / or in each case with one or two identical or different C 1 - Alkyl radicals may be substituted, and wherein in each case one or more C atoms mono- or polysubstituted with F and / or in each case one or two C atoms may be independently substituted with Cl or Br independently.

If one or two C atoms in the group X are substituted by a hydroxyl and / or C _1-3 alkoxy radical, the substituted C atom is preferably not directly linked to an amino group, in particular -NR ¹ R ² or -NR ⁴ -, adjacent.

A very particularly preferred meaning of the bridge X is a single bond, -CH ₂ - or -CH (CH ₃ ) -.

In the event that in the bridge Z a -CH ₂ group is replaced by -NR ⁵ -, the position of the NR ⁵ group within the group Z is preferably selected such that together with the amino group -NR ³ - or one other adjacent amino group no aminal function is formed or two N atoms are adjacent to each other.

Preferred meanings of the bridge Z are methylene, 1,2-ethylene, 1,3-propylene, 1,4-butylene, methyleneoxy, 1,2-ethyleneoxy, 1,3-propyleneoxy and 1,4-butyleneoxy, wherein one or two C atoms independently of one another with a hydroxy, ω-hydroxy-Cι. ₃ -alkyl-, ω- (-C ₃ -alkoxy) -Cι- ₃ -alkyl- and / or Cι_ ₃ -alkoxy radical and / or in each case be substituted by one or two identical or different Cι- _4- alkyl radicals can, and wherein in each case one or more C atoms mono- or polysubstituted with F and / or in each case one or two C atoms independently of one another can be substituted simply with Cl or Br and wherein R ³ with Z may be connected to form a heterocyclic group including the N atom joined to R ³ .

If one or two C atoms in the group Z are substituted by a hydroxyl and / or C ₁ -3 alkoxy radical, the substituted C atom is preferably not directly linked to an amino group, in particular -NR ³ - or -NR ⁵ -, adjacent.

Z is particularly preferably selected from the group -CH ₂ -, -CH ₂ -CH ₂ -, -CH ₂ -CH (CH ₃ ) -, -CH ₂ -C (CH ₃ ) ₂ -, -CH (CH ₃ ) -CH ₂ -, -C (CH ₃ ) ₂ -CH ₂ - and -CH ₂ -O-, in particular -CH ₂ -CH ₂ - or -CH (CH ₃ ) -CH ₂ -.

Further, according to a particularly preferred meaning, Z is connected to R ^{3 in} this way

is that the group of the subformula V ^Z \ yΛ has a meaning

R ³

selected from 1,3-pyrrolidinylene, 1,3-piperidinylene, 1,2,5,6-tetrahydropyridin-1, 3-ylene and 3-hydroxy-1,3-piperidinylene.

Preferably, the radical R ^{3 is} selected from the group methyl, ethyl, n-propyl, iso-propyl, 2-hydroxyethyl, 3-hydroxy-n-propyl or 2-hydroxy-1-methyl-ethyl, wherein in said groups , two or three H atoms may be replaced by F, or R ³ is selected from the group H, amino-C - ₃ -alkyl, C ₃ -alkyl-amino-C ₂ -3-alkyl or di- (Cι - _3- alkyl) -amino-C ₂ - ₃ -alkyl.

Particularly preferred meanings of the radical R ³ are H, methyl or ethyl, in particular H or methyl.

Preferred meanings of the radicals R ⁴ and / or R ⁵ are H, ₄ Cι- -alkyl, C _3-6 - cycloalkyl and C3-6-cycloalkyl-Cι _-3 alkyl, in particular H and Cι-4-alkyl. Preferred meanings of the group R ¹ are C ₆ -cycloalkyl, hydroxy, C ₁ . ₄ - alkoxy, amino, -C _-4 -alkyl-amino- and di- (-Cι- _4- alkyl) -amino-.

Preferred meanings of the group R ²⁰ are halogen, hydroxy, cyano, C ₁ -4-alkyl, C ₃ . ₇ -cycloalkyl and hydroxy-Cι- ₃ -alkyl. More preferably R ^{20 is} F, Cl, Br, I, OH, cyano, methyl, difluoromethyl, trifluoromethyl, ethyl, n-propyl, iso-propyl, methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, n-propoxy or iso-propoxy.

The group Y is preferably selected from the quantity of the bivalent cyclic groups 1, 2-cyclopropylene, 1,3-cyclobutylene, 1,3-cyclopentylene, 1,3-cyclopentenylene, 1,3- and 1,4-cyclohexylene, 1, 3-phenylene, 1, 4-phenylene, 1,3- and 1, 4-cyclohexenylene, 1, 4-cycloheptylene, 1,4-cycloheptenylene, 1,3-pyrrolidinylene, 1, 3-pyrrolinylene, 1, 3-pyrrolylene , 1, 4-piperidinylene, 1, 4-tetrahydropyridinylene, 1, 4-dihydropyridinylene, 2,4- and 2,5-pyridinylene or 1, 4-piperazinylene, wherein the above-mentioned 5-, 6- or 7-membered groups may be connected in a condensed form via a pair of adjacent, adjacent carbon atoms with a phenyl or pyridine ring, the abovementioned cyclic groups being mono- or polysubstituted by one or more carbon atoms with R ²⁰ , in the case of a phenyl group also additionally simply with Nitro, and / or to one or more N atoms with R ²¹ may be substituted, and wherein R ¹ with Y and / or R ³ with Y according to the manner indicated in the general definition v can be linked.

Very particularly preferred meanings of the group Y are selected from the group of cyclic structures consisting of:

wherein the cyclic groups one or two times, preferably simply, with R ²⁰ , preferably with halogen, CF ₃ , -C. _4- alkyl and / or Cι- _4- alkoxy, may be substituted. In addition, the group Y may also be connected to the radical R ^{1 in} such a way that

the group of the sub-formula ne meaning selected

the following sub-formulas

has.

Preferred meanings of group A are selected from the group of bivalent cyclic groups 1,2-cyclopropyls, 1,3-cyclobutylene, 1,3-cyclopentylene, 1,3-cyclopentenylene, 1,3- and 1,4-cyclohexylene, 1 , 3- and 1, 4-phenylene, 1, 3- and 1,4-cyclohexenylene, 1,4-cycloheptylene, 1,4-cycloheptenylene, 1,3-pyrrolidinylene, 1,3-pyrrolinylene, 1,3-pyrrolylene , 1, 4-piperidinylene, 1,4-tetrahydropyridinylene, 1,4-dihydropyridinylene, 2,4- and 2,5-pyridinylene, 1,4-piperazinylene, 7-azabicyclo [2.2.1] heptan-2, 7-diyl and 8-azabicyclo [3.2.1] octane-3,8-diyl, wherein the above-mentioned 5-, 6- or 7-membered groups have two common adjacent C atoms with a phenyl or pyridine -Ring condensed may be connected, and wherein the aforementioned cyclic groups one or more times to one or more C atoms with R ²⁰ , in the case of a phenyl group also additionally simply with nitro, and / or to one or more N atoms with R ²¹ can be substituted.

Very particularly preferred meanings of group A are selected from the group of cyclic structures consisting of:

wobei die cyclischen Gruppen ein- oder zweifach, vorzugsweise einfach, mit R²⁰, vorzugsweise mit Halogen, CF₃, Cι-₄-Alkyl und/oder Cι_-4-Alkoxy, substituiert sein können.

the cyclic groups being mono- or disubstituted, preferably monosubstituted, with R ^20, preferably with halogen, CF _3, Cι- ₄ alkyl and / or Cι _-4 alkoxy, may be substituted.

In the bivalent cyclic groups indicated for Y and / or A, the mirror-image forms, i. E. the forms in which the linkage with the adjacent groups, in the case of Y with X and Z and in the case of A with CO and W, reversed, comprises. For example, 1,4-cyclohexenylene means both

The bivalent cyclic groups previously given for the groups Y and A include all conceivable isomers. Hereinafter, meanings previously described as preferred are explained in more detail:

The meaning tetrahydropyridinylene includes the meanings 1, 2,3,4-tetrahydropyridine-1, 4 and -3,6-ylene, 1, 2,3,6-tetrahydropyridine-1, 4, 2, 5 and 3,6-ylene, 2,3,4,5-tetrahydropyridine-2,5- and -3,6-ylene. The preferred meaning here is 1, 2,3,6-tetrahydropyridin-1, 4-ylene.

The meaning Dihydropyridinylen includes the meanings 1,4- and 1, 2-dihydro-pyridin-1, 4-ylen and 1, 2-, 1, 4-, 1,6-, 2,3-, 2,5-, 3,4-, 4,5- and 5,6-dihydropyridine-2,5-ylene. The preferred meaning here is 1, 2-dihydropyridin-1, 4-ylene.

The groups A and / or B are preferably unsubstituted or monosubstituted or disubstituted by R ²⁰ , particularly preferably unsubstituted or simply substituted by R ²⁰ .

Preferred meanings of the group B are selected according to a first embodiment from the group Cι- ₆ alkyl, Cι- ₆ alkenyl, Cι. ₆ alkynyl, C ₃ . ₇ -

Cycloalkyl-C _{3 -3} alkyl, C ₃ . ₇ -Cycloalkenyl -C. _3- alkyl, C ₃ . ₇ -cycloalkyl-C _1-3 -alkenyl- be or C _3-7 cycloalkyl-Cι _-3 alkynyl, wherein one or more C atoms may be mono- or polysubstituted halogen and / or easily installed by hydroxy or cyano and / or cyclic groups substituted by one or more times with R ²⁰ can, and

W is a single bond, -O-, a C ₁ . Alkylene, C _2-4 alkenylene, C _2-4 alkynylene, Cι- ₄ alkyleneoxy, oxy-Cι- alkylene, _{alkylene-oxy-3} Cι- Cι _-3 alkylene, imino , N- (Cι _-3 - alkyl) -imino, lmino-C 4-alkylene, N- (Cι _-3 alkyl) -imino-Cι- alkylene, Cι- alkylene-imino- or C _-4- alkylene-N- (Cι _-3 -alkyl) -imino group, wherein one or two carbon atoms independently of one another with a hydroxy, ω-hydroxy-C _{3 -3} alkyl, ω- (Cι. _3- alkoxy) -Cι- ₃ alkyl and / or Cι- ₃ alkoxy radical and / or may be substituted by one or two identical or different d- ₄ alkyl radicals, and

k is 0 or 1, in particular 1 and

R ^{20 has} one of the meanings indicated.

In the abovementioned preferred meanings for B, k preferably has the value 1 and W preferably has the meaning single bond, imino or N- (C _1-3 -alkyl) -imino-, in particular single bond.

Particularly preferred here is the group B d-β-alkynyl, in particular C ₃ .. β-alk-1-ynyl, and / or the group W is a single bond, where k = 1.

Preferred meanings of group B according to a second embodiment are selected from the amount of the cyclic groups cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexanonyl, cyclohexenyl, phenyl, cycloheptyl, cycloheptenyl, aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, piperidinyl, tetrahydropyridinyl , Dihydropyridinyl, pyridinyl, azepanyl, piperazinyl, 1H-pyrazolyl, imidazolyl, triazolyl, tetrazolyl, morpholinyl, thiomorpholinyl, indolyl, isoindolyl, quinolinyl, benzoimidazolyl, isoquinolinyl, furanyl and thienyl, wherein the bond to the group W or optionally directly to the group A. via a C atom of the carbocyclic part or of the optionally fused phenyl or pyridine ring or via an N or C atom of the heterocyclic part, or B together with the via a double bond linked group W is selected from the group cyclopentylidene-methyl,

Cyclohexyliden-methyl and cyclohexanone-4-ylidene-methyl, and wherein the aforementioned cyclic groups one or more times to one or more carbon atoms with R ²⁰ , in the case of a phenyl group also additionally simply with nitro, and / or to an or may be substituted by several N atoms with R ²¹ .

Most preferably, the group B is phenyl which is monosubstituted, disubstituted or trisubstituted, preferably monosubstituted or disubstituted by R ²⁰ .

With the meanings given above for B, all conceivable isomers of the respective groups are included. Thus, in particular the following isomers are included: cyclopentene-1, 3 and 4-yl, cyclohexanone-4-yl, cyclohexene-1, 3 and 4-yl, cycloheptene-1, 3, 4 and 5 -yl, aziridin-1-yl, azetidin-1-yl, pyrrolidin-1-yl, pyrrolin-1-yl, pyrrol-1-yl, piperidine-1 and 4-yl, pyridine-2-, -3- and 4-yl, azeroman-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, quinoline-2, 3, 4 , 5-, 6-, 7- and 8-yl, isoquinoline-1, 3-, 4-, 5-, 6-, 7- and 8-yl, 1H-benzoimidazole-1, 2-, 4- , 5, 6 and 7-yl.

The meaning pyrazole includes the isomers 1 H, 3H and 4H-pyrazole. Pyrazolyl is preferably 1H-pyrazol-1-yl.

The meaning imidazole includes the isomers 1 H, 2H and 4H imidazole. A preferred meaning of imidazolyl is 1H-imidazol-1-yl.

The meaning tetrahydropyridine includes the isomers 1, 2,3,4-, 1, 2,3,6- and 2,3,4,5-tetrahydropyridine. Preferably, tetrahydropyridinyl 1, 2,3,4- and 1,2,3,6-tetrahydropyridin-1-yl.

The term dihydropyridine includes the isomers 1, 2, 1, 4, 2,3, 2,5 and 4,5 dihydropyridine. Preferably, dihydropyridinyl means 1, 2 and 1,4-dihydropyridine-1-yl.

The meaning triazole includes the isomers 1H-, 3H- and 4H- [1, 2,4] -triazole and 1 H, 2H and 4H [1,2,3] triazole. The meaning triazolyl therefore includes 1 H- [1,2,4] -triazole-1, 3- and 5-yl, 3H- [1, 2,4] -triazol-3-and 5-yl, 4H- [ 1,2,4] triazole-3, 4 and 5-yl, 1 H- [1,2,3] triazole-1, 4 and 5-yl, 2H- [1, 2,3 ] Triazole-2-, 4- and 5-yl and 4H- [1,2,3] triazole-4 and 5-yl.

The term tetrazole includes the isomers 1H, 2H and 5H-tetrazole. The meaning tetrazolyl therefore includes 1 H-tetrazol-1 - and 5-yl, 2H-tetrazol-2 and 5-yl and 5H-tetrazol-5-yl.

The meaning indole includes the isomers 1 H and 3H indole. The term indolyl is preferably 1H-indol-1-yl.

The meaning isoindole includes the isomers 1 H and 2H isoindole. The term isoindolyl is preferably 2H-isoindol-2-yl.

In general, the bond to one of the abovementioned heterocyclic groups, in particular to a pyrazolyl, imidazolyl, tetrahydropyridinyl, dihydropyridinyl, triazolyl, tetrazolyl, indolyl or isoindolyl group, via a C atom or, if appropriate, an N- Atom of an imine function.

The group B is preferably unsubstituted, monosubstituted, disubstituted or trisubstituted by R ²⁰ . B is particularly preferably monosubstituted or disubstituted by R ²⁰ . In the case where B is a substituted six-membered ring, it is preferably one

A substituent in para position to the bond of the group "

The index k can take the values 0 or 1. In the preferred case k = 1, the bridge W has the given meanings, preferably the meanings single bond, -CH ₂ - or -CH =. Preferred meanings of the sub-formula -AW-B are selected from the structures listed in the list below, wherein V is a C or N atom, preferably a C atom, and the cyclic groups listed one or more times to one or more C- Atoms with R ²⁰ and in the case of phenyl or phenylene groups may also additionally be substituted by nitro:

Very particular preference is given to the compounds of the formula I in which k = 1 and W denote a single bond.

The index k can also assume the value 0. According to a first sub-variant thereof, the group A is connected to the group B via a common carbon atom to form a spirocyclic ring system, wherein the group A is a saturated 5- to 7-membered and the group B is a saturated 4- to 7-membered carbo- or heterocyclic group, and wherein the heterocyclic groups each have an N, O or S atom, and wherein a 5- to 7-membered group B via two adjacent carbon atoms, a phenyl or pyridine ring may be fused, and wherein the aforementioned cyclic groups one or more times to one or more C atoms with R ²⁰ , in the case of a fused phenyl ring also additionally simply with nitro, and / or to one or more N atoms with R ²¹ may be substituted.

Preferred meanings of the sub-formula -AWB according to these second sub-variants are selected from the structures listed in the table below, wherein the cyclic groups listed one or more times to one or more C atoms with R ²⁰ and in the case of the phenyl ring also additionally with nitro may be substituted:

According to a second sub-variant to the case k = 0, the group B is connected to the group A via two common adjacent atoms to form a fused, bicyclic saturated, unsaturated or aromatic, 8 to 12 membered ring system having one or more same or may have different heteroatoms selected from N, O and / or S, and wherein the bicyclic ring system one or more times to one or more C atoms with R ²⁰ , in the case of a fused phenyl ring also additionally simply with nitro, and / or at one or more N atoms may be substituted with R ²¹ .

Preferred meanings of the sub-formula -AWB according to these first sub-variants are selected from the structures listed in the table below, wherein the cyclic groups listed one or more times to one or more C atoms with R ²⁰ and in the case of the phenyl ring also additionally simply with nitro may be substituted.

Those compounds according to the invention are preferred in which one or more of the groups, radicals, substituents and / or indices has one of the meanings given above as being preferred. Preferred meanings of the substituent R ²⁰ are selected from the group consisting of fluorine, chlorine, bromine, CF ₃ , Cι- alkyl, Cι- alkoxy

In particular, those compounds according to the invention are preferred in which

Y, A are independently selected from the group of bivalent cyclic groups 1, 4-phenylene, 1,4-cyclohexylene, 1,4-cyclohexenylene, 1,4-piperidinylene, 1,2,3,6-tetrahydropyridine 1,4-ylene,

2,5-pyridinylene and 1, 4-piperazinylene, wherein A may also be connected to R ³ according to claim 3, and wherein the aforementioned cyclic groups one or more times to one or more C atoms with R ²⁰ , in the case of Phenyl group can also be additionally substituted simply with nitro, and / or to one or more N atoms with R ²¹ ,

B phenyl or cyclohexyl, where said groups may be monosubstituted or polysubstituted by R ²⁰ and / or the phenyl ring may additionally be substituted by nitro, R ^{20 being} those specified in claim 1

Owns meanings, and

k has the value 1,

W is a single bond, -CH ₂ - or -CH =, and

Z is -CH ₂ -CH ₂ -, -CH ₂ -CH (CH ₃ ) -, -CH ₂ -C (CH ₃ ) ₂ -, -CH (CH ₃ ) -CH ₂ -,

-C (CH ₃ ) ₂ -CH ₂ - or -CH ₂ -O- means or

is so connected to R ³ that the group of the sub-formula

1 ,3-Pyrrolidinylen und 1 ,3-Piperidinylen besitzt.of formula I selected from meaning

1, 3-pyrrolidinylene and 1, 3-piperidinylene has.

Particularly preferred compounds according to the invention are listed in the following group of formulas 1.1 to 1.14:

worin

wherein

U, V independently of one another C or N,

R ₅ 23, _D R24 independently of one another are H, F, methyl, trifluoromethyl, ethyl, isopropyl or n-propyl,

wherein in the formulas 1.1 to I.6 R 5 ≤4 be so connected to R

eine Bedeutung ausgewählt aus 1 ,3-Pyrrolidinylen und 1 ,3- Piperidinylen besitzt, undthat can be the group of the subformula

has a meaning selected from 1, 3-pyrrolidinylene and 1, 3-piperidinylene, and

H fü'trv R D 0 angegebenen Bedeutungen oder im Falle einer Phenylgruppe auch einfach Nitro, wobei mehrfach vorkommende Reste R²⁵, R²⁶, R²⁷ gleiche oder verschiedene Bedeutungen aufweisen können, undR) 26, Q R2 ui innanhbhhäSnnΛgiiing i vmonnnelinnannnrdlΛerr

H for RD 0 given meanings or in the case of a phenyl group also simply nitro, where multiple occurring radicals R ²⁵ , R ²⁶ , R ^{27 may have the} same or different meanings, and

0, 1, 2, 3 or 4 is and

m, n independently of one another denote 0, 1 or 2.

Very particular preference is given to compounds according to the above formulas 1.1, 1.2, I.8, 1.10 and 1.12. In particular, very particularly preferred compounds can be described by the following formulas

where the radicals and substituents have the meanings given above and below.

Furthermore, according to the invention are compounds of the following sub-formula

preferably, in which

B is selected from the group Ci-e-alkyl, _-6- alkenyl, _-6- alkynyl, C _3-7 - cycloalkyl-C _{3 -3} alkyl, C ₃ -7-cycloalkenyl-C. ₃ -alkyl-, C _3-7 -cycloalkyl-Cι _-3 - alkenyl or C ₃ - ₇ -cycloalkyl-Cι _-3 -alkynyl-, wherein one or more carbon atoms one or more times with halogen and / or simple with hydroxy or cyano and / or cyclic groups may be monosubstituted or polysubstituted by R ²⁰ , and

W is a single bond, -O-, a d- _4- alkylene, C _2- alkenylene, C ₂ - ₄ -

Alkynylene, Cι _-4 -alkyleneoxy, oxy-Cι- _4- alkylene, C ₁ . ₃ -alkylene-oxy-d. ₃ - alkylene, imino, N- (Cι _-3 alkyl) imino, lmino-d- _4- alkylene, N- (-C ₃ alkyl) - imino-Cι-4-alkylene, -C _-4- alkylene-imino or Cι _-4- alkylene-N- (Cι- _3- alkyl) - imino group, wherein one or two carbon atoms independently each other with a hydroxy, co-hydroxy-Cι- ₃ -alkyl-, ω- (-C ₃ -alkoxy) - -C. ₃ alkyl and / or Cι _-3 alkoxy-radical and / or with one or two identical or different Cι-4-alkyl radicals may be substituted, and

k is 0 or 1.

Furthermore are preferred according to this embodiment, those compounds in which the group B Cι _-6 alkyl, Cι- ₆ alkynyl, C _3- 7 cycloalkyl-Cι- ₃ alkyl or C ₃ - ₇ - cycloalkyl-Cι-3 -alkynyl-, in which one or more carbon atoms may be monosubstituted or polysubstituted by halogen and / or simply substituted by hydroxy or cyano and / or cyclic groups mono- or polysubstituted by R ²⁰ , and / or

W is a single bond, -O-, imino or N- (Cι _-3 alkyl) -imino- means, where one or two C atoms independently of one another with a hydroxy, alkyl ω-hydroxy-Cι- _3, ω- (-C _1-3 alkoxy) -Cι- ₃ alkyl and / or Cι- alkoxy radical and / or may be substituted with one or two identical or different Cι- ₄ alkyl radicals and K = 1 ,

Most particularly preferred meanings of the group -WB according to this embodiment are selected from the group consisting of Cι _-8 alkyl, - C≡Cde-alkyl, -CH = CH-Cι _-6 alkyl, -0-Cι. ₆ -Alkyi, -NH (d _-6 alkyl), and -N (Cι. ₆ - alkyl) (Cι _-3 alkyl), in particular selected from the group consisting of C _{3. 8} - alkyl, -C≡C-C ₃ - ₆ alkyl, -CH = CH-C ₃ -6-alkyl, -0-C. _{3 6} alkyl, -NH (C _{3 6} alkyl.), And -N (C ₃ - ₆ alkyl) (Cι _-3 alkyl).

Those of the compounds according to the invention described above as preferred, in particular of the sub-formulas 1.1 to 1.15, are particularly preferred in which the radicals R ¹ , R ² , R ³ , L ¹ , L ² , L ³ and / or group X is one of the respective preferably have given meanings.

In particular, those compounds according to the invention are particularly preferred in which X is selected from -CH ₂ -, -CH (CH ₃ ) - or -C (CH ₃ ) ₂ -. Furthermore, those of the compounds of sub-formulas 1.1 to 1.15 are particularly preferred in which a) the group U is an N atom and the group V is a C atom, or b) the group U is a C atom and the group V is an N atom Atom, or c) both groups U and V each represent a C atom.

In particularly preferred compounds according to the invention, the substituents R ²⁵ , R ²⁶ , R ²⁷ independently of one another have a meaning selected from F, Cl, Br, I, OH, cyano, methyl, difluoromethyl, trifluoromethyl, ethyl, n-propyl, isopropyl, Methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, n-propoxy or iso-propoxy, in the case of the substitution of a phenyl group also simply nitro, where multiple occurring radicals R ²⁵ , R ²⁶ , R ^{27 may have the} same or different meanings, and j 0, 1 or 2, and m, n are independently 0 or 1.

Preferred meanings of the radicals R ⁶ , R ⁷ , R ⁸ and / or R ⁹ in the compounds according to the invention described as being preferred are independently H, methyl, trifluoromethyl, ethyl, iso-propyl or n-propyl, in the case of R ⁶ , R ⁷ also F.

Particularly preferred single compounds are selected from the group

(1) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3-quinazolin-4-one

(2) 3- [2- (4-Pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7-p-tolyl-3H-quinazolin-4-one

(3) 3- [2- (4-Pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7- (4-trifluoromethyl-phenyl-SH-quinazolinone) -one

(4) 7- (4-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethoxy-SH-quinazolinone] -one

(5) 7- (3,4-Dichloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3-quinazolin-4-one

(6) 7- (4-fluoro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) - ethyl] -3H-quinazolin-4-one

7) 7- (4-ethylphenyl) -3- [2- (4-pyrrolidin-1-ylmethylphenyl) ethyl] -3H-quinazolin-4-one

8) 2-Methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7- (4-trifluoromethylphenyl) -3H-quinazolin-4-one

9) 2-Methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7-p-tolyl-3H-quinazolin-4-one

10) 7- (4-Chloro-phenyl) -2-methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

11) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -1H-quinazoline-2,4-dione

12) 7- (4-Chloro-phenyl) -3- {2- [4 - ((S) -2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -3- / -quinazoline-4 on

13) 7- (4-Chloro-phenyl) -3- [2- (4-dimethylaminomethyl-phenyl) -ethyl] -3H-quinazolin-4-one

14) 7- (4-Chloro-phenyl) -3- [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

15) 7- (4-Chloro-phenyl) -3- [2- (4-morpholin-4-yl-methylphenyl) -ethyl] -3 / -quinazolin-4-one

16) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-benzo [o] [1,2,3] triazin-4-one

17) 5- (4-fluoro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -isoindole-1,3-dione

18) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

19) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

20) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide (21) 4'-Methoxy-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

(22) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amide

(23) 4- (4-Chloro-phenyl) -cyclohexanecarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(24) 4-Methylphenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(25) 4- (4-Chloro-phenyl) -3,6-dihydro-2H-pyridine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(26) 4- (4-Chloro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(27) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide

(28) 4'-Chloro-biphenyl-4-carboxylic acid (4-pyrrolidin-1-ylmethyl-benzyloxy) -amide

(29) 4-Cyclohexyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(30) 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(31) 7- (4-Chloro-phenyl) -3- {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -3H-quinazolin-4-one

(32) 4'-Chloro-biphenyl-4-carboxylic acid {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -amide

(33) 7- (3-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

(34) 4- (4-Oxo-cyclohexyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (35) 4-Cyclohexyl-1-cyclohexylcarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(36) 4-Benzyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(37) 4-Cyclohexyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(38) 4- (4-Chloro-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(39) 4- (4-Fluoro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(40) 4- (4-Methoxy-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(41) 4-phenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(42) (4'-Chlorobiphenyl-4-yl) - [3- (4-pyrrolidin-1-ylmethyl-phenyl) -piperidin-1-yl] -methanone

(43) 4'-Chloro-biphenyl-4-carboxylic acid [2-methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide

(44) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-cyclohexyl) -ethyl] -amide

(45) 4-Benzyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(46) 4- (4-Oxo-cyclohexylidenemethyl) - / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(47) 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-fluoro-4-pyrrolidin-1-yl-methyl-1-phenyl) -ethyl] -amide

(48) 5- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2,3-dihydroisoindole-1-one (49) 4-pi-pyridine-1-yl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(50) 7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [d] [ 1, 2,3] triazin-4-one

(51) 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

(52) 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3W-benzo [c /] [1,2,3] triazin-4-one

(53) 7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3r7 ^, -quinazolin-4 on

(54) 7- (4-Chloro-phenyl) -3- (2- {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl-ethyl-Sy-quinazolin-1-one

(55) 6- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2H-isoquinolin-1-one

(56) 4'-Chlorobiphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(57) 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(58) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethyl} -amide

(59) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (4-acetylpiperazin-1-ylmethyl) -phenyl] -ethyl} -amide

(60) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (2-azabicyclo [2.2.1] hept-5-en-2-ylmethyl) -phenyl] -ethyl} -amide

(61) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (1,3-dihydro-isoindol-2-ylmethyl) -phenyl] -ethyl} -amide

(62) 4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(diisopropylamino) -methyl] -phenyl} -ethyl) -amide O 2004,024702

(63) 4'-Chlorobiphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

(64) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-dimethylaminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

(65) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (3-dimethylamino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

(66) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(67) 4-Pent-1-ynyl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(68) 4'-Chloro-biphenyl-4-carboxylic acid [2- (6-pyrrolidin-1-ylmethyl-pyridin-3-yl) -ethyl] -amide

(69) 4'-Chlorobiphenyl-4-carboxylic acid [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -amide

(70) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-nitro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(71) 2 ', 4'-Dichlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(72) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (3-amino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

(73) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-aminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

(74) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methyl-2,6-diazo-spiro [3,4] oct-6-ylmethyl) -phenyl] -ethyl} -amide

(75) 4'-Chloro-biphenyl-4-carboxylic acid [2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -ethyl] -amide

(76) 4'-Chlorobiphenyl-4-carboxylic acid [2- (3-ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (77) 4'-Bromo-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

(78) 4- (5-Chloro-thiophen-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

(79) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(80) 4'-Bromo-3-fluoro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

(81) 4'-Chloro-2-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(82) 4'-Ethyl-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(83) [1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-2-ylmethyl] -carbamic acid tert-butyl ester

(84) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpiperidin-1-ylmethyl) -phenyl] -ethyl} -amide

(85) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

(86) 4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(cyclopropylmethyl-amino) -methyl] -phenyl} -ethyl) -amide

(87) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3,4-dihydro-1H-isoquinolin-2-ylmethyl) -phenyl] -ethyl} -amide

(88) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4 - {[(2-hydroxy-ethyl) -methyl-amino] -methyl} -phenyl) -ethyl] -amide

(89) [1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester

(90) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2,6-dimethyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide , "". "" O 2004/02470 59/334

(91) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4-azetidin-1-ylmethyl-phenyl) -ethyl] -amide

(92) 3,4'-dichlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(93) 4'-Fluorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(94) 4'-Chloro-3-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(95) 2'-Fluoro-4'-chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(96) 5- (4-Chloro-phenyl) -pyridine-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(97) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

(98) 4'-Bromo-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

(99) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -amide

Very particular preference is given to the abovementioned individual compounds of the formulas (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23 ), (24), (25), (25), (26), (27), (28), (29), (30), (47) and (50) to (99).

In the following, terms which are used previously and hereinafter for the description of the compounds according to the invention are defined in more detail.

The term halogen denotes an atom selected from the group consisting of F, Cl, Br and I. The name C _n- alkyl, wherein n has a value of 3 to 8, means a saturated, branched or unbranched hydrocarbon group having 1 to n carbon atoms. Examples of such groups include methyl, ethyl, n-propyl, iso-propyl, butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl, n-hexyl, iso-hexyl, etc.

The term Cι- may have _n -alkylene, where n is from 1 to 8, denotes a saturated, branched or unbranched hydrocarbon bridge with 1 to n C atoms. Examples of such groups include methylene (-CH ₂ -), ethylene (-CH ₂ -CH ₂ -), 1-methyl-ethylene (-CH (CH ₃ ) -CH ₂ -), 1, 1-dimethyl-ethylene (- C (CH ₃ ) ₂ -CH ₂ -), n -prop-1,3-ylene (-CH ₂ -CH ₂ -CH ₂ -), 1-methylprop-1, 3-ylene (--CH (CH ₃ ) -CH ₂ -CH ₂ -), 2-methylprop-1, 3-ylene (-CH ₂ -CH (CH ₃ ) -CH ₂ -), etc., as well as the corresponding mirror-image forms.

The term C ₂ - _n alkenyl, wherein n has a value of 3 to 6, denotes a branched or unbranched hydrocarbon group having 2 to n C atoms and at least one C = C double bond. Examples of such groups include vinyl, 1-propenyl, 2-propenyl, iso-propenyl, 1,3-butadienyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 1-pentenyl, 2- Pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-2-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 2,4-hexadienyl, 5-hexenyl, etc.

The term C 1- _n -alkoxy denotes a -O-C 1 _-n- alkyl group in which C 1- _n -alkyl is as defined above. Examples of such groups include methoxy, ethoxy, n-propoxy, iso -propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, iso-pentoxy, neo-pentoxy, tert-pentoxy, n- Hexoxy, iso-hexoxy etc.

The term C 1 _-n- alkylthio denotes an -S-C 1 _-n -alkyl group, in which C 1- _n -alkyl is as defined above. Examples of such groups include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, isopentylthio, neo-pentylthio, tert-pentylthio, n-butylthio Hexylthio, iso-hexylthio, etc. The term Ci-n-alkylcarbonyl denotes a -C (= O) -Cι- _n- alkyl group, wherein Ci. _n- alkyl is as defined above. Examples of such groups include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, iso-propylcarbonyl, n-butylcarbonyl, iso-butylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, iso-pentylcarbonyl, neo-pentylcarbonyl, tert-pentylcarbonyl, n-butyl Hexylcarbonyl, isohexylcarbonyl, etc.

The term C _3-n -cycloalkyl denotes a saturated mono-, bi-, tri- or spirocarbocyclic group having 3 to n C atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclododecyl, bicyclo [3.2.1.] Octyl, spiro [4.5] decyl, norpinyl, norbornyl, norcaryl, adamantyl, etc.

The term C ₃ . _n -cycloalkylcarbonyl denotes a -C (= O) -C ₃ . _n -cycloalkyl group, wherein C _3-n -cycloalkyl is as defined above.

The term aryl refers to a carbocyclic aromatic ring system such as phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl, etc.

The term heteroaryl used in this application denotes a heterocyclic, aromatic ring system which, in addition to at least one C atom, comprises one or more heteroatoms selected from N, O and / or S. Examples of such groups are furanyl, thiophenyl (thienyl), pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,3,5-triazolyl,

Pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1, 2,3-triazinyl, 1,2,4-triazinyl, 1, 3,5-triazinyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1, 3,4-oxadiazolyl, 1, 2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1, 2,5-thiadiazolyl, 1, 3,4-thiadiazolyl, tetrazolyl, Thiadiazinyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl (thianaphthenyl), indazolyl, benzimidazolyl, benzthiazolyl,

Benzisothiazolyl, benzoxazolyl, benzisoxazolyl, purinyl, quinazolinyl, quinolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, azepinyl, diazepinyl, acridinyl, etc. The term heteroaryl also includes the partially hydrogenated heterocyclic aromatic ring systems, in particular the listed above. Examples of such partially hydrogenated ring systems are 2,3-dihydrobenzofuranyl, pyrolinyl, pyrazolinyl, indolinyl, oxazolidinyl, oxazolinyl, oxazepinyl, etc.

Terms such as aryl-Cι _-n alkyl, _heteroaryl-n Cι- alkyl, etc. denote Ci- _n -alkyl, which is substituted with an aryl or heteroaryl group as defined above. Some of the previously mentioned terms can be used multiple times in the definition of a formula or group and each independently have one of the meanings given.

The term "unsaturated carbocyclic group" or "unsaturated heterocyclic group", as used in particular in the definition of the group Cy, in addition to the fully unsaturated groups, also includes the corresponding, only partially unsaturated groups, especially mono- and diunsaturated groups.

The term "optionally substituted" used in this application means that the group so designated is either unsubstituted or monosubstituted or polysubstituted by the specified substituents. If the group in question is substituted several times, the substituents may be the same or different.

The radicals and substituents described above may be mono- or polysubstituted by fluorine in the manner described. Preferred fluorinated alkyl radicals are fluoromethyl, difluoromethyl and trifluoromethyl. Preferred fluorinated alkoxy radicals are fluoromethoxy, difluoromethoxy and trifluoromethoxy. Preferred fluorinated alkylsulfinyl and alkylsulfonyl groups are trifluoromethylsulfinyl and trifluoromethyl isulfonyl.

The compounds of general formula I according to the invention may have acid groups, mainly carboxyl groups, and / or basic groups such as amino functions. Compounds of the general formula I can therefore be used as internal salts, as salts with pharmaceutically usable inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, Sulfonic acid or organic acids (such as maleic acid, fumaric acid, citric acid, tartaric acid or acetic acid) or as salts with pharmaceutically usable bases such as alkali or alkaline earth metal hydroxides or carbonates, zinc or ammonium hydroxides or organic amines such as diethylamine, triethylamine, triethanolamine, inter alia.

The compounds according to the invention can be obtained using synthesis methods known in principle. The compounds are preferably obtained by the preparation process described above and explained in more detail below.

The erfindunsgsgemäße manufacturing method for the first group of preferred embodiments, ie those compounds in which the group A and the radical R ^{3 is} not directly connected to each other, basically distinguishes two applications.

The first case covers those compounds of the formula I in which the group A represents a nitrogen-heterocyclic group which is bonded via a nitrogen atom to the carboxylic acid amide group and may also have one or more heteroatoms selected from N, O and S in addition to the nitrogen atom , The reaction of the amine of formula 1-1 with the secondary amine of formula I-2 is illustrated in the following general reaction scheme:

Reaction Scheme 1:

Preferably, the amine compound of the formula 1-1 is first reacted with CDT (1,1'-carbonyldi (1, 2,4-triazole)) in a solvent or solvent mixture and then the reaction mixture with the amine compound of the formula I. -2, wherein the at least one base is added to the reaction mixture before and / or after the reaction of the amine compound with CDT. Advantageously, in this case, the amine compound of formula 1-1 with CDT in a temperature range from -20 ° C to 20 ° C and then this reaction mixture with the amine compound of formula I-2 in a temperature range of 40 ° C to 100 ° C in a molar ratio of the amine compound of formula 1-1: amine compound of formula I-2: CDT: base of 1 + 0.25: 1 ± 0.25: 1 ± 0.25: 3 ± 1, 5 implemented. Preferred bases are nitrogen bases, in particular tert. Amines, such as triethylamine used.

The amine compound of the formula I-2 may be a saturated N-heterocyclic compound, such as, for example, a piperazine derivative according to the following Reaction Scheme 2. Reaction scheme 2

The second case of the production process comprises the other compounds of formula I not covered by case 1, in which group A is not directly linked to R ³ . The reaction of the carboxylic acid compound of formula I-3 with TBTU (2- (1H-benzotriazol-1-yl) -1,3,3,3-tetramethyluronium tetrafluoroborate) and the amine compound of formula 1-1 in one Solvent or solvent mixture in the presence of at least one base is shown in Reaction Scheme 3.

Reaction Scheme 3:

Vorzugsweise wird hierbei die Carbonsäure-Verbindung der Formel 1-3 mit TBTU in einem Lösungsmittel oder Lösungsmittelgemisch umgesetzt und anschließend die Reaktionsmischung mit der Amin-Verbindung der Formel 1-1 weiter umgesetzt, wobei die mindestens eine Base vor und/oder nach der Umsetzung der Carbonsäure-Verbindung mit TBTU der Reaktionsmischung hinzugegeben wird. Anstatt einer Carbonsäure können auch die entsprechenden aktivierten Carbonsäure-Derivate, wie beispielsweise Ester, ortho-Ester, Carbonsäurechloride oder Anhydride, zum Einsatz kommen. Vorzugsweise wird als Base eine Stickstoff-Base, insbesondere ein tert.-Amin, wie beispielsweise Triethylamin eingesetzt. Vorteilhaft wird die Carbonsäure- Verbindung der Formel I-3 mit TBTU sowie anschließend diese Reaktionsmischung mit der Amin-Verbindung der Formel 1-1 in einem Temperaturbereich von 0°C bis 60°C in einem molaren Verhältnis der Carbonsäure-Verbindung der Formel I-3 : Amin-Verbindung der Formel 1-1 : TBTU : Base von 1 + 0,25 : 1 ± 0,25 : 1 ± 0,25 : 1 bis 4 eingesetzt.

Preferably, in this case, the carboxylic acid compound of formula 1-3 is reacted with TBTU in a solvent or solvent mixture and then the reaction mixture further reacted with the amine compound of formula 1-1, wherein the at least one base before and / or after the reaction of Carboxylic acid compound with TBTU is added to the reaction mixture. Instead of a carboxylic acid and the corresponding activated carboxylic acid derivatives, such as esters, ortho-esters, carboxylic acid chlorides or anhydrides, are used. The base used is preferably a nitrogen base, in particular a tertiary amine, for example triethylamine. Advantageously, the carboxylic acid compound of formula I-3 with TBTU and then this reaction mixture with the amine compound of formula 1-1 in a temperature range from 0 ° C to 60 ° C in a molar ratio of the carboxylic acid compound of formula I 3: Amine compound of the formula 1-1: TBTU: base of 1 + 0.25: 1 ± 0.25: 1 ± 0.25: 1 to 4 used.

The starting compound of the formula I-3 is obtainable according to methods known to the person skilled in the art. Thus, biaryl compounds can be obtained by Suzuki coupling, for example starting from p-bromoarylcarboxylic acid derivatives and aryl boronic acid derivatives in the presence of Pd [0] catalysts.

The erfindunsgsgemäße manufacturing method to the second group of preferred embodiments, ie those compounds in which the group A and the radical R ³ are connected to each other, according to the meanings purple to lllg the group Q seven applications.

According to the first case in which Q is -CR ⁶ R ⁷ - (IIIa), an amine compound of formula Ia 1 is reacted with an o-bromomethyl-benzoic acid ester derivative of formula Ia 2, which is shown in reaction scheme 4 below , in which the sake of clarity, the substituents L ¹ , L ² , L ^{3 have been} omitted on the phenyl ring, is illustrated. Reaction Scheme 4:

la.1 la.2

la.1 la.2

K _g CO _g

CH ₃ CN

Preferably, in this case, the o-bromomethyl-benzoic acid derivative of the formula Ia.2 is reacted with the amine compound of the formula Ia in a solvent or solvent mixture, at least one base being added. Instead of an o-bromomethylbenzoic acid ester derivative of the formula Ia.2, other corresponding o-benzylbenzoic acid ester derivatives (iodine or mesylate instead of bromine) can also be used. Preferably, potassium carbonate or cesium carbonate is used as the base, and tert. Amine bases such as triethylamine. Advantageously, the o-bromomethyl-benzoic acid derivative of formula la.2 in acetonitrile with the amine of formula la.1 and with potassium carbonate as the base in a temperature range of 40-80 ° C in a molar ratio of the o-bromomethyl-benzoic acid derivative of Formula la.2: Amine of formula la.1: potassium carbonate 1 + 0.25: 1 + 0.25: 3 + 0.50 used.

According to the second case, in which Q represents -CR ⁶ = R ⁷ - (IIIb), an isoquinolinone derivative of the formula Ib.3 is reacted with an electrophilic compound of the formula Formula lb.4 converted to an isoquinoline derivative of formula Ib.5, which is further derivatized by known methods to the compound of formula I. The isoquinolinone derivative of formula lb.3 is obtainable from cinnamic acid derivatives of the formula lb.1 by reaction with (EtO) ₂ P (0) N. ₃ The synthesis of the basic body was described by M. Becker et al. in Bioorganic & Medicinal Chemistry Letters 9 (1999), 2753-2758. The reaction is illustrated in the following Reaction Scheme 5, in which, for reasons of clarity, the substituents L ¹ , L ² , L ³ on the phenyl ring have been omitted.

Reaction Scheme 5:

Eine Verbindung der Formel lb.2 wird vorteilhaft durch die nachfolgend beschriebene Reaktionssequenz erhalten. Das Acrylsäurederivat lb.1 wird zunächst durch Einwirkung von Chlorierungsmitteln wie Thionylchlorid, Phosphorpentachlorid oder Oxalylchlorid ohne oder gegebenenfalls in einem inerten Lösungsmittel wie Dichlormethan zum Säurechlorid bei Temperaturen zwischen 0 °C und 80 °C umgesetzt. Dieses wird durch Einwirkung von Natriumazid in einem Lösungsmittel oder Lösungsmittelgemisch in das Acrylsäureazidderivat überführt. Als Lösungsmittel können zum Beispiel Dioxan, Tetrahydrofuran oder Wasser dienen. Vorzugsweise erfolgt die Synthese des Isocyanatderivates lb.2 direkt durch Einwirkung von

A compound of the formula Ib 2 is advantageously obtained by the reaction sequence described below. The acrylic acid derivative Ib.1 is first reacted by the action of chlorinating agents such as thionyl chloride, phosphorus pentachloride or oxalyl chloride without or optionally in an inert solvent such as dichloromethane to the acid chloride at temperatures between 0 ° C and 80 ° C. This is converted to the acrylic acid azide derivative by the action of sodium azide in a solvent or solvent mixture. As a solvent, for example, dioxane, tetrahydrofuran or water can serve. Preferably, the synthesis of the isocyanate derivative lb.2 is carried out directly by the action of

Phosphorsäurediphenylesterazid on the acrylic acid derivative lb.1 in the presence of a base in a solvent at temperatures between 0 ° C and 150 ° C. Suitable solvents are, for example, toluene or dioxane. Tertiary amines such as triethylamine can be used as bases. The above reactions have reaction times between one and twelve hours. Advantageously, the reaction of the acrylic acid derivative lb.1 with

Phosphoric acid diphenyl ester azide and triethylamine in a molar ratio of 1 + 0.25: 1 + 0.25: 1 + 0.25 in toluene as solvent. The isocyanate derivative Ib.2 is heated in a solvent, optionally in the presence of a base such as tributylamine, to form the isoquinolone derivative of the formula Ib.3. The reaction preferably proceeds in diphenyl ether in the region of the boiling point. Heating sources are oil, metal or microwave. The reaction of the isoquinolone derivative of the formula Ib 3 with the mesylate derivative of the formula Ib 4 to the isoquinolone derivative of the formula Ib 5 is carried out in a solvent in the presence of a base at temperatures between 0 ° C. and 150 ° C. Advantageously, the reaction of the isoquinolone derivative Ib.3 with the mesylate derivative of the formula Ib.4 and sodium hydride proceeds in a molar ratio of 1 + 0.25: 1 + 0.25: 1 + 0.25 in DMF as solvent.

The isoquinolone derivative of formula Ib.5 is first reacted in a solvent in the presence of an acid to convert the acetal to the corresponding aldehyde. This is in the presence of a hydride, an amine and an acid in a solvent in one Compound of formula Ib transferred. Examples of suitable hydride carriers are sodium triacetoxyborohydride, sodium borohydride and sodium cyanoborohydride. Advantageously, the reaction of the aldehyde released from the isoquinolone derivative Ib.5, with an amine and sodium cyanoborohydride in a molar ratio of 1 + 0.25: 1 + 0.25: 0.8 + 0.25 in methanol and acetic acid at temperatures around 20 ° C.

The synthesis of isoquinolines of the formula Ib, including the starting compounds and subsequent derivatization to the amine, is illustrated by the following synthesis scheme of a specific compound, where the synthesis of the starting material 1 can be found in Scheme 6 below for the preparation of phthalazinones (Scheme 8).

Reaction scheme 6:

According to the third case, in which Q denotes -N = CR ⁸ - (IIIc), a phthalazinone derivative of the formula Ic.4 is reacted with an electrophilic compound of the formula Ic.5 to give a phthalazinone derivative of the formula Ic.6, which is further derivatized by known methods to the compound of formula Ic. The phthalazinone derivative of the formula Ic.4 for R ⁸ = hydrogen is starting from the phenyloxazole derivative of the formula Ic.1 by acylation to an o-oxazolyl-benzaldehyde derivative of the formula Ic.2 and subsequent cyclization to a 3-hydroxy -3H-isobenzofuran-1-one derivative of formula lc.3 available. The synthesis of the body was described by M. Napoletano et al., Bioorganic & Medicinal Chemistry Letters 12 (2002), 5-8. The conversion to compounds The general formula Ic is illustrated in the following Reaction Scheme 7, in which, for the sake of clarity, the substituents L ¹ , L ² L ³ on the phenyl ring have been omitted.

Reaction scheme 7:

H ₂ S0 ₄

Obige Reaktionssequenz wird im nachfolgender detaillierter beschrieben: Das Oxazolinderivat lc.1 wird durch ein geeignetes metallorganisches Reagenz metalliert und anschließend mit einem Formaldehydäquivalent wie beispielsweise Dimethylformamid oder einem Ameisensäureorthoester bei Temperaturen zwischen -70 °C und 20 °C, vorzugsweise bei Temperaturen zwischen -20 °C und 0 °C zu einer Verbindung der Formel lc.2 umgesetzt. Als Lösungsmittel können zum Beispiel Dioxan, Tetrahydrofuran oder Diethylether dienen. Durch Einwirkung von wässriger Schwefelsäure in einem Lösungsmittel wie beispielsweise Ethanol bei einer Temperatur in der Nähe des Siedepunktes des Lösungsmittels oder Lösungsmittelgemisches in einem Zeitraum von einer bis 24 Stunden ist eine Verbindung der allgemeinen Formel lc.3 zugänglich. Das Phthalazinonderivat der Formel lc.4 kann man durch Umsetzung einer Verbindung der Formel lc.3 mit Hydrazin in Essigsäure und gegebenenfalls in einem Lösungsmittel bei Temperaturen zwischen 20 und 120 Grad Celsius erhalten. Der Syntheseweg zum Phthalazinonderivat der Formel Ic erfolgt analog der Umsetzungen wie für die Synthese einer Verbindung der allgemeinen Formel Ib beschrieben.

The above reaction sequence is described in more detail below: The oxazoline derivative lc.1 is metallated by a suitable organometallic reagent and then with a formaldehyde equivalent such as dimethylformamide or a formic acid orthoester at temperatures between -70 ° C and 20 ° C, preferably at temperatures between -20 ° C and 0 ° C to give a compound of formula lc.2 implemented. As a solvent, for example, dioxane, tetrahydrofuran or diethyl ether can serve. By the action of aqueous sulfuric acid in a solvent such as ethanol at a temperature near the boiling point of the solvent or solvent mixture in a period of one to 24 hours, a compound of the general formula Ic.3 is available. The phthalazinone derivative of formula Ic.4 can be obtained by reacting a compound of formula Ic.3 with hydrazine in acetic acid and optionally in a solvent at temperatures between 20 and 120 degrees Celsius. The synthesis route to the phthalazinone derivative of the formula Ic is carried out analogously to the reactions as described for the synthesis of a compound of the general formula Ib.

The synthesis of phthalazinone derivatives of the formula Ic, in particular of the starting compounds and the subsequent derivatization, is illustrated by a synthesis scheme 8 of a specific compound in which the abbreviations LAH lithium aluminum hydride, BuLi n-butyllithium, DMF dimethylformamide, MeOH methanol and Ms-Cl methanesulfonyl chloride mean.

Reaction scheme 8

Gemäß des vierten Falls, in dem Q -N=N- (llld) bedeutet, wird ein o-Amino- benzamid-Derivat der Formel ld.1 in Gegenwart einer geeigneten Nitrit- Verbindung und einer Säure über eine Diazoniumzwischenstufe zu einem Benzotriazinon-Derivat der Formel Id umgesetzt. Die Umsetzung ist in nachfolgendem Reaktionsschema 9, in dem der Übersichtlichkeit halber die Substituenten L¹, L², L³ am Phenylring weggelassen wurden, veranschaulicht.

According to the fourth case, in which Q is -N = N- (IIId), an o-aminobenzamide derivative of the formula Id.1 in the presence of a suitable nitrite compound and an acid via a diazonium intermediate becomes a benzotriazinone derivative the formula Id implemented. The reaction is illustrated in the following Reaction Scheme 9, in which, for the sake of clarity, the substituents L ¹ , L ² , L ³ on the phenyl ring have been omitted.

Reaction scheme 9:

NaN0 ₂ / HCI

Preferably, a compound of general formula Id.1 is reacted in a solvent such as methanol in the presence of a mineral acid, for example hydrochloric acid, and a salt containing the nitrite ion at a temperature between -10 ° C and 30 ° C. Advantageously, the reaction of the amino compound ld.1 proceeds with sodium nitrite in a molar ratio of 1 + 0.25: 1.5 + 0.25 in methanol as a solvent and in the presence of hydrochloric acid. According to the fifth case, in which Q signifies -CO-NR ⁹ - (llle), an o-aminobenzamide derivative of the formula le.1 is converted in the presence of CDI to a quinazolinedione derivative of the formula Ie. CDI is used for the benzamide derivative of the formula le.1 in a molar ratio of greater than or equal to 1 and the reaction is carried out at least partially in a temperature range from 35 ° C to 100 ° C, preferably in the range of the boiling temperature of the reaction mixture. The reaction is illustrated in the following Reaction Scheme 10, in which, for reasons of clarity, the substituents L ¹ , L ² , L ³ on the phenyl ring have been omitted.

Reaction Scheme 10:

CDI

According to the sixth case, in which Q denotes -CR ⁸ = N- (Ulf), an o-aminobenzamide derivative of the formula If 1 with a carboxylic acid R ⁸ COOH and / or a corresponding activated carboxylic acid derivative is added to the quinazolinone derivative. Derivative of the formula If implemented. Suitable activated carboxylic acid derivatives are, for example, esters, ortho-esters, carboxylic acid chlorides and anhydrides. The optionally activated carboxylic acid becomes the carboxylic acid amide compound of Formula lf.1 used in a molar ratio greater than or equal to 1 and the reaction is carried out at least partially in a temperature range of 35 ° C to 100 ° C, preferably in the range of the boiling temperature of the reaction mixture. The reaction is illustrated in the following Reaction Scheme 11, in which, for reasons of clarity, the substituents L ¹ , L ² , L ³ on the phenyl ring have been omitted.

Reaction scheme 11:

R ° COOH

The synthesis of quinazolinone derivatives of the formula If, in particular of the starting compounds, is illustrated by a synthetic scheme 12 of a specific compound in which the abbreviations CDI for carbonyldiimidazole, TBTU for 2- (1H-benzotriazol-1-yl) -1,1, 3,3-tetramethyluronium tetrafluoroborate and NEt ₃ can be used for triethylamine. First, the synthetic schemes of the two starting compounds 1 and 2 are shown. Reaction scheme 12

81/334

The starting compounds 1_ and 2 are linked via an amide linkage using TBTU. The nitro group ortho to the amide bond obtained is reduced to the amine in the presence of PtO ₂ . The ring closure to quinazolinone is carried out using a carboxylic acid, here formic acid.

According to the seventh case, in which Q represents -CO- (IIIg), an isobenzofurandione derivative of the formula Ig.2 is reacted with an amine compound of the formula Ig.1 to give the isoindoldione derivative of the formula Ig. The reaction is illustrated in the following Reaction Scheme 13, in which, for reasons of clarity, the substituents L ¹ , L ² , L ³ on the phenyl ring have been omitted. Reaction Scheme 13:

The isobenzofurandione derivative lg.2 is reacted in a solvent such as acetic acid with an amine of the general formula Ig.1 in a molar ratio of 1 + 0.25: 1, 5 + 0.25. The temperature in the reaction is preferably at the boiling point of the solvent.

However, the isoindoldione derivative of the formula Ig can also be obtained according to the following Synthetic Scheme 14. The illustrated synthesis of a single compound can be readily modified by the skilled person to other compounds of formula Ig optionally modified. First, the isoindoldione function is obtained from an isobenzofurandione derivative with attachment of an amine, and then a further aryl group is added by means of Suzuki coupling in the presence of Pd [0]. Reaction scheme 14

The previously described synthesis possibilities of the compounds according to the invention can be readily modified and / or supplemented with the skilled person, at least in principle by known processes, as described for example in Houben-Weyl methods of organic chemistry with regard to the individual compounds to be synthesized.

In the reactions described above, optionally present reactive groups such as hydroxyl, carboxy, amino or imino groups can be protected by literature methods during the reaction by conventional protecting groups which are cleaved again after the reaction, in particular the usual protective groups in peptide chemistry can be used become. Information on this can be found, for example, in WO 98/11128.

In principle, stereoisomeric compounds of the formula (I) can be separated by customary methods. The separation of the respective diastereomers succeeds due to their different physicochemical properties, eg by fractionated Crystallization from suitable solvents, by high pressure liquid or column chromatography using chiral or preferably achiral stationary phases.

As mentioned above, the compounds of the formula (I) can be converted into their salts, in particular for the pharmaceutical application, into their physiologically and pharmacologically tolerable salts. These salts may be present on the one hand as physiologically and pharmacologically acceptable acid addition salts of the compounds of the formula (I) with inorganic or organic acids. On the other hand, in the case of acidically bound hydrogen by reaction with inorganic bases, the compound of formula (I) can also be converted into physiologically and pharmacologically acceptable salts with alkali metal or alkaline earth metal cations as the counterion. Hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulphonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid are suitable for the preparation of the acid addition salts. Furthermore, mixtures of the abovementioned acids can be used. For the preparation of the alkali metal and alkaline earth metal salts of the compound of formula (I) with acidic hydrogen are preferably the alkali and alkaline earth metal hydroxides and hydrides into consideration, the hydroxides and hydrides of the alkali metals, especially of sodium and potassium preferably, sodium and potassium hydroxide are particularly preferred.

The compounds of the present invention, including the physiologically acceptable salts, have activity as antagonists of the MCH receptor, particularly the MCH-1 receptor, and show good affinities in MCH receptor binding studies. Pharmacological test systems for MCH antagonistic properties are described in the following experimental section.

As antagonists of the MCH receptor, the compounds of the invention are advantageously useful as pharmaceutical agents for the prophylaxis and / or treatment of phenomena and / or diseases caused by MCH or in another causal relationship with MCH. In general, the compounds according to the invention have low toxicity, good oral absorbability and intracerebral transitivity, in particular cerebral activity.

Therefore, MCH antagonists which have at least one compound of the invention, especially in mammals, such as rats, mice, guinea pigs, rabbits, dogs, cats, sheep, horses, pigs, cattle, monkeys and humans, for the treatment and / or prophylaxis of Phenomena and / or diseases caused by MCH or in another causal relationship with MCH.

Diseases caused by MCH or otherwise causally related to MCH include, in particular, metabolic disorders, such as obesity, and eating disorders, such as bulimia, including bulimia nervosa. Obesity includes primarily obesity, hyperinsulinic obesity, hyperplasmic obesity, hyperphyseal obesity, hypoplasmic obesity, hypothyroid obesity, hypothalamic obesity, symptomatic obesity, infantile obesity, upper body obesity, alimentary obesity, hypogonadal obesity, central obesity. Furthermore, cachexia, anorexia and hyperphagia are to be mentioned in this indication environment. In particular, compounds of the present invention may be useful in reducing hunger, curbing appetite, controlling eating behavior and / or inducing satiety,

In addition, diseases caused by MCH or otherwise causally related to MCH may include hyperiipidemia, cellulitis, fat accumulation, malignant mastocytosis, systemic mastocytosis, emotional disorders, affective disorders, depression, anxiety, reproductive disorders, memory disorders, forms of Dementia and hormonal disorders are counted.

Compounds of the invention are also useful as agents for the prophylaxis and / or treatment of other diseases and / or disorders, in particular those associated with obesity, such as diabetes, diabetes mellitus, especially type II diabetes, hyperglycemia, especially chronic hyperglycemia, diabetic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, etc., insulin resistance, pathological glucose tolerance, cardiovascular disease, especially arteriosclerosis and hypertension, and gonitis suitable.

MCH antagonists and formulations according to the invention can advantageously be used in combination with an alimentary therapy, such as, for example, an alimentary diabetes therapy, and exercise.

Another indication for which the compounds of the invention are advantageously useful is the prophylaxis and / or treatment of voiding disorders such as urinary incontinence, overactive bladder, urinary urgency, nocturia, enuresis, with overactive bladder and urinary urgency with or without benign prostatic hyperplasia Need to be connected.

The dosage required to achieve a corresponding effect is expediently from 0.001 to 30 mg / kg body weight, preferably from 0.01 to 5 mg / kg body weight, by intravenous or subcutaneous administration, and from 0.01 to 50 mg / kg by oral, nasal or inhalative administration Body weight, preferably 0.1 to 30 mg / kg body weight, in each case 1 to 3 times daily.

For this purpose, the compounds of general formula I according to the invention, optionally in combination with others can be

Active substances, as described in more detail below, together with one or more physiologically acceptable adjuvants, inert conventional carriers and / or diluents, e.g. with corn starch, lactose, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerine,

Water / sorbitol, water / polyethylene glycol, propylene glycol, cetyl stearyl alcohol, carboxymethyl cellulose or fatty substances such as hard fat or their suitable mixtures, in conventional pharmaceutical preparations such as tablets, Dragees, capsules, wafers, powders, granules, solutions, emulsions, syrups, inhalation aerosols, ointments, suppositories.

In addition to medicaments, the invention also encompasses compositions comprising at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention in addition to optionally one or more physiologically acceptable excipients. Such compositions may, for example, also be foodstuffs which may be solid or liquid, in which the compound according to the invention is incorporated.

For the above-mentioned combinations, suitable further active substances are, in particular, those which, for example, enhance the therapeutic efficacy of an MCH antagonist according to the invention with regard to one of the indicated indications and / or which allow a reduction in the dosage of an MCH antagonist according to the invention. Preferably, one or more further active substances are selected from the group consisting of

- drugs for the treatment of diabetes,

- agents for the treatment of diabetic complications, - agents for the treatment of obesity, preferably non-MCH antagonists,

- agents for the treatment of high blood pressure,

- active substances for the treatment of hyperlipidemia, including arteriosclerosis,

- agents for the treatment of arthritis, - agents for the treatment of anxiety,

- agents for the treatment of depression.

The aforementioned classes of active compounds are explained in more detail below by means of examples.

Examples of drugs for the treatment of diabetes are insulin sensitizers, insulin secretagogues, biguanides, insulins, α-glucosidase inhibitors, β3 adreno receptor agonists. Insulin sensitizers include pioglitazones and its salts (preferably hydrochlorides), troglitazones, rosiglitazones and its salts (preferably maleates), JTT-501, G 1-262570, MCC-555, YM-440, DRF-2593, BM-13-1258, KRP-297, R-119702, GW-1929.

Insulin secretion enhancers include sulfonylureas such as tolbutamide, chlorpropamide, trazamide, acetohexamide, glydlopyramide and its ammonium salts, glibenclamide, gliclazide, glimepiride. Further examples of insulin secretion accelerators are repaglinide, nateglinide, mitiglinide (KAD-1229), JTT-608.

Biguanides include metformin, buformin, phenformin.

Insulins include insulins derived from animals, particularly cattle or swine, semi-synthetic human insulins enzymatically synthesized from animal-derived insulin, human insulin obtained by genetic engineering, for example, from Escherichia coli or yeasts. Further, insulin is understood as meaning insulin zinc (containing 0.45 to 0.9% by weight of zinc) and protamine insulin zinc available from zinc chloride, protamine sulfate and insulin. In addition, insulin may come from

Insulin fragments or derivatives (for example, INS-1, etc.) can be obtained.

Insulin may also include different types, for example with regard to the time of onset and duration of action ("ultra-immediate action type",

"immediate action type", "two-phase type", "intermediate type", "prolonged action type", etc.), which are selected depending on the pathological condition of the patients.

Glucosidase inhibitors include acarbose, voglibose, miglitol,

Emiglitates.

β3 adreno receptor agonists include AJ-9677, BMS-196085, SB-226552, AZ40140. Other than the aforementioned drugs for the treatment of diabetes include ergoset, pramlintide, leptin, BAY-27-9955 and glycogen phosphorylase inhibitors, sorbitol dehydrogenase inhibitors, protein tyrosine phosphatase 1 B inhibitors, dipeptidyl protease inhibitors, glipazides, glyburides.

Agents for the treatment of diabetic complications include, for example, aldose reductase inhibitors, glycation inhibitors, protein kinase C inhibitors.

Aldose reductase inhibitors are, for example, Tolrestat, Epalrestat, Imirestat, Zenarestat, SNK-860, Zopolrestat, ARI-50Ϊ, AS-3201.

An example of a glycation inhibitor is pimagedine.

Protein kinase C inhibitors are, for example, NGF, LY-333531.

Alprostadil, thiapride hydrochloride, cilostazol, mexiletine hydrochloride, ethyl eicosapentate, memantine, pimagedine (ALT-) are other than the aforementioned active ingredients for the treatment of diabetic complications.

711).

Agents for the treatment of obesity, preferably other than MCH antagonists, include lipase inhibitors and anorectics.

A preferred example of a lipase inhibitor is orlistat.

Examples of preferred anorectic agents are phentermine, mazindol, dexfenfluramine, fluoxetine, sibutramine, baiamine, (S) -sibutramine, SR-141716, NGD-95-1.

Other than the aforementioned agents for the treatment of obesity include lipstatin. Furthermore, for the purposes of this application to the drug group of anti-obesity drugs and anorectics are counted, with the ß ₃ agonists, thyromi metic agents and NPY antagonists are highlighted. The scope of the substances which may be considered as preferred antiobesity / anorectic agents is exemplified by the following list: phenylpropanolamine, ephedrine, pseudoephedrine, phentermine, a cholecystokinin A (hereinafter referred to as CCK-A) agonist, a monoamine reuptake Inhibitor (such as sibutramine), a sympathomimetic agent, a serotonergic agent (such as dexfenfluramine or fenfluramine), a dopamine antagonist (such as bromocriptine), a melanocyte-stimulating hormone receptor agonist or mimetic, an analog of the melanocyte-stimulating hormone, a cannabinoid receptor antagonist, an MCH antagonist, the OB protein (hereinafter referred to as leptin), a leptin analog, a leptin receptor

Agonist, a galanin antagonist, an Gl lipase inhibitor or reducer (such as orlistat). Other anorectics include bombesin agonists, dehydroepiandrosterone or its analogues, glucocorticoid receptor agonists and antagonists, orexin receptor antagonists, urocortin binding protein antagonists, agonists of the glucagon-like

Peptide-1 receptors such as exendin and ciliary neurotrophic factors such as axokines.

Agents for the treatment of hypertension include inhibitors of angiotensin converting enzyme, calcium antagonists, potassium channel openers, angiotensin II antagonists.

Inhibitors of the angiotensin converting enzyme include captopril, enalapril, alacepril, delapril (hydrochloride), lisinopril, imidapril, benazepril, cilazapril, temocapril, trandolapril, manidipine (hydrochloride).

Examples of calcium antagonists are nifedipine, amlodipine, efonidipine, nicardipine. Potassium channel openers include Levcromakalim, L-27152, AL0671, NIP-121.

Angiotensin II antagonists include telmisartan, losartan, candesartan cilexetil, valsartan, irbeartan, CS-866, E4177.

Agents for the treatment of hyperlipidemia, including arteriosclerosis, include HMG-CoA reductase inhibitors, fibrate compounds.

HMG-CoA reductase inhibitors include pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, lipantil, cerivastatin, itavastatin, ZD-

4522 and its salts.

Fibrate compounds include bezafibrates, clinofibrates, clofibrates, simfibrates.

Agents for the treatment of arthritis include ibuprofen.

Agents for the treatment of anxiety include chlordiazepoxides, diazepam, oxozolam, medazepam, cloxazolam, bromazepam, lorazepam, alprazolam, fludiazepam.

Agents for the treatment of depression include fluoxetine, fluvoxamine, imipramine, paroxetine, sertraline.

The dose for these active substances is expediently 1/5 of the usually recommended lowest dosage up to 1/1 of the normally recommended dosage.

In a further embodiment, the invention also relates to the use of at least one carboxylic acid amide compound according to the invention and / or a salt according to the invention for influencing the eating behavior of a mammal. This use is based in particular on the fact that compounds according to the invention may be suitable for reducing hunger, curbing appetite, controlling eating behavior and / or a To cause satiety. The eating behavior is favorably influenced so that the food intake is reduced. Therefore, the compounds of the invention find advantageous application for reducing body weight. Another use of the invention is to prevent an increase in body weight, for example, in people previously

Have taken measures to reduce weight and are then interested in maintaining the reduced body weight. In accordance with this embodiment, it is preferably a non-therapeutic use. Such a non-therapeutic use may be a cosmetic application, for example, for altering the appearance or an application for improving the general condition. The compounds of the invention are preferably used non-therapeutically for mammals, especially humans, who have no diagnosed eating disorders, no diagnosed obesity, bulimia, diabetes and / or no diagnosed voiding disorders, especially urinary incontinence. Preferably, the compounds of the invention are suitable for non-therapeutic use in humans whose body mass index (BMI), defined as the kilogram of body weight divided by height (in meters) squared, is below the value of 30, in particular below 25, lies.

The following examples are intended to explain the invention in more detail:

Preliminary remarks: Melting points, ¹ H-NMR and / or mass spectra are usually present for prepared compounds. Unless stated otherwise, R _f values were determined using DC precast plates Kieselgel 60 F254 (E. Merck, Darmstadt, Germany).

Article no. 1.05714) without chamber saturation. The Rf values determined under the name Alox were determined using TLC finished plates alumina 60 F254 (E. Merck, Darmstadt, Article No. 1.05713) without

Chamber saturation determined.

The indicated HPLC data were listed below

Parameters measured: Zorbax column (Agilent Technologies), SB (stable bond) - C18; 3.5 μm; 4.6 x 75 mm; Column temperature: 30 ° C; Flow: 0.8 mL / min; Injection volume: 5 μl; Detection at 254 nm.

Method A: Water: acetonitrile: formic acid 9: 1: 0.01 to 1: 9: 0.01 over 9 min Method B: water: acetonitrile: formic acid 9: 1: 0.01 to 1: 9: 0.01 over 4 min, then 6 min 1: 9: 0.01

If further information on the configuration is missing, it remains unclear whether they are pure enantiomers or whether partial or even complete racemization has occurred.

The following abbreviations are used above and below:

BOC anhydride tert-butyloxycarbonyl anhydride

CDI carbonyldiimidazole

CDT 1, 1'-carbonyldi (1, 2,4-triazole)

DMF dimethylformamide

Ethyl acetate / EtOAc ethyl acetate

Ether diethyl ether

HOBt 1-hydroxybenzotriazole hydrate

Hunig base N, N-diisopropyl-ethylamine conc. concentrated

Me methyl

MeOH methanol

RT room temperature (about 20 ° C)

TBTU 2- (1H-Benzotriazol-1-yl) -1,3,3-tetramethyluronium 'tetrafluoroborate

THF tetrahydrofuran eq. Equivalent calculates calculated. found

General working procedure I (TBTU coupling):

To a solution of the carboxylic acid (1.0 eq.) In THF or DMF are added successively triethylamine (1.5 eq.) And TBTU (1.0 eq.). The mixture Depending on the carboxylic acid is stirred for 10 min to 12 h between room temperature and 40 ° C before the amine (1.0 eq.) Is added. The reaction is stirred between room temperature and 40 ° C for 30 minutes to 2 hours before adding half saturated NaHCO ₃ solution. After extraction of the aqueous phase with a suitable solvent (eg ethyl acetate), the organic phase is dried over magnesium sulfate. The solvent is removed on a rotary evaporator; Further purification is carried out by column chromatography or HPLC. The reaction can also be carried out in the automatic synthesizer Chemspeed.

General Procedure II (CDT Coupling):

To a solution of the primary amine (1.0 eq.) In DMF (1 mmol / mL) is added at 0 ° C CDT (1 eq.) And stirred at 0 ° C for a further 30 min. The reaction is warmed to 25 ° C and triethylamine (3 eq.) Added. Then add the secondary amine (1.0 eq.) In DMF (0.25 mmol / mL) and heat the

Reaction solution for 30 min to 3 h at 60 to 80 ° C. DMF is removed in vacuo and the residue taken up with dichloromethane and 5% Na ₂ CO ₃ solution or with water and tert-butyl methyl ether. The organic phase is extracted with water and, if appropriate after drying over magnesium sulfate, the solvent is removed on a rotary evaporator; Further purification is carried out by column chromatography or crystallization. The reaction can also be carried out in the automatic synthesizer Chemspeed.

Example 1.1:

7- (4-chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-on

1.1.a. 4-bromo-2-nitro-benzoic acid

In a reaction mixture of 82 g (0.379 mol) of 4-bromo-2-nitro-toluene in 700 ml of pyridine and 500 ml of water are added in portions 174.5 g (1, 104 mol) of potassium permanganate within eight hours. The reaction mixture is stirred for 12 hours at 60.degree. Subsequently, another 20 g (0.092 mol) of 4-bromo-2-nitro-toluene, 50 ml of pyridine and 30 g (0.189 mol) of potassium permanganate are added successively. The reaction mixture is stirred for 12 hours at 60 ° C, treated with 200 ml of ethanol and heated to reflux for 30 minutes. Thereafter, the reaction mixture is filtered hot and the filtrate is concentrated on a rotary evaporator. The remaining residue is made alkaline with 10% sodium hydroxide solution and extracted with diethyl ether. The aqueous phase is separated and acidified with dilute hydrochloric acid. The resulting crystals are filtered off, washed with water, dried azeotropically with tetrahydrofuran and stirred with diisopropyl ether. Yield: 37 g (32.8% of theory) C7H ₄ BrN0 ₄ (M = 246.018) calc .: Mol peak (M + Na) +: 268/270 F: Mol peak (M + Na) +: 268/270

R value: 0.46 (silica gel, dichloromethane / methanol / acetic acid 8: 2: 0.1)

1.1.b. 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid To a solution of 1, 92 g (7.81 mmol) of 4-bromo-2-nitro-benzoic acid in 30 ml of dioxane are added successively 0.288 g (0.25 mmol ) Tetrakis (triphenylphosphine) -palladium, 1.25 g (7.99 mmol) of 4-chloro-phenylboronic acid in 30 ml of methanol and 2.31 g (21.7 mmol) of sodium carbonate in 14 ml of water. The reaction mixture is heated in a microwave for one hour at 300 watts to 110 ° C heated. Subsequently, the reaction mixture is concentrated on a rotary evaporator, the residue taken up in water and adjusted to pH 3 with 1 M hydrochloric acid. The aqueous solution is extracted with ethyl acetate. The organic phase is dried over sodium sulfate, the solvent is distilled off on a rotary evaporator and the residue is stirred with diisopropyl ether. Yield: 2.04 g (93.9% of theory) C ₁₃ H ₈ CINθ4 (M = 277.666) calc .: Mol peak (MH) ^" : 276 F: Mol peak (MH) ^" : 276

Rr value: 0.5 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.1.c. 4-cyanomethyl-benzoic acid ethyl ester

A solution of 500 g (2.057 mol) of ethyl 4-bromomethylbenzoate in 1000 ml of ethanol is added dropwise to a solution of 147.5 g (2.263 mol) of potassium cyanide in 250 ml of hot water. The reaction mixture is heated to reflux for one hour and stirred for 12 hours at room temperature. Another 73.7 g (0.5 mol) of potassium cyanide are added and heated to reflux for two hours. The solid present in the reaction mixture is filtered off and the filtrate is filtered through a mixture of silica gel and activated carbon. The resulting filtrate is concentrated and the residue poured into 1000 ml of water. The aqueous solution is extracted with tetrabutyl methyl ether and the organic phase extracted three times with water. The organic phase is then dried over magnesium sulfate and the solvent is distilled off on a rotary evaporator. Purification is carried out by column chromatography on silica gel (petroleum ether / ethyl acetate 8: 2). Yield: 164.46 g (42.2% of theory) C | i Hι ιN0 ₂ (M = 189,216) calc .: Mol peak (M + H) ⁺ : 190 F: Mol peak (M + H) ⁺ : 190

Rr value: 0.3 (silica gel, petroleum ether / ethyl acetate 8: 2)

1.1.d. 4-cyanomethyl-benzoic acid

A solution of 10 g (53 mmol) of 4-cyanomethyl-benzoic acid ethyl ester and 2.02 ml of a 1 M sodium hydroxide solution in 100 ml of ethanol is heated to reflux for one hour. Subsequently, the reaction solution is concentrated and the Residue with ice water added. It is as long as concentrated hydrochloric acid added dropwise to the reaction solution until no more precipitate. The precipitate is filtered off, washed twice with water and dried. Yield: 4.7 g (55% of theory) CgH ₇ N0 ₂ (M = 161, 162) Calculated: Mol peak (MH) ": 160 F: Mol peak (MH)": 160

1.1.e. (4-hydroxymethyl-phenyl) -acetonitrile

To a solution of 4.7 g (29 mmol) of 4-cyanomethyl-benzoic acid in 250 ml of tetrahydrofuran are added 5.17 g (32 mmol) of CDI and until the end of the

Gas evolution stirred. This reaction mixture is added dropwise to a solution of 3.29 g (87 mmol) of sodium borohydride in 200 ml of water in such a way that the

Temperature does not exceed 30 ° C. It will be stirred for two hours and the

Reaction mixture with potassium bisulfate solution adjusted to pH 3-4. It is then extracted with ethyl acetate, the organic phase over

Dried magnesium sulfate and the solvent was separated on a rotary evaporator.

Yield: 2.6 g (60.9% of theory)

CgHgNO (M = 147.178) calc .: Molpeak (M-H) -: 146 found: Molpeak (M-H) ": 146

1.1.f. (4-bromomethyl-phenyl) -acetonitrile

0.86 ml (9 mmol) of phosphorus tribromide are added dropwise at 0 ° C. to a solution of 2.6 g (17.66 mmol) (4-hydroxymethyl-phenyl) -acetonitrile in 25 ml of tert-butyl methyl ether. After completion of the reaction, the reaction mixture is added at room temperature with water, the organic phase separated and extracted in succession with sodium bicarbonate solution and water. The organic phase is dried over magnesium sulfate and the solvent is distilled off on a rotary evaporator. Yield: 2.9 g (78.1% of theory) C ₉ H ₈ BrN (M = 210.075) calc .: Mol peak (M + H) +: 209/211 Found: Mol peak (M + H) +: 209/211 1.1.g. (4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile

0.466 ml (5.44 mmol) of pyrrolidine and 1.366 g (9.82 mmol) of potassium carbonate are introduced into 20 ml of dimethylformamide. With stirring, 1.038 g (4.941 mmol) of (4-bromomethyl-phenyl) -acetonitrile are added and the reaction is carried out for 12 hours

Room temperature stirred. The reaction mixture is concentrated on a rotary evaporator and the residue extracted with Essigsäueethylester and water. The organic phase is dried over magnesium sulfate and the solvent is removed on a rotary evaporator. Yield: 0.732 g (74% of theory) C | ₃ Hι ₆ N ₂ (M = 200.286) calc .: Mol peak (M + H) +: 201 Found: Mol peak (M + H) +: 201

Rr value: 0.5 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.1.h 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine

A reaction mixture of 0.73 g (3.66 mmol) of (4-pyrrolidin-1-ylmethylphenyl) acetonitrile and 0.1 g of Raney nickel in 25 ml of methanolic ammonia solution

Hydrogenated at 50 ° C and 3 bar hydrogen for 9h.

Yield: 0.72 g (96.4% of theory) of C 13 H ₂ oN ₂ (M = 204.31) calc .: Mol peak (M + H) +: 205 F: Mol peak (M + H) +: 205

Rr value: 0.23 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.1.i. 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

A solution of 0.4 (1.44 mmol) 4'-chloro-3-nitro-biphenyl-4-carboxylic acid, 0.29 g (1.44 mmol) 2- (4-pyrrolidin-1-ylmethyl-phenyl) ethylamine, 0.46 g (1.44 mmol) of TBTU, 0.19 g (1.44 mmol) of HOBT and 0.42 ml (3 mmol) of triethylamine in 30 ml of tetrahydrofuran is stirred at room temperature for 14 hours. The reaction mixture is concentrated on a rotary evaporator, extracted with water and ethyl acetate and dried over magnesium sulfate. The purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol / ammonia = 90: 10: 1). Yield: 0.47 g (70.3% of theory) of C26H26CIN ₃ O ₃ (M = 463.96) calc .: Mol peak (M + H) +: 464/466 Found: Mol peak (M + H) + : 464/466

R _f value: 0.36 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.1.j. 4'-Chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

A reaction mixture of 0.47 g (1.01 mmol) of 4'-chloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide and 0, 1 g Raney nickel in 50 ml methanolic ammonia solution is hydrogenated for 24 hours at 20 ° C and 3 bar of hydrogen. The crude product is reacted further without purification. Yield: 0.46 g crude C-26 ^H 28CIN ₃ O (M = 433.98) calc .: Mol peak (M + H) +: 434/436 found: Mol peak (M + H) +: 434/436 R _f value: 0.34 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.1.k. 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

0.46 g (1, 06 mmol) of 4'-chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide and 5 ml of formic acid are 3h at

Room temperature and stirred for 2 h at 100 ° C. The reaction mixture is washed with

Added water, made alkaline with 6N sodium hydroxide solution and the precipitate sucked off. The precipitate is taken up in dichloromethane and over

Dried magnesium sulfate. The solvent is distilled off on a rotary evaporator and the residue triturated with diisopropyl ether.

Yield: 0.3 g (64.6% of theory)

Melting point: 178-179 ° C

C-27H26CIN3O (M = 443.98) calc .: Mol peak (M + H) +: 444 _F : Mol peak (M + H) +: 444 R _f value: 0.35 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) Example 1.2: 3- [2- (4-Pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7-p-tolyl-3H-quinazolin-4-one

1.2.a. 4'-methyl-3-nitro-biphenyl-4-carboxylic acid

Prepared analogously to Example 1.1. b from 4-bromo-2-nitro-benzoic acid and 4-methyl-phenyl-boronic acid.

Yield: 1.48 g (70.8% of theory)

C ₁₄ H-1 N0 ₄ (M = 257.24) calc .: Mol peak (MH) ^" : 256 F: Mol peak (MH) ^" : 256

Rr value: 0.54 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.2.b. 4'-Methyl-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

ber.: Molpeak (M+H)⁺: 444 gef.: Molpeak (M+H)+: 444Prepared analogously to Example 1.1. i from 4'-methyl-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.51 g (78.3% of theory)

Calc .: Molpeak (M + H) ⁺ : 444 Found: Mol peak (M + H) +: 444

Rr value: 0.35 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.2.c. 4'-Methyl-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.1. j of 4'-methyl-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.2 g (69.2% of theory) ^C 28 31 N ₃ O (M = 413.56) calc .: Mol peak (M + H) +: 414 F: Mol peak (M + H) + : 414 Rf value: 0.36 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) Example 1.3: 3- [2- (4-Pyrrolidin-1-ylmethylphenyl) ethyl] -7- (4-trifluoromethylphenyl) -3H-quinazolin-4-one

1.3.a. 4'-trifluoromethyl-3-nitro-biphenyl-4-carboxylic acid Prepared analogously to Example 1.1. b from 4-bromo-2-nitro-benzoic acid and 4-trifluoromethyl-phenyl-boronic acid. Yield: 1.24 g (49% of theory) C 1 ₄ H ₈ F ₃ N0 ₄ (M = 311, 21) calc .: Mol peak (MH) ^" : 310 F: Mol peak (MH) ^" : 310

R _f value: 0.3 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.3.b. 4'-Trifluoromethyl-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1.i from 4'-trifluoromethyl-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.36 g (49.3% of theory) C27H26 ^F 3N ₃ 0 ₃ (M = 497.52) calc .: Mol peak (M + H) +: 498 F: Mol peak (M + H) + : 498

Rr value: 0.3 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.3.c. 4'-Trifluoromethyl-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-y-methyl-1-phenyl) -ethyl] -amide

A reaction mixture of 0.1 g (0.2 mmol) of 4'-trifluoromethyl-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide and 0, 08 g of platinum oxide in 50 ml of ethyl acetate is hydrogenated at 20 ° C 2.5h. The catalyst is filtered off. The purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol / ammonia = 90: 10: 1). Yield: 0.06 g (63.8% of theory) C 27 H 28 N ₃ N ₃ O (M = 467.53) calc .: Mole peak (M + H) +: 468 F: Mol peak (M + H) +: 468 Rr value: 0.46 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.4: 7- (4-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

1.4.a. 4'-methoxy-3-nitro-biphenyl-4-carboxylic acid

Prepared analogously to Example 1.1. b from 4-bromo-2-nitro-benzoic acid and 4-methoxyphenylboronic acid. Yield: 0.38 g (48.9% of theory) C ₁₄ Hι - | N0 ₅ (M = 273.24) calc .: Mol peak (MH) ^" : 272 F: Mol peak (MH)": 272

Rr value: 0.39 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1 Ab 4'-Methoxy-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1. j from 4'-methoxy-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine.

ber.: Molpeak (M+H)+: 460 gef.: Molpeak (M+H)+: 460Yield: 0.23 g (57% of theory)

Calc .: Molpeak (M + H) +: 460 Found: Molepeak (M + H) +: 460

Rf value: 0.48 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) 1.4.c. 4'-Methoxy-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.3.c from 4'-methoxy-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.09 g (42% of theory) C 27 H ₃₁ N ₃ O ₂ (M = 429.56) calc .: Mol peak (M + H) +: 430 Found: Mol peak (M + H) +: 430

R _f value: 0.44 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.5:

7- (3,4-dichloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

1.5.a. 3 ', 4'-dichloro-3-nitro-biphenyl-4-carboxylic acid

Prepared analogously to Example 1.1.b from 4-bromo-2-nitro-benzoic acid and 3,4-dichloro-phenyl-boronic acid.

Yield: 0.72 g (28.4% of theory)

C ₁₃ H ₇ Cl N04 (M = 312.11) calc .: Mol peak (MH) ": 310/312/314 found: Mol peak (MH)": 310/312/314

Rr value: 0.39 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.5.b. 3 ', 4'-dichloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.1.i from 3', 4'- Dichloro-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.47 g C-26 (64.2% theory d.) 25Cl2N ₃ 0 ₃ (M = 498.41) calc .: molecular peak (M + H) +: 498/500/502 Found .: molecular peak ( M + H) +: 498/500/502 Rr value: 0.24 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.5.c. 3 ', 4'-dichloro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1, 3.c from 3', 4 'Dichloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.11 g (25% of theory) of C ₂ H 6 H 27 Cl ₂ N ₃ O (M = 468.43) calc .: Mol peak (M + H) +: 468/470/472 Found: Mol peak (M + H) +: 468/470/472 Rf value: 0.46 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.6:

7- (3-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3r7 ^, -quinazolin-4-one

1, 6.a. 3'-methoxy-3-nitro-biphenyl-4-carboxylic acid

Prepared analogously to Example 1.1, b from 4-bromo-2-nitro-benzoic acid and 3-methoxyphenylboronic acid. Yield: 0.39 g (73.6% of theory) of Cι ₄ H ₁ ιN0 ₅ (M = 273.24) calc .: Mole peak (M + H) +: 274 F: Mol peak (M + H ) +: 274

Rr value: 0.35 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1, 6.b. 3'-Methoxy-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1. i from 3'-methoxy-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.39 g (57% of theory) C27H ₂ 9N ₃ 0 ₄ (M = 459.55) calc .: Mol peak (M + H) +: 460 found: Mol peak (M + H) +: 460

Rr value: 0.23 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1, 6.c. 3'-Methoxy-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

ber.: Molpeak (M+H)+: 430 gef.: Molpeak (M+H)+: 430Prepared analogously to Example 1.1, j from 3'-methoxy-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.11 g (30.6% of theory)

Calc .: Molpeak (M + H) +: 430 Found: Molepeak (M + H) +: 430

Rr value: 0.36 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.7: 7- (4-Fluoro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one

1.7.a. 4'-fluoro-3-nitro-biphenyl-4-carboxylic acid

Prepared analogously to Example 1.1. b from 4-bromo-2-nitro-benzoic acid and 4-fluoro-phenyl-boronic acid.

Yield: 1.3 g (61.2% of theory) C ₁₃ H ₈ FN0 ₄ (M = 261, 21) calc .: Mol peak (MH) ": 260 F: Mol peak (MH) ^" : 260

Rr value: 0.34 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.7.b. 4'-fluoro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1.i of 4'-fluoro-3-nitro-biphenyl-4-carboxylic acid and

2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.38 g (57.8% of theory) of C 6 H 26 N ₃ O ₃ (M = 447.51) calc.: Mole peak (M + H) +: 448. : Molepeak (M + H) +: 448

Rr value: 0.24 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.7.c. 4'-fluoro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.3.c from 4'-fluoro-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.06 g (32% of theory) of C ₂ H 6H28FN ₃ O (M = 417.53) calc .: Mol peak (M + H) +: 418 F: Mol peak (M + H) +: 418

Rf value: 0.63 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.8:

7- (4-Ethyl-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-on

ber.: Molpeak (M-H)": 268 gef.: Molpeak (M-H)-: 268 Rf-Wert: 0.39 (Kieselgel, Dichlormethan/Methanol/Essigsäure 9:1 :0.1 )1.8.a. 4'-Vinyl-3-nitro-biphenyl-4-carboxylic acid Prepared analogously to Example 1.1.b from 4-bromo-2-nitro-benzoic acid in and 4-vinyl-phenyl-boronic acid. Yield: 0.58 g (53% of theory)

Calc .: Molpeak (MH) ": 268 Found: Molepeak (MH) -: 268 Rf value: 0.39 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.8.b. 4'-Vinyl-3-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.1. i from 4'-vinyl-3-nitro-biphenyl-4-carboxylic acid and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.38 g (56.8% of theory) C ₂₈ H ₂ gN ₃ 0 ₃ (M = 455.56) calc .: Mol peak (M + H) +: 456 F: Mol peak (M + H ) +: 456

Rr value: 0.21 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.8.c. 4'-Ethyl-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.3.c from 4'-vinyl-3-nitro- biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide. Yield: 0.15 g (63.9% of theory) of C2 ₈ H ₃₃ N ₃ O (M = 427.59) calc .: Mol peak (M + H) +: 428 F: Mol peak (M + H) +: 428 Rf value: 0.47 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

The following compounds were prepared analogously to Example 1.1.k.

Rr value: A = (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Example 1.9

1.9.a 7- (4-Trifluoromethylphenyl) -2-methyl-3- [2- (4-pyrrolidin-1-ylmethylphenyl) ethyl] -3H-quinazolin-4-one

A solution of 0.07 g (0.15 mmol) of 4'-trifluoromethyl-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (see example 1.3.c) in 4 ml of acetic acid and 0.028 ml (0.3 mmol) of acetic anhydride is refluxed for 12 hours. The reaction solution is diluted with water, adjusted to pH 8 with dilute sodium hydroxide solution and extracted with dichloromethane. The organic phase is dried over magnesium sulfate. Purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol / ammonia 90: 10: 1). Yield: 0.008 g (11% of theory) C ₂ g H _{2 8} F ₃ N ₃ O (M = 491, 56) Calc .: Mol peak (M + H) +: 492 Found: Mol peak (M + H) +: 492

Rr value: 0.36 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

Analogous to Example 1.9. a, the following compounds were prepared:

R _f value: A = (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) Example 1.10: 2-Methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7- p-Tolyl-3H-quinazolin-4-one Example 1.11: 7- (4-Chloro-phenyl) -2-methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H- quinazolin-on-4

Example 1.12

1.12.a 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -1H-quinazoline-2,4-dione A reaction mixture of 0.3 g (0.69 mmol) of 4'-chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (see example 1.1, j) and 0.1 g (0.65 mmol) of CDI in 50 ml of tetrahydrofuran is heated to reflux for 24 hours. Subsequently, a further 0.1 g of CDI are added and the reaction mixture is heated to reflux for a further 24 hours. The

Reaction mixture is concentrated on a rotary evaporator. Purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol / ammonia 60: 1: 0.1). Yield: 0.2 g (62.9% of theory) Melting point: 274-276 ° C. C27H26CIN3O2 (M = 459 , 98) Calcd .: Mol peak (M + H) +: 460/462 Found: Mol peak (M + H) +: 460/462

R _f value: 0.1 (silica gel, dichloromethane / methanol / ammonia 50: 1: 0.1)

Example 1.13:

7- (4-Chloro-phenyl) -3- {2- [4 - ((S) -2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

1, 13.a [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -acetonitrile Prepared analogously to Example 1.1. g of 2- (S) -methoxymethyl-pyrrolidine and (4-bromomethyl-phenyl) -acetonitrile. Yield: 0.9 g (51.6% of theory) C ₁ H ₅ H ₂ O ₂ (M = 244.33) calc .: Mole peak (M + H) +: 245 F: Mol peak (M + H) ⁺ : 245

Rr value: 0.3 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.13, b 2- [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethylamine Prepared analogously to Example 1.1. h from [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -acetonitrile. Yield: 0.5 g (54.7% of theory) C ₅ H ₄ N ₂ O (M = 248.37) calc .: Mol peak (M + H) +: 249 found: Mol peak (M + H) +: 249

Rr value: 0.3 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

1.13.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide Prepared analogously to Example 1.1.i of 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethylamine. Yield: 0.5 g (54.7% of theory) C ₂ 8H ₃ oCIN ₃ 0 ₄ (M = 508.02) calc .: Mol peak (M + H) +: 508/510 Found: Molpeak (M. + H) +: 508/510 R _f value: 0.6 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

1.13.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (2- (S) -methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} - amide. Yield: 0.24 g (51% of theory) C2 ₈ H ₃ 2CIN ₃ 0 ₂ (M = 478.03) calc .: Mole peak (M + H) +: 478/480 F: Mol peak (M + H ) +: 478/480

Rr value: 0.2 (silica gel, dichloromethane / methanol / ammonia 10: 1: 0.1)

Example 1.14:

7- (4-chloro-phenyl) -3- [2- (4-dimethylaminomethyl-phenyl) -ethyl] -3H-quinazolin-4-one

1.14.a (4-Dimethylaminomethyl-phenyl)-acetonitril

1.14.a (4-dimethylaminomethyl-phenyl) -acetonitrile

Prepared analogously to Example 1.1. g of dimethylamine and (4-bromomethyl-phenyl) - acetonitrile.

Yield: 1.0 g (30% of theory) Cι - | H ₁₄ N ₂ (M = 174.24) calc .: Mol peak (M + H) +: 175 found: Mol peak (M + H) +: 175

Rr value: 0.2 (silica gel, cyclohexane / ethyl acetate 1: 1)

ber.: Molpeak (M+H)+: 179 gef.: Molpeak (M+H)+: 1791.14.b 2- (4-Dimethylaminomethyl-phenyl) -ethylamine Prepared analogously to Example 1.1.h from (4-dimethylaminomethyl-phenyl) -acetonitrile. Yield: 1.0 g crude

Calc .: Molpeak (M + H) +: 179 Found: Molepeak (M + H) +: 179

Rr value: 0.2 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

1.14.c 4 '- Chloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-dimethylaminomethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1.i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- (4-dimethylaminomethyl-phenyl) -ethylamine. Yield: 0.5 g (63.4% of theory) C2 H ₂₄ CIN ₃ 0 ₃ (M = 437.93) calc .: Mol peak (M + H) +: 438/440 Found: Mol peak (M + H) +: 438/440

Rr value: 0.35 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

1.14.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-dimethylaminomethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid [2-

(4-dimethylaminomethyl-phenyl) -ethyl] -amide

Yield: 0.2 g (43% of theory) C 24 H 26 CIN ₃ O (M = 407.94) calc .: Mol peak (M + H) +: 408/410 Found: Mol peak (M + H) +: 408 / 410

R _f value: 0.2 (silica gel, dichloromethane / methanol / ammonia 20: 1: 0.1) Example 1.15:

7- (4-chloro-phenyl) -3- [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-on

1.15.a (4-piperidin-1-ylmethyl-phenyl) -acetonitrile

Prepared analogously to Example 1.1.g from piperidine and (4-bromomethyl-phenyl) - acetonitrile.

Yield: 1.6 g (39% of theory)

C- | ₄ H _{1 8} N ₂ (M = 214.31) calc .: Mol peak (M + H) +: 215 F: Mol peak (M + H) +: 215

R _f value: 0.4 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.15.b 2- (4-piperidin-1-ylmethyl-phenyl) -ethylamine

Prepared analogously to Example 1.1.h from (4-piperidin-1-ylmethylphenyl) acetonitrile. Yield: 1.4 g (85.9% of theory) of C ₄ H ₂ 2N ₂ (M = 218.34). : Molepeak (M + H) +: 219 Found: Molepeak (M + H) +: 219

R _f value: 0.2 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

1.15.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.1.i of 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- (4-piperidin-1-ylmethyl-phenyl) -ethylamine.

Yield: 0.07 g (40.7% of theory) C ₂ 7H28CIN ₃ 0 ₃ (M = 477.99) calc .: Mol peak (M + H) +: 478/480 F: Mol peak (M + H ) +: 478/480

Rr value: 0.5 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1) 1.15.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid [2-

(4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide

Yield: 0.05 g (76.4% of theory)

C ₂ 7H ₃₀ CIN ₃ O (M = 448.01)

Example 1.16:

7- (4-chloro-phenyl) -3- [2- (4-morpholin-4-yimethyl-phenyl) -ethyl] -3H-quinazolin-4-on

1.16.a (4-morpholin-4-ylmethyl-phenyl) -acetonitrile

Prepared analogously to Example 1.1. g of morpholine and (4-bromomethylphenyl) acetonitrile. Yield: 1, 63 g (98.9% of theory.) C ₃ Hι ₆ N ₂ 0 (M = 216.28) calc .: molecular peak (M + H) +: 217 Found .: molecular peak (M + H) +: 217

R _f value: 0.33 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.16.b 2- (4-morpholin-1-ylmethyl-phenyl) -ethylamine

Prepared analogously to Example 1.1.h from (4-morpholin-1-ylmethyl-phenyl) -acetonitrile. Yield: 1.65 g (99.4% of theory) of C ₁ H2 ₃ H ₂ O ₂ 0 (M = 220.31) Mole peak (M + H) +: 221 Found: Mole peak (M + H) +: 221 R _f value: 0.54 (silica gel, dichloromethane / ethanol / ammonia 9: 1: 0.1)

1.16.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid [2- (4-morpholin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- (4-morpholin-1-ylmethyl-phenyl) -ethylamine. Yield: 0.53 g (76.6% of theory) of C 6 H 26 CIN ₃ O (M = 479.97) calc .: Mole peak (M + H) +: 480/482 F: mole peak (M + H) + : 480/482

Rr value: 0.5 (silica gel, dichloromethane / ethanol / ammonia 90: 1: 0.1)

1.16.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-morpholin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 1.3.c from 4'-chloro-3 -nitro-biphenyl-4-carboxylic acid [2- (4-morpholin-1-ylmethyl-phenyl) -ethyl] -amide Yield: 0.45 g (90.6% of theory) C26 28 ^CIN 3θ ₂ (M. = 449.98) calc .: Mol peak (M + H) +: 450/452 Found: Mol peak (M + H) +: 450/452 R _f value: 0.67 (silica gel, dichloromethane / ethanol / ammonia 90: 1 : 0.1)

Analogously to Example 1.1. k, the following compounds were prepared:

Rr value: A = (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) C = (silica gel, dichloromethane / methanol / ammonia 10: 1: 0.1) D = (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1)

Example 1.17 7- (4-Chloro-phenyl) -3- {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -3H-quinazolin-4-one

1.17.a (6-Chlor-pyridin-3-yl)-acetonitril

1.17.a (6-chloro-pyridin-3-yl) -acetonitrile

To a solution of 6.91 g (41.66 mmol) of potassium iodide and 2.24 g (49.01 mmol) of sodium cyanide in 400 mL of an ethanol water (9: 1) mixture is added a solution of 7.5 g (41 , 66 mmol) 2-chloro-5-chloromethyl-pyridine, dissolved in 100 ml of ethanol, was added dropwise. Subsequently, the reaction mixture is heated to 85 ° C for five hours. The solvent is largely distilled off in vacuo and the residue extracted with water and ethyl acetate. The organic phase is washed three times with water and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: dichloromethane / ethanol). Yield: 2.9 g (45.6% of theory) C ₇ H ₅ CIN ₂ (M = 152.58) calc .: Mol peak (M + H) +: 151/153 Found: Mol peak (M + H ) +: 151/153.

1.17.b [6- (4-Methyl-piperazin-1-yl) -pyridin-3-yl] -acetonitrile A solution of 2.9 g (19 mmol) of (6-chloro-pyridin-3-yl) -acetonitrile , 5.27 ml (38 mmol) of triethylamine and 2.1 ml (19 mmol) of N-methylpiperazine in 50 ml of n-butanol is heated for two hours in the microwave at 180 ° C. The solvent is distilled off in vacuo, the residue is suspended in water and then extracted with ethyl acetate. The combined organic phases are extracted three times with water and dried over sodium sulfate. The purification is carried out by column chromatography on Alox (eluent: petroleum ether / ethyl acetate 1: 1). Yield: 1 g (24.6% of theory). Melting point: 58-59 ° CC ₁₂ H-ι ₆ N ₄ (M = 216.28) calc .: molecular peak (M + H) +: 217 Found .: molecular peak (M + H) +: 217

Rr value: 0.35 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1).

1.17.c 2- [6- (4-Methyl-piperazin-1-yl) -pyridin-3-yl] -ethylamine Prepared analogously to Example 1.1. i from [6- (4-methylpiperazin-1-yl) pyridin-3-yl] acetonitrile.

Yield: 0.94 g (96% of theory) of C ₂ H ₂ NO ₄ (M = 220.32) calc .: Mole peak (M + H) +: 221 F: Mol peak (M + H) +: 221 ,

1.17.d 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [6- (4-methyl-piperazin-1-yl) -pyridin-3-yl] -ethyl} -amide

Prepared analogously to Example 1.1.j from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- [6- (4-methyl-piperazin-1-yl) -pyridin-3-yl] ethylamine.

Yield: 0.48 g (36.7% of theory) Melting point: 158-159 ° C

C25H26 ^CIN 5θ ₃ (M = 479.97) calc .: Mol peak (M + H) +: 480/482 found: Mol peak (M + H) +: 480/482.

1.17.e 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -amide

Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2- [6-

(4-methyl-piperazin-1-yl) -pyridin-3-yl] -ethyl} -amide.

Yield: 0.12 g (64% of theory) Melting point: 198-199 ° CC 5H28CIN ₅ O (M = 449.98) calc .: Mol peak (M + H) +: 450/452 Found: Mol peak (M + H) +: 450/452.

1.17.f 7- (4-Chloro-phenyl) -3- {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -3H-quinazolin-4-one

Prepared analogously to Example 1.1.1 from 4'-chloro-3-amino-biphenyl-4-carboxylic acid {2-

[6- (4-Methyl-piperazin-1-yl) -pyridin-3-yl] -ethyl} -amide and formic acid.

Yield: 0.06 g (53.5% of theory)

Melting point: 263-264 ° C

C26 ^{H26 CIN} 5θ (M = 459.98) calc .: molecular peak (M + H) +: 460/462 Found .: molecular peak (M + H) +: 4460/462.

Example 1.18 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-benzo [d] [1,2,3] triazin-4-one

1.18.a 7- (4-Chloro-phenyl) -3- {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -3H-benzo [d] [1, 2, 3] triazin-4-one To a solution of 0.27 g (0.62 mmol) 4'-chloro-3-amino-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (see Example 1.1.j) in 10 ml of methanol and 1N hydrochloric acid at a temperature between 0 ° C and 5 ° C, a solution of 0.09 g (0.93 mmol) of sodium nitrite in 2 ml of water slowly dropped. Subsequently, the reaction mixture is stirred for three hours at room temperature, subsequently diluted with 30 ml of water and made alkaline with ammonia solution. The aqueous solution is extracted with ethyl acetate. The combined organic phases are washed three times with water, dried over sodium sulfate and over Activated carbon filtered. The solvent is removed and the residue is washed with diisopropyl ether. Yield: 0.09 g (32.5% of theory) Melting point: 151-152 ° C ^C 26 ^H 25 ^CIN 4 ° ( ^M = 444.96) calc .: Mol peak (M + H) +: 445/447 Found: Molpeak (M + H) +: 445/447

Rr value: 0.35 (silica gel, dichloromethane / ethanol = 10: 1).

Example 1.19 7- (4-Chloro-phenyl) -3- (4-pyrrolidin-1-ylmethylbenzyl) -3H-benzo [d] [1,2,3] triazin-4-one

1.19.a 4- (1-Pyrrolidin-1-yl-ethyl) -benzonitrile

Prepared analogously to Example 1.1.g from piperidine and 4-bromomethyl-benzonitrile Yield: 2.4 g (85.9% of theory) of C ₁₂ Hι ₄ N ₂ (M = 186.25) calc.: Molpeak (M + H ) +: 187 gef. : Molepeak (M + H) +: 187

Rr value: 0.63 (silica gel, dichloromethane / methanol / ammonia = 8: 2: 1).

1.19.b 4- (1-Pyrrolidin-1-yl-ethyl) -benzylamine

Prepared analogously to Example 1.1. h from 4- (1-pyrrolidin-1-yl-ethyl) -benzonitrile. Yield: 2.42 g (98.7% of theory) of CI ₈ N ₂ (M = 190.29) calc .: Molpeak (M. + H) +: 191 Found: Molepeak (M + H) +: 191 R _f value: 0.26 (silica gel, dichloromethane / methanol / ammonia = 90: 10: 1).

1.19.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid 4- (1-pyrrolidin-1-yl-ethyl) -benzylamide Prepared analogously to Example 1.1.i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- (4-4- (1-pyrrolidin-1-yl-ethyl) -benzylamine.) Yield: 0.28 g ( 28.8% of theory) ^c 25 ^H 24 ^CIN ₃ θ ₃ (M = 449.94)

Calcd .: Mol peak (M + H) +: 450/452 Found: Mol peak (M + H) +: 450/452.

1.19.d. 3-Amino-4'-chloro-biphenyl-4-carboxylic acid 4- (1-pyrrolidin-1-yl-ethyl) -benzylamide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid 4- (1-pyrrolidin-1-yl-ethyl) -benzylamide. Yield: 0.19 g (72.7% of theory) C25H26CIN3O (M = 419.95) calc .: Mol peak (M + H) +: 420/422 found: Mol peak (M + H) +: 420 / 422nd

1.19.e 7- (4-Chloro-phenyl) -3- [4- (1-pyrrolidin-1-yl-ethyl) -benzyl] -3H-benzo [d] [1,2,3] triazine-4 on

Prepared analogously to Example 1.18.a from 3-amino-4'-chloro-biphenyl-4-carboxylic acid-4-

(1-pyrrolidin-1-yl-ethyl) -benzylamide.

Yield: 0.045 g (31.4% of theory) Melting point: 147-148 ° C

C25H ₂₃ CIN 0 (M = 430.94) calc .: Mol peak (M + H) +: 431/433 Found: Mol peak (M + H) +: 431/433

Rr value: 0.3 (silica gel, dichloromethane / ethanol = 10: 1).

Example 1.20 5- (4-Fluoro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethylphenyl) ethyl] isoindole-1,3-dione

1.20.a 5-Bromo-2- {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -isoindole-1,3-dione A solution of 0.8 g (3.52 mmol) of 5-bromo-isobenzofuran-1,3-dione and 0.72 g (3.52 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (see Example 1.1.h) in 10 ml of acetic acid is heated to 110 ° C for four hours. The reaction mixture is then poured into water, made alkaline with 2N sodium hydroxide solution and the precipitate is filtered off. The precipitate is washed several times with water and dried. Yield: 0.5 g (34.3% of theory) C21 H ₂ 1 BrN 0 ₂ (M = 413.31) calc .: Mol peak (M + H) +: 413/415 Found: Mol peak (M + H) +: 413/415.

1.20.b. 5- (4-fluoro-phenyl) -2- {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -isoindol-

1, 3-dione

Prepared analogously to Example 1.1. b from 5-bromo-2- {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -isoindole-1, 3-dione and 4-fluoro-phenylboronic acid.

Yield: 0.01 g (4.8% of theory)

C27H25FN2O2 (M = 428.51) calc .: Mol peak (M + H) +: 429 found: Mol peak (M + H) +: 429.

Example 1.21: 7- (4-Chloro-phenyl) -3- {2- [4- (4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

ber.: Molpeak (M+H)+: 291 gef.: Molpeak (M+H)+: 291 R_f-Wert: 0.5 (Kieselgel, Cyclohexan/Essigsäureethylester 1 :1)1.21.a [4- (4-phenyl-piperidin-1-ylmethyl) -phenyl] -acetonitrile Prepared analogously to Example 1.1.g from 4-phenylpiperidine and (4-bromomethyl-phenyl) -acetonitrile. Yield: 3.8 g (98% of theory)

Calc .: Mol peak (M + H) +: 291 Found: Mol peak (M + H) +: 291 R _f value: 0.5 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.21.b 2- [4- (4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethylamine

Prepared analogously to Example 1.1. h from [4- (4-phenylpiperidin-1-ylmethyl) phenyl] acetonitrile.

ber.: Molpeak (M+H)+: 295 gef.: Molpeak (M+H)+: 295Yield: 3.6 g crude

Calc .: Molpeak (M + H) +: 295 Found: Molepeak (M + H) +: 295

Rr value: 0.49 (silica gel, dichloromethane / ethanol 20: 1)

1.21.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.1.i of 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- [4- (4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethylamine. Yield: 1.33 g (70.7% of theory) of C33H ₃₂ CIN ₃ 0 ₃ (M = 554.09) .: Molpeak (M + H) +: 554/556 Found: Molepeak (M + H) +: 554/556

Rr value: 0.58 (silica gel, dichloromethane / ethanol / ammonia 10: 1: 0.1)

1.21.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [4- (4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2-

[4- (4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Yield: 0.82 g (65.2% of theory) C ₃₃ H ₃₄ CIN ₃ O (M = 524.11) calc .: Mol peak (M + H) +: 524/526/528 found: Molpeak (m.p. M + H) +: 524/526/528

Rr value: 0.65 (silica gel, dichloromethane / methanol 10: 1)

Example 1.22: 7- (4-Chloro-phenyl) -3- {2- [4- (4-phenylpiperazin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

1.22.a [4- (4-phenylpiperazin-1-ylmethyl) phenyl] acetonitrile

Prepared analogously to Example 1.1. g of 4-phenylpiperazine and (4-bromomethylphenyl) acetonitrile.

Yield: 3.7 g (97% of theory)

Cι H ₂ i N ₃ (M = 291, 39) calc .: Mol peak (M + H) +: 292 found: Mol peak (M + H) +: 292

R value: 0.6 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.22. b 2- [4- (4-phenylpiperazin-1-ylmethyl) -phenyl] -ethylamine Prepared analogously to Example 1.1. h from [4- (4-phenyl-1-piperazin-1-ylmethyl) phenyl] acetonitrile

ber.: Molpeak (M+H)+: 296 gef.: Molpeak (M+H)+: 296Yield: 1.1 g (28.6% of theory)

Calc .: Molpeak (M + H) +: 296 Found: Molepeak (M + H) +: 296

1.22.c 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (4-phenyl-1-piperazin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- [4- (4-phenyl-piperazin-1-ylmethyl) -phenyl] -ethylamine

Yield: 0.32 g (18.2% of theory) of C ₃₂ H ₃₁ CIN ₄ O ₃ (M = 555.08) Calculated: Mol peak (M + H) +: 555/557 Found: Molpeak (M. + H) +: 555/557

1.22. d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [4- (4-phenyl-1-piperazin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2-

[4- (4-phenyl-piperazin-1-ylmethyl) -phenyl] -ethyl} -amide Yield: 0.11 g (38.8% of theory) C ₃₂ H ₃₃ CIN ₄ O (M = 525.09) calc .: Mol peak (M + H) +: 525/527 Found: Mol peak (M + H) +: 525/527

Example 1.23:

7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

23.1. a [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -acetonitrile Prepared analogously to Example 1.1. g of 4-hydroxy-4-phenylpiperidine and (4-bromomethyl-phenyl) -acetonitrile. Yield: 3.8 g (98% of theory.) C ₂ oH22N ₂ 0 (= 306.41) calc .: molecular peak (M + H) +: 307. Found .: molecular peak (M + H) +: 307

Rr value: 0.1 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.23.b 2- [4- (4-Hydroxy-4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethylamine

Prepared analogously to Example 1.1. h from [4- (4-hydroxy-4-phenylpiperidin-1-ylmethyl) phenyl] acetonitrile

Yield: 3.36 g (92.1% of theory)

C ₂ oH26 ₂ 0 (M = 310.44) calc .: Mol peak (M + H) +: 311 Found: Mol peak (M + H) +: 311

Rr value: 0.1 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1)

1.23.C 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (4-hydroxy-4-phenyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethylamine Yield: 1.2 g (65.3% of theory) C ₃₃ H ₃ CIN ₃ O 4 (M = 570.09) calc .: Mol peak (M + H) +: 570/572 Found: Mol peak (M + H) +: 570/572

R _f value: 0.35 (silica gel, dichloromethane / methanol / ammonia 10: 1: 0.1)

1.23.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2-

[4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Yield: 1, 04 g (91, 5% of theory)

C ₃₃ H ₃₄ CIN ₃ 0 ₂ (M = 540.11)

Melting point: 175-180 ° C calc .: Mole peak (M + H) +: 540/542/544 Found: Molepeak (M + H) +: 540/542/544

Rr value: 0.34 (silica gel, dichloromethane / methanol / ammonia 10: 1: 0.1)

23.1. e. 7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

Prepared analogously to Example 1.1. k. of 4'-chloro-3-amino-biphenyl-4-carboxylic acid {2-

[4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide.

Yield: 0.025 g (8.2% of theory)

Melting point: 204-205 ° C

C ₃ H ₃ CIN ₃ 0 ₂ (M = 550.10) calc .: Mol peak (M + H) +: 550/552 Found: Mol peak (M + H) +: 550/552

Rr value: 0.46 (silica gel, dichloromethane / ethanol / ammonia 10: 1: 0.1)

Example 1.24:

7- (4-Chloro-phenyl) -3- {2- [4- (4-phenyl-3,6-dihydro-2H-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4 on

1.24.a.. 7-(4-Chlor-phenyl)-3-{2-[4-(4-phenyl-3,6-dihydro-2H-piperidin-1 - ylmethyl)-phenyl]-ethyl}-3H-chinazolin-4-on

1.24.a .. 7- (4-Chloro-phenyl) -3- {2- [4- (4-phenyl-3,6-dihydro-2H-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H -quinazoline-on-4

Prepared analogously to Example 1.1.k. of 4'-chloro-3-amino-biphenyl-4-carboxylic acid {2-

[4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide as a by-product in Example 123. e.

Yield: 0.08 g (27.1% of theory)

Melting point: 166-167 ° C

C ₃₄ H ₃₀ CIN ₃ O (M = 532.09) calc .: Mol peak (M + H) +: 532/534 Found: Mol peak (M + H) +: 532/534

Rr value: 0.57 (silica gel, dichloromethane / ethanol / ammonia 10: 1)

Example 1.25:

7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one

1.25.a [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -acetonitrile

Prepared analogously to Example 1.1. g from 3-aza-spiro [5.5] undecane and (4-bromomethyl-phenyl) -acetonitrile.

Yield: 3.38 g (98% of theory)

C- | gH ₂ 6N ₂ (M = 282.43) calc .: Mol peak (M + H) +: 283 found: Mol peak (M + H) +: 283

Rr value: 0.56 (silica gel, cyclohexane / ethyl acetate 1: 1)

1.25.b 2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethylamine

Prepared analogously to Example 1.1.h from [4- (3-aza-spiro [5.5] undec-3-ylmethyl) phenylj-acetonitrile

Yield: 3.33 g (96.6% of theory) C ₁₉ H ₃₀ N ₂ (M = 286.46) calc .: Mol peak (M + H) +: 287 found: Mol peak (M + H) +: 287

Rr value: 0.18 (silica gel, dichloromethane / ethanol 20: 1)

1.25.C 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and

2- [4- (3-Aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethylamine

Yield: 1 g (52.5% of theory)

C32H36CIN3O3 (M = 546.11): Molpeak (M + H) +: 546/548 Found: Molepeak (M + H) +: 546/548

Rr value: 0.3 (silica gel, dichloromethane / ethanol 20: 1)

1.25. d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid {2- [4- (3-aza-spiro [5.5] and n-dec-3-yl-methyl) -phenyl l ] -ethyl} -amide Yield: 0.8 g (84.7% of theory) C ₃₂ H ₃₈ CIN ₃ O (M = 516.13) calc .: Mol peak (M + H) +: 516/518 Found: Molpeak (M + H) +: 516/518

R _f value: 0.38 (silica gel, dichloromethane / methanol 10: 1)

Example 1.26:

7- (4-Chloro-phenyl) -3- (2- {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethyl) -3H-quinazolin-4-one

1.26.a {4- [4- (pyridin-2-yloxy) -piperidine-1-ylmethyl] -phenyl} -acetonitrile Prepared analogously to Example 1.1. g of 2- (piperidin-4-yloxy) -pyridine and (4-bromomethyl-phenyl) -acetonitrile. Yield: 0.91 g (49.8% of theory) of C ₉ H ₂ ι N ₃ O (M = 307.39) calc .: Mol peak (M + H) +: 308 F: Mol peak (M + H ) +: 308

Rr value: 0.49 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.26.b 2- {4- [4- (Pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethylamine Prepared analogously to Example 1.1. h from {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -acetonitrile

Yield: 0.92 g (99.8% of theory) C ₁₉ H 25 N ₃ O (M = 311, 43) calc .: Mole peak (M + H) +: 312 F: Mol peak (M + H) +: 312

Rr value: 0.16 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.26.C 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid (2- {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Prepared analogously to Example 1.1. i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethylamine. Yield: 0.8 g (97.2% of theory) C ₃₂ H ₃₁ CIN ₄ O ₄ (M = 571, 08) calc .: Mol peak (M + H) +: 571/573 Found: Mol peak (M + H) +: 571 / 573

Rr value: 0.52 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.26.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid (2- {4- [4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid (2-

{ ₄ - [ ₄ - (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Yield: 0.38 g (50% of theory) C ₃₂ H ₃₃ CIN ₄ O ₂ (M = 541, 09) Calcd .: Mol peak (M + H) +: 541/543 Found: Mol peak (M + H ) +: 541/543

Rr value: 0.5 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) Example 1.27:

7- (4-Chloro-phenyl) -3- (2- {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethyl) -3H-quinazolin-4-one

ber.: Molpeak (M+H)+: 307 gef.: Molpeak (M+H)+: 3071.27.a {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -acetonitrile Prepared analogously to Example 1.1.g from 2- (piperidin-4-ylamino) -pyridine and (4- Bromomethyl-phenyl) -acetonitrile. Yield: 1.57 g (86.1% of theory)

Calcd .: Mol peak (M + H) +: 307 Found: Mol peak (M + H) +: 307

Rr value: 0.43 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.27.b 2- {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethylamine Prepared analogously to Example 1.1.h from {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -acetonitrile Yield: 1.662 g (99.8% of theory) of CιgH ₂ 6N ₄ (M = 310.44) calc .: Mol peak (M + H) +: 311 Found: Molepeak (M + H) +: 311 R _f -value: 0.1 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

1.27.C 4'-Chloro-3-nitro-biphenyl-4-carboxylic acid (2- {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Prepared analogously to Example 1.1.i from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid and 2- {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethylamine. Yield : 0.36 g (43.8% of theory) C ₃ 2H ₃₂ CIN ₅ 0 ₃ (M = 570.09) calc .: Mol peak (M + H) +: 570/572 Found: Mol peak (M + H) +: 570/572

Rr value: 0.28 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) 1.27.d 4'-Chloro-3-amino-biphenyl-4-carboxylic acid (2- {4- [4- (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Prepared analogously to Example 1.3.c from 4'-chloro-3-nitro-biphenyl-4-carboxylic acid (2-

{ ₄ - [ ₄ - (pyridin-2-ylamino) -piperidin-1-ylmethyl] -phenyl} -ethyl) -amide

Yield: 0.29 g (85.7% of theory)

C ₃ H ₃₄ CIN ₅ O (M = 540.11) calc .: Mol peak (M + H) +: 540/542 Found: Mol peak (M + H) +: 540/542

Rr value: 0.27 (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1)

The following compounds were prepared analogously to Example 1.1.k.

Rr value: A = (silica gel, dichloromethane / methanol / ammonia 9: 1: 0.1) E = (silica gel, dichloromethane / ethanol 10: 1) F = (silica gel, dichloromethane / ethanol / ammonia 10: 1: 0.1)

Example 1.28 7- (4-Chloro-phenyl) -3- {2- [4- (4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [] [1, 2,3] triazin-4-one

1.28. a 7- (4-Chloro-phenyl) -3- {2- [4- (4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [1,2,3] triazine -4-one

Prepared analogously to Example 1.18.a from 4'-chloro-3-amino-biphenyl-4-carboxylic acid

{2- [4- (4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide.

Yield: 0.13 g (50.9% of theory)

Melting point: 183-184 ° CC ₃₃ H ₃ - | CIN ₄ 0 (M = 535.09) calc .: Mol peak (M + H) +: 535/537 found: Mol peak (M + H) +: 535/537

Rr value: 0.66 (silica gel, dichloromethane / ethanol 10: 1) Example 1.29 7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [c [1 2,3] triazin-4-on

1.29. a 7- (4-chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [o] [1, 2,3] triazin-4-on

Prepared analogously to Example 1.18.a from 4'-chloro-3-amino-biphenyl-4-carboxylic acid

{2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide.

Yield: 0.21 g (68.7% of theory)

Melting point: 265-266 ° C

C ₃₃ H ₃ - | CIN4O2 (M = 551, 09) calc .: Mol peak (M + H) +: 551/553 found: Mol peak (M + H) +: 551/553

Rr value: 0.53 (silica gel, dichloromethane / ethanol 10: 1)

Example 1.30 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-benzo [d] [1 , 2,3] triazin-4-one

1.30.a 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-benzo [d] [ 1, 2,3] triazin-4-one

Prepared analogously to Example 1.18.a from 4'-chloro-3-amino-biphenyl-4-carboxylic acid

{2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -amide.

Yield: 0.14 g (54.9% of theory)

Melting point: 165-166 ° C

C ₃₂ H ₃₅ CIN ₄ O (M = 527.11) calc .: Mol peak (M + H) +: 527 found: Mol peak (M + H) +: 527

Rr value: 0.56 (silica gel, dichloromethane / ethanol 10: 1) Example 1.31:

6- (4-chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2H-isoquinolin-1-one

1.31.a. 2- [2- (4-Bromo-phenyl) -ethoxy] -tetrahydropyran To a solution of 4.83 g (24.02 mmol) of 2- (4-bromo-phenyl) -ethanol in 12 ml of dichloromethane are added 0 ° C successively added 0.025 g of p-Tolouolsulfonsäure and 2.575 ml (28.22 mmol) of dihydropyran. Subsequently, the reaction mixture is stirred for three hours at room temperature. The

Reaction mixture is extracted with sodium bicarbonate solution and the organic phase dried over sodium sulfate. The purification is carried out by column chromatography on Alox (eluent: cyclohexane / ethyl acetate = 8: 2). Yield: 37 g (32.8% of theory) of Cι ₃ Hι ₇ Br0 (M = 285.18) calc .: Mole peak (M) +: 284/286 found: Molpeak (M) +: 284/286

1.31.b 4- [2- (Tetrahydropyran-2-yloxy) ethyl] benzaldehyde

To a solution of 5 g (17.53 mmol) of 2- [2- (4-bromo-phenyl) -ethoxy] -tetrahydropyran in 80 ml of tetrahydrofuran at -70 ° C 11, 5 ml (18.41 mmol ) was added dropwise to a 1, 6 M n-butyllithium and stirred for one hour at this temperature. Subsequently, 2.8 ml (36.46 mmol) of dimethylformamide are added dropwise and the reaction mixture is stirred at -70 ° C for two hours. The reaction mixture is treated with ammonium chloride solution and extracted with ethyl acetate. The combined organic phases are extracted three times with saturated sodium chloride solution and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: cyclohexane / ethyl acetate = 6: 4). Yield: 2.8 g (68.2% of theory) C- | ₄ H ₁₈ 0 ₃ (M = 234.29) calc .: Mol peak (M + H) +: 235 found: Mol peak (M + H) +: 235

Rr value: 0.57 (silica gel, petroleum ether / ethyl acetate 3: 1)

1.31.c 4- (2-Hydroxyethyl) benzaldehyde

A solution of 2.8 g (11.95 mmol) of 4- [2- (tetrahydropyran-2-yloxy) ethyl] benzaldehyde in a mixture of 48 ml of 1 M hydrochloric acid and 60 ml of acetone is kept at 5 for 5 hours ° C stirred. The reaction mixture is treated with 140 ml of saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic phases are extracted three times with water and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: cyclohexane / ethyl acetate = 1: 1). Yield: 1.3 g (72.4% of theory) CgH ₁₀ O ₂ (M = 150.17) calc .: Mol peak (M + H) +: 151 found: Mol peak (M + H) +: 151

Rr value: 0.52 (silica gel, petroleum ether / ethyl acetate 1: 1) '

ber.: Molpeak (M+H)+: 209 gef.: Molpeak (M+H)+: 2091.31.d 2- (4- [1,3] dioxan-2-yl-phenyl) -ethanol A suspension of 9.4 g (62.59 mmol) of 4- (2-hydroxy-ethyl) -benzaldehyde, 15, 83 ml (219.07 mmol) of 1, 3-propanediol, 0.3 g of p-toluenesulfonic acid and 150 ml of toluene is heated to reflux for three hours. The reaction mixture is extracted three times with saturated sodium bicarbonate solution and the organic phase is dried over sodium sulfate. Yield: 8 g (61, 4% of theory)

Calc .: Molpeak (M + H) +: 209 Found: Molepeak (M + H) +: 209

1.31.e Methanesulfonic acid 2- (4- [1,3] dioxan-2-yl-phenyl) -ethyl ester 8 g (38.41 mmol) of 2- (4- [1,3] dioxan-2-yl) phenyl) -ethanol and 10.65 ml (42.25 mmol) of triethylamine are dissolved in 300 ml of dichloromethane and at 0 ° C with 3.27 ml of methanesulfonyl chloride, dissolved in 50 ml of dichloromethane. The reaction mixture is stirred for one hour at room temperature, three times with Extracted water and the organic phase dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 1: 1). Yield: 7.7 g (70% of theory) C ₁₃ H ₁₈ O ₅ S (M = 286.34) calc .: Mol peak (M + H) +: 287 found: Mol peak (M + H) +: 287

R _f value: 0.49 (silica gel, petroleum ether / ethyl acetate 1: 1)

1.31.f (E) -3- (3-Bromo-phenyl) -acryloylazide To a solution of 25 g (111, 1 mmol) of (E) -3- (3-bromo-phenyl) -acrylic acid and 15.26 ml (110.10 mmol) of triethylamine in 800 ml of acetone are added dropwise at 0 ° C 11, 5 ml (121, 11 mmol) of ethyl chloroformate. After one hour, 11.5 g (176.16 mmol) of sodium azide dissolved in 88 ml of distilled water are likewise added dropwise at 0 ° C. The reaction mixture is allowed to warm to room temperature and then poured onto 1, 3 I of ice water. The precipitate is filtered off, washed with water and dried in a convection oven at 30 ° C. Yield: 21.1 g (76.1% of theory) CgH ₆ BrN ₃ O (M = 252.07) calc .: Mol peak (M + H) +: 256/258 found: Mol peak (M + H) +: 256/258

R _f value: 0.85 (silica gel, petroleum ether / ethyl acetate 1: 1)

1.31.g 6-Bromo-2H-isoquinolin-1-one

150 g of biphenyl ether and 7.08 ml (29.75 mmol) of tributylamine are heated to 100 ° C. At this temperature, 5 g (19.83 mmol) of (E) -3- (3-bromo-phenyl) - acryloyl azide are added and then heated to 195-205 ° C for two hours.

Thereafter, the reaction mixture is allowed to cool and pours cooled in n-

Hexane. The precipitate is filtered off and treated with a mixture of cooled n-

Washed hexane and diethyl ether. Subsequently, the solid is dried in a circulating air dryer at 50 ° C. The solid is stirred with a mixture of diisopropyl ether and ethyl acetate and the

Drying process repeated.

Yield: 0.6 g (13.5% of theory) CgH ₆ BrN ₃ O (M = 224.05) calc .: Mol peak (M + H) +: 224/226 found: Mol peak (M + H) +: 224/226

1.31.h 6- (4-Chloro-phenyl) -2H-isoquinolin-1-one A reaction mixture of 0.57 g (2.54 mmol) of 6-bromo-2 / - / - isoquinolin-1-one, 0.398 g (2.54 mmol) of 4-chlorophenylboronic acid, 2.6 ml of a 2M sodium carbonate solution in 20 ml of dioxane and 5 ml of methanol is heated to 110 ° C in the microwave for two hours. Subsequently, the reaction mixture is poured into water, the precipitate is filtered off and dried in a convection oven at 40 ° C.

Yield: 0.42 g (64.6% of theory) Cι ₅ Hι ₀ CINO (M = 255,70) calc .: molecular peak (M + H) +: 256/258 Found .: molecular peak (M + H) +: 256/258

Rr value: 0.6 (silica gel, dichloromethane / ethanol 10: 1)

1.31.i 2- [2- (4-Formyl-phenyl) -ethyl] -6- (4-chloro-phenyl) -2H-isoquinolin-1-one A solution of 0.41 g (1.6 mmol) of 6 - (4-chloro-phenyl) -2 -isoquinolin-1-one in 10 ml of dimethylformamide is mixed with 0.18 g (1, 6 mmol) of potassium tert-butylate and stirred at 50 ° C for 30 minutes. Subsequently, the addition of 0.46 g (1, 6 mmol) of methanesulfonic acid 2- (4- [1, 3] dioxan-2-yl-phenyl) -ethyl ester. The

Reaction mixture is heated for five hours at 180 ° C in the microwave and then poured onto a 10% citric acid solution. It is extracted with ethyl acetate. The organic phase is extracted three times with water and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: petroleum ether / Essigsäue ethyl ester = 3: 1 to 1: 1).

Yield: 0.15 g (24.1% of theory) C24H1 ₈ CIN0 (M = 387.87) calc .: Mol peak (M + H) +: 388/390 found: mol peak (M + H) +: 388/390 R _f value: 0.7 (silica gel, petroether / ethyl acetate 1: 1)

1.31.j 6- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2H-isoquinolin-1-one 0.14 g (0.36 mmol) of 2- [2- (4-formyl-phenyl) -ethyl] -6- (4-chloro-phenyl) -2H-isoquinolin-1-one and 0.03 ml (0 , 36 mmol) of pyrrolidine are dissolved in 40 ml of dichloromethane. With glacial acetic acid, a pH of three is set. Subsequently, 0.076 g (0.36 mmol) of sodium triacetoxyborohydride are added and stirred for 48 hours at room temperature. Thereafter, the reaction mixture is extracted with 2M sodium carbonate solution and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluent: dichloromethane / ethanol 10: 1 to 1: 1). Yield: 0.04 g (25% of theory) Melting point: 136-137 ° C

C-28 27 ^CIN 2 ° < ^{M = 442} >") Calc .: Mol peak (M + H) +: 443 Found: Mol peak (M + H) +: 443

Rr value: 0.5 (silica gel, dichloromethane / methanol 10: 1)

The following compounds are prepared analogously to Examples 1.1 to 1.31:

Example 2.1:

4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.1.a 4'-chloro-biphenyl-4-carboxylic acid

5.83 g (29.0 mmol) of 4-bromo-benzoic acid are dissolved in 50 ml of dioxane and 29 ml of 2M sodium carbonate solution. 4.5 g (29.0 mmol) of 4-chlorophenylboronic acid and 1.68 g (1.45 mmol) of tetrakis (triphenylphosphine) palladium are added successively and the reaction is refluxed for 6 hours. The hot reaction solution is filtered through a glass fiber filter. The filtrate is extracted with ethyl acetate. The aqueous phase is acidified with citric acid and stirred for one hour at 0 ° C. The resulting precipitate is filtered off, washed with water and dried in vacuo. Yield: 5.1 g (75.6% of theory) C- | ₃ HgCl ₂ (M = 232,668) calc .: Mol peak (MH) ": 231/233 found: Mol peak (MH)": 231/233.

2.1.b. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

To a suspension of 251 mg (1.08 mmol) 4'-chlorobiphenyl-4-carboxylic acid in

At room temperature, 5 mL of THF are added at room temperature to 471 mg (1.47 mmol) TBTU and 0.26 mL (1.47 mmol) Hünigbase. The reaction mixture is stirred for 10 minutes and then 200 mg (0.98 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (see Example 1.1.h) are added. The mixture is stirred overnight. The reaction solution is mixed with saturated NaHC0 ₃ solution, the aqueous phase extracted with ethyl acetate and the organic phase dried over magnesium sulfate. The solvent is distilled off on a rotary evaporator and the residue is stirred with fe / t-butylmethyl ether with heating. The resulting Solid is filtered off, washed with a little tert-butyl methyl ether and at the

Air dried.

Yield: 210 mg (51.2% of theory)

C ₂ 6H27CIN ₂ 0 (M = 418.971) calc .: molecular peak (M + H) +: 419/421 Found .: molecular peak (M + H) +: 419/421

Rr value: 0.57 (silica gel, dichloromethane / methanol / acetic acid 9: 1: 0.1).

Example 2.2:

4'-chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

2.2. a (4-diethylaminomethyl-phenyl) -acetonitrile

0.88 mL (8.38 mmol) of diethylamine is dissolved in 30 mL of acetone, and 2.1 g (15.2 mmol) of potassium carbonate and 1.6 g (7.62 mmol) of (4-bromomethylphenyl) -acetonitrile (see 1.1.f) are added in succession. The reaction mixture is stirred for 2 h at room temperature, filtered through a glass frit and washed with ethyl acetate. The filtrate is concentrated on a rotary evaporator, extracted with water and ethyl acetate. The organic phase is dried over magnesium sulfate and the solvent removed on a rotary evaporator. Further purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol 9: 1). Yield: 900 mg (58.4% of theory) C _{| 3} Hι. ₈ N ₂ (M = 202.30) calc .: Mol peak (M + H) +: 203 found: Mol peak (M + H) ⁺ : 203 R _f value: 0.65 (silica gel, dichloromethane / methanol 9: 1) , 2.2.b. 2- (4-diethylaminomethyl-phenyl) -ethylamine

A solution of 900 mg (4.45 mmol) of (4-diethylaminomethyl-phenyl) -acetonitrile in

20 mL methanolic ammonia solution is mixed with 100 mg Raney nickel and shaken at 50 ° C and 5 bar in an autoclave. After aspirating the

Catalyst, the solvent is removed on a rotary evaporator.

Yield: 900 mg (98.0% of theory)

C- | ₃ H22N ₂ (M = 206,334) calc .: Mol peak (M + H) +: 207 found: Mol peak (M + H) +: 207

Rr value: 0.12 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

2.2.c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 2.1.b from 4'-chlorobiphenyl-4-carboxylic acid (248 mg, 1.07 mmol) and 2- (4-diethylaminomethyl-phenyl) -ethylamine (200 mg, 0.97 mmol). Yield: 280 mg (68.6% of theory) C-26 29 ^CIN 2θ (M = 420.987) calc .: Mol peak (M + H) +: 421/423 Found: Mol peak (M + H) +: 421 / 423

Rr value: 0.49 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.3:

4'-chloro-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide

2.3.a. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared analogously to Example 2.1. b from 4'-chlorobiphenyl-4-carboxylic acid (234 mg,

1.01 mmol) and 2- (4-piperidin-1-ylmethyl-phenyl) -ethylamine (see 1.15.b, 200 mg,

0.92 mmol).

Yield: 260 mg (65.6% of theory)

^C 27 ^H 29 ^CIN 2θ (M = 432.998) calc .: Mol peak (M + H) +: 433/435 Found: Mol peak (M + H) +: 433/435

Rr value: 0.57 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.4: 4'-Methoxy-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

2.4.a 1 - (4'-methoxy-biphenyl-4-yl) -ethanone

To a solution of 11.3 g (85.0 mmol) of aluminum chloride in 100 mL of carbon disulfide is added 4-methoxybiphenyl. The mixture is warmed to 40 ° C and then very slowly with 6.07 ml (81.4 mmol) of acetyl chloride. The reaction is refluxed for one hour. After cooling, the reaction solution to 100 g of ice and 25 mL conc. Hydrochloric acid. After extraction with dichloromethane, the organic phase is dried over magnesium sulfate. The solvent is removed on a rotary evaporator and the residue is recrystallized from isopropanol. Yield: 8.8 g (48.0% of theory) C- | 5H- | ₄ 0 ₂ (M = 226.278) calc .: Mol peak (M + H) +: 227 found: Mol peak (M + H) +: 227

2.4.b 4'-methoxy-biphenyl-4-carboxylic acid To a solution of 15.6 g (390.9 mmol) of NaOH in 70 mL of water is added dropwise at 0 ° C 6.0 mL (117 mmol) of bromine slowly. Then add slowly 8.8 g (39.1 mmol) of 1- (4'-methoxy-biphenyl-4-yl) -ethanone in 50 ml of dioxane. After three hours, the solid formed is filtered off, taken up in dichloromethane and filtered again. The filtrate is freed from the solvent on a rotary evaporator.

Yield: 9.0 g (100.0% of theory) C ₁₅ H ₄ O ₂ (M = 228.250) calc .: Mol peak (MH) ^" : 227 F: Mol peak (MH) ^" : 227

2.4.c 4'-Methoxy-biphenyl-4-carboxylic acid chloride

A solution of 3.0 g (0.013 mol) of 4'-methoxy-biphenyl-4-carboxylic acid in 47.4 mL (0.65 mol) of thionyl chloride is stirred at 50 ° C for three hours. After removal of thionyl chloride on a rotary evaporator, the product is obtained as a yellowish solid, which is stored in the refrigerator. Yield: 3.2 g (99.8% of theory) Ci5H- | ₄ 0 ₂ (M = 246,696) calc .: Mol peak (M + H) +: 246/248 found: Mol peak (M + H) +: 246/248.

2.4.d 4'-Methoxy-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide

To a solution of 200 mg (0.97 mmol) 2- (4-diethylaminomethyl-phenyl) -ethylamine and 0.25 mL (1.45 mmol) Hünig base in 5 mL dichloromethane is added at 0 ° C 287 mg (1.16 mmol) acid chloride. The reaction is stirred overnight and then treated with half-saturated NaHC0 ₃ solution. The aqueous phase is washed with dichloromethane and the combined organic phase dried over Magnesiumsuifat. After removal of the solvent on a rotary evaporator, the residue is triturated with fetϊ-butylmethyl ether and the resulting solid is filtered off with suction. Yield: 90 mg (22.3% of theory) C27H ₃₂ N ₂ O ₂ (M = 416,568) calc .: Mol peak (M + H) +: 417 F: Mol peak (M + H) +: 417. Rr value: 0.46 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.5.

4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amide

2.5. a [2- (4-diethylaminomethyl-phenyl) -ethyl] -carbamic acid-tert-butyl ester

To a solution of 700 mg (3.93 mmol) 2- (4-diethylaminomethylphenyl) ethylamine in 5.0 mL dichloromethane and 0.52 mL (3.73 mmol) triethylamine is added 815 mg (3.73 mmol) BOC anhydride and stirred at room temperature overnight , The mixture is mixed with saturated NaHC0 ₃ solution. The aqueous phase is washed with dichloromethane and the organic phase dried over magnesium sulfate. After removal of the solvent on a rotary evaporator, the residue is purified by column chromatography on silica gel (eluent: dichloromethane / methanol / NH ₃ = 9: 1: 0.1). Yield: 600 mg (57.7% of theory) C | ₈ H ₃₀ N ₂ O ₂ (M = 306.452) calc .: Mol peak (M + H) +: 307 Found: Mol peak (M + H) +: 307.

2.5. b [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amine To a suspension of 250 mg (6.59 mmol) of lithium aluminum hydride in 10 mL of tetrahydrofuran is slowly added 600 mg (1.96 mmol) of [2- (4-diethylaminomethyl - phenyl) -ethyl] -carbaminsäure terf-butyl ester in THF was added dropwise. The reaction is stirred overnight and heated to 50 ° C for an additional hour. Work-up is carried out by successive addition of 0.25 mL water, 0.25 mL 15% NaOH solution and 0.75 mL water. After filtration, the organic phase is over Dried magnesium sulfate and the solvent removed on a rotary evaporator.

Yield: 350 mg (81.1% of theory)

C ₁₄ H ₂₄ N ₂ (M = 220.361) calc .: Mol peak (M + H) +: 221 found: Mol peak (M + H) +: 221.

2.5.C 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amide

Prepared analogously to Example 2.1.b from 4'-chlorobiphenyl-4-carboxylic acid (222 mg, 0.95 mmol) and [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amine (175 mg, 0.79 mmol).

Yield: 60 mg (17.4% of theory) C ₂ 7H ₃₁ CIN ₂ O (M = 435.014) calc .: Mole peak (M + H) +: 435/437 F: Mol peak (M + H) +: 435/437 R _f value: 0.39 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.6:

2.6.a. 4- (4-Chloro-phenyl) -cyclohexanecarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 4- (4-chlorophenyl) -cyclohexanecarboxylic acid (239 mg, 1.0 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (204 mg, 1.0 mmol).

Yield: 65 mg (15.3% of theory) C ₂ 6H ₃₃ CIN ₂ O (M = 425.019) calc .: Mol peak (M + H) +: 425/427 found: Mol peak (M + H) +: 425/427

Rr value: 0.3 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.7:

4-piperidin-1-yl-Λ- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.7.a Ethyl 4-piperidine-1-yl-benzoate To a suspension of 0.5 mL (4.13 mmol) of ethyl 4-fluoro-benzoate and 571 mg (4.13 mmol) of potassium carbonate in 20 mL of DMSO is added 0.41 mL of piperidine. The reaction mixture is stirred at 70 ° C overnight, added more 1 mL (2.44 mmol) piperidine and stirred at 70 ° C for a further 6 h. After filtration, water is added, the mixture is extracted with ethyl acetate, the organic phase is separated off and the solvent is removed on a rotary evaporator. The product is further reacted without purification. Yield: 706 mg (73.2% of theory) C ₁₄ H ₁₉ N0 ₂ (M = 233.313) calc .: Mol peak (M + H) +: 234 F: Mol peak (M + H) +: 234 retention time HPLC : 6.2 min (method A)

2.7.b 4-piperidine-1-yl-benzoic acid

ber.: Molpeak (M+H)+: 206 gef.: Molpeak (M+H)+: 206To a solution of 350 mg (1.50 mmol) of ethyl 4-piperidin-1-yl-benzoate in 10 mL of ethanol is added 0.78 mL (0.74 mmol) 2N NaOH. The reaction solution is stirred for 2 h at 60 ° C and then the pH is adjusted to 6-7 with 1 N HCl. The resulting precipitate is dried after filtration under high vacuum overnight. Yield: 158 mg (51.3% of theory)

Calc .: Mol peak (M + H) +: 206 Found: Mol peak (M + H) +: 206

Retention time HPLC: 6.2 min (method A)

2.7.c 4-Piperidine-1-yl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (157 mg, 0.77 mmol) and 4-piperidin-1-yl-benzoic acid (158 mg, 0.77 mmol).

Yield: 102 mg (33.8% of theory)

C ₂ 5H33N ₃ 0 (M = 391, 561) calc .: Mol peak (M + H) +: 392 found: Mol peak (M + H) +: 392

Retention time HPLC: 4.4 min (method A)

Example 2.8:

2.8.a 4-Benzyl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared by the general procedure I described at the outset from diphenylmethane-4-carboxylic acid (104 mg, 0.49 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (100 mg, 0.49 mmol). Yield: 66 mg (33.9% of theory) C 27 H ₃ rjN ₂ O (M = 398.553) calc .: Mol peak (M + H) +: 399 F: Mol peak (M + H) +: 399

Rr value: 0.46 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.9:

4- (4-Oxo-cyclohexylidenemethyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.9.a 4- (1,4-dioxa-spiro [4.5] dec-8-ylidenemethyl) -benzoic acid ethyl ester To a solution of 90.0 mL (0.63 mol) of diisopropylamine in 100 mL of THF at -20 ° C is added 350 mL ( 0.56 mol, 1.6 M in hexane) n-BuLi solution was added dropwise and the reaction solution was stirred at -20 ° C for 30 min. 112 g (0.37 mol) of ethyl 4- (diethoxy-phosphorylmethyl) benzoate in 100 ml of THF are slowly added dropwise. The reaction solution is stirred at -20 ° C. for 1 h and then 58 g (0.37 mol) of 1,4-dioxa-spiro [4.5] decan-8-one in 200 ml of THF are added dropwise. The reaction solution is stirred for 30 min at -12 ° C and then warmed to room temperature over 2 h. It is mixed with water, the aqueous phase extracted with ether, ethyl acetate and dichloromethane. The organic phase is filtered through silica gel. After removal of the solvent on a rotary evaporator, the residue is purified by chromatography (silica gel, petroleum ether / ethyl acetate 9: 1). Yield: 80 g (72.0% of theory).

2.9.b 4- (1,4-dioxa-spiro [4.5] dec-8-ylidenemethyl) benzoic acid

20 g of NaOH in 130 ml of water are added to a solution of 35 g (0.12 mol) of 4- (1,4-dioxa-spiro [4.5] dec-8-ylidenemethyl) -benzoic acid ethyl ester in 150 ml of ethanol, and the mixture 2 cooked at reflux. The reaction solution is concentrated to 400 g of ice and 60 mL conc. Hydrochloric acid, the aqueous phase extracted with ethyl acetate and the solvent removed on a rotary evaporator. Yield: 32 g (91.4% of theory). Melting point: 164-165 ° C.

2.9.C 4- (4-Oxo-cyclohexylidenemethyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 4- (1,4-dioxaspiro [4.5] dec-8-ylidenemethyl) benzoic acid (134 mg, 0.49 mmol) and 2- (4-pyrrolidin-1-ylmethylphenyl) - ethylamine (100mg, 0.49mmol). Yield: 57 mg (28.0% of theory) of C ₂ H 7H ₃₂ N ₂ O ₂ (M = 416,568) calc .: Mole peak (M + H) +: 417 F: Mol peak (M + H) +: 417

Rr value: 0.36 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.10:

2.10.a 4- (4-Oxo-cyclohexyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 4- (4-oxo-cyclohexyl ) - benzoic acid (128 mg, 0.49 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (100 mg, 0.49 mmol). Yield: 26 mg (13.1% of theory) C ₂ 6H ₃ 2N ₂ 0 ₂ (M = 404.557) calc .: Mol peak (M + H) +: 405 F: Mol peak (M + H) +: 405 R _f value: 0.31 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.11:

4-Cyclohexyl-1-cyclohexylcarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

ber.: Molpeak (M-H)": 209 gef.: Molpeak (M-H)": 2092.11.a 4-Cyclohexyl-1-cyclohexylcarboxylic acid To a solution of 500 mg (2.10 mmol) of 4- (4-chlorophenyl) -cyclohexanecarboxylic acid in 10 mL of methanol is added 0.44 mL of conc. Hydrochloric acid and 100 mg of platinum oxide. The reaction mixture is stirred at 50 ° C and 5 bar hydrogen for 3 h. After separation of the catalyst, the solvent is removed on a rotary evaporator. Yield: 440 mg (99.9% of theory)

Calc .: Molpeak (MH) ": 209 Found: Molepeak (MH)": 209

2.11.b 4-Cyclohexyl-1-cyclohexylcarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from bicyclohexyl-4-carboxylic acid (103 mg, 0.49 mmol) and 2- (4-pyrrolidin-1-ylmethylphenyl) ethylamine (100mg, 0.49mmol). Yield: 2.0 mg (1.0% of theory) C2δH ₄ oN ₂ O (M = 396.622) calc .: Mol peak (M + H) +: 397 F: Mol peak (M + H) +: 397

Rr value: 0.46 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.12:

2.12.a 4-Methylphenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to the general procedure II described above from 4-methylphenyl-piperidine (175 mg, 1.0 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (204 mg, 1.0 mmol). Yield: 90.0 mg (22.2% of theory) C 26 H 35 N ₃ O (M = 405.558) calc .: Mol peak (M + H) +: 406 F: Mol peak (M + H) +: 406

Rr value: 0.30 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.13:

4- (4-Chloro-phenyl) -3,6-dihydro-2H-pyridine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.13.a 4- (4-Chloro-phenyl) -1,2,3,6-tetrahydro-pyridine

To 100 mL (1.2 mol) of formalin solution (37% in water) and 32.1 g (0.6 mol) of ammonium chloride is added dropwise at 60 ° C 4-chloro-methylstyrene. The

Reaction mixture is stirred for 3 h at 60 ° C and then cooled to room temperature. 100 mL of methanol are added and the mixture is stirred overnight. After evaporation of the solvent on a rotary evaporator, the residue with 150 mL of conc. Hydrochloric acid and stirred for 4 h at 1O0 ° C. After cooling to room temperature, it is poured onto ice and made alkaline with NaOH pellets. After multiple extraction with ether, the organic phase is dried over sodium sulfate. After removal of the solvent on a rotary evaporator, the residue is passed through Column chromatography on silica gel (eluent: ethyl acetate: methanol: NH ₃ 9: 1: 0.1).

Yield: 17.0 g (29.3% of theory)

C- | - | H _{| |} 2CIN (M = 193,678) calc .: Mol peak (M + H) +: 194 found: Mol peak (M + H) +: 194

Rr value: 0.26 (silica gel, ethyl acetate / methanol / NH ₃ 6: 4: 0.4).

13.2. b 4- (4-Chloro-phenyl) -3,6-dihydro-2H-pyridine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure II from 4- (4-chloro-phenyl) -1,2,3,6-tetrahydropyridine (193 mg, 1.0 mmol) and 2- (4-pyrrolidin-1-ylmethylphenyl) -ethylamine (204 mg, 1.0 mmol). Yield: 40.0 mg (9.4% of theory) of C ₂ H 5 H ₃₀ CIN ₃ O (M = 423.990) calc .: Mole peak (M + H) +: 424/426 Found: Molepeak (M + H) +: 424/426

Rr value: 0.30 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.14:

2.14.a 3,4,5,6-Tetrahydro-2H- [4,4 '] bipyridinyl-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 1, 2,3,4,5, 6-hexahydro [4,4 '] bipyridinyl (81 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethylphenyl) - ethylamine (102 mg, 0.50 mmol). Yield: 43.8 mg (22.3% of theory) C24H ₃₂ N ₄ O (M = 392.549) calc .: Mol peak (M + H) +: 393 F f: Mol peak (M + H) +: 393 R f value: 0.14 (Silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1). Example 2.15:

2.15.a 4-Benzyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-benzyl-piperidine (87.7 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 33.5 mg (16.5% of theory.) C26 3δN θ ₃ (M = 405.6) calc .: molecular peak (M + H) +: 406. Found .: molecular peak (M + H) +: 406

Rr value: 0.36 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.16:

2.16.a 4- (1H-indol-3-yl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 3-piperidin-4-yl-1H-indole

(100 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg,

0.50 mmol). Yield: 56.5 mg (26.2% of theory)

C27H34N ₄ O (M = 430.6) calc .: Mol peak (M + H) +: 431 Found: Mol peak (M + H) +: 431 Rr value: 0.36 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.17:

ber.: Molpeak (M+H)+: 499 gef.: Molpeak (M+H)⁺: 4992.17.a 1 '- [2- (4-Pyrrolidin-1-ylmethyl-phenyl) -ethylcarbamoyl] - [4,4'] bipiperidinyl-1-carboxylic acid tert-butyl ester Prepared according to general procedure II of [4, 4 '] - Bipiperidinyl-1-carboxylic acid tert-butyl ester (134 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 51.0 mg (20.5% of theory)

Calc .: Molpeak (M + H) +: 499 Found: Molepeak (M + H) ⁺ : 499

Rr value: 0.40 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.18:

4-Cyclohexyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.18.a 4-cyclohexyl-piperidine

To a solution of 1.0 g (6.4 mmol) of 4-phenylpyridine in 20 mL of methanol is added 1.35 mL of conc. Hydrochloric acid and 200 mg of platinum oxide. The reaction mixture is stirred at 50 ° C and 3 bar hydrogen for 2.5 h. After separation of the catalyst, the solvent is removed on a rotary evaporator, wherein the product precipitates as the hydrochloride. Yield: 1.2 (91, 4% of theory) C _{1 1} H ₂ ιN * HCl (M = 203.,758) calc .: Mol peak (M + H) +: 168 F: Mol peak (M + H) +: 168.

2.18.b 4-Cyclohexyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-cyclohexyl-piperidine (83.7 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 38.0 mg (19.1% theory d.) C 5 H _{3 3} 0 gN (M = 397.6) calc .: molecular peak (M + H) +: 398 Found .: molecular peak (M + H) +: 398

Rr value: 0.54 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.19: 4- (4-Chloro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.19.a 4- (4-Chloro-phenyl) -piperidine To a solution of 5.0 g (21.7 mmol) 4- (4-chloro-phenyl) -1, 2,3,6-tetrahydropyridine (see 2.13.a ) in 20 mL of methanol is added 500 mg Pd / C. The

Reaction mixture is stirred at room temperature and 10 psi hydrogen for 7 h.

After separation of the catalyst, the solvent is on

Rotary evaporator removed. Further purification is carried out by column chromatography on silica gel (eluent: dichloromethane / methanol / ammonia

= 5: 4.9: 0.1).

Yield: 3.2 (75.3% of theory)

-C - _| H ₁₄ CIN (M = 195,694) calc .: Molpeak (M + H) +: 196/198 found: Molpeak (M + H) +: 196/198. Rf value: 0.37 (silica gel, dichloromethane / methanol / NH ₃ 5: 4.9: 0.1). 2.19.b 4- (4-Chloro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

ber.: Molpeak (M+H)+: 426/428 gef.: Molpeak (M+H)+: 426/428 Rf-Wert: 0.49 (Kieselgel, Essigester/Methanol/NH₃ 9:1 :0.1).Prepared according to general procedure II from 4- (4-chlorophenyl) piperidine (97.9 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 9.0 mg (4.2% of theory)

Calc .: Molpeak (M + H) +: 426/428 Found: Molepeak (M + H) +: 426/428 Rf value: 0.49 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.20:

20.2. a 4-Hydroxy-4- (4-trifluoromethyl-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-hydroxy-4- (4-trifluoromethyl-phenyl) -piperidine (123 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 35.0 mg (14.7% of theory) ^C 26 ^H 32 ^F 3N ₃ O ₂ (M = 475.6) calc .: Mol peak (M + H) +: 476 F: Mol peak (M + H) +: 476

Rr value: 0.45 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.21:

2.21.a 3-Phenyl-8-aza-bicyclo[3.2.1]octan-8-carbonsäure-[2-(4-pyrrolidin-1 - ylmethyl-phenyl)-ethyl]-amid

2.21.a 3-Phenyl-8-aza-bicyclo [3.2.1] octane-8-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 3-phenyl-8-azabicyclo [3.2.1] octane (93.7 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 26.0 mg (12.5% of theory) C ₂ 7H ₃₅ N ₃ O (M = 417.6) calc .: Mole peak (M + H) +: 418 F: Mol peak (M + H) +: 418 Rf Value: 0.51 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.22:

2.22.a 4- (4-Chloro-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4- (4-chlorophenyl) -piperazine (117 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 13.0 mg (6.1% of theory) C24H ₃ - | CIN ₄ 0 (M = 427.0) calc .: Mol peak (M + H) +: 427/429 found: Mol peak (M + H) +: 427 / 429

R value: 0.42 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.23:

2.23.a 4-Cyan-4-phenyl-piperidin-1 -carbonsäure-[2-(4-pyrrolidin-1 -ylmethyl- phenyl)-ethyl]-amid

2.23.a 4-cyano-4-phenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-cyano-4-phenyl-piperidine (111 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 27.0 mg (13.0% of theory) C26H32N ₄ θ (M = 416.6) calc .: Mole peak (M + H) +: 417 m.p .: Mol peak (M + H) +: 417 R _f value: 0.46 (m.p. Silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.24:

2.24. a 3-aza-spiro [5.5] undecane-3-carboxylic acid [2- (4-pyrrolidin-1-yl-methyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 3-aza-spiro [5.5] undecane (76.7 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 24.0 mg (12.5% of theory) C ₂ H ₃₇ N ₃ O (M = 383.6) calc .: Mole peak (M + H) +: 384 F: Mol peak (M + H) +: 384

Rr value: 0.49 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.25:

2.25.a 4-(4-Fluor-phenyl)-piperidin-1 -carbonsäure-[2-(4-pyrrolidin-1 -ylmethyl- phenyl)-ethyl]-amid

2.25.a 4- (4-Fluoro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4- (4-fluoro-phenyl) -piperidine (108 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 32.0 mg (15.6% of theory) C25H32FN ₃ O (M = 409.6)

Calc .: Mol peak (M + H) +: 410 Found: Mol peak (M + H) +: 410 R _f value: 0.50 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.26:

2.26.a 1,2-Dihydro-1- (methylsulfonyl) -spiro [3H-indole-3,4'-piperidine] -1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure II from 1,2-dihydro-1- (methylsulfonyl) -spiro [3H-indole-3,4'-piperidine] (133.2 mg, 0.50 mmol) and 2- (4-pyrrolidin-1 -ylmethyl-phenyl) -ethylamine (102mg, 0.50mmol). Yield: 28.0 mg (11.3% of theory.) C-27H ₃ 6N ₄ 0 ₃ S (M = 496.7) calc .: molecular peak (M + H) +: 497 Found .: molecular peak (M + H) +: 497

Rr value: 0.42 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1). Example 2.27:

2.27.a 4- (4-chloro-phenyl) -4-hydroxy-piperidine-1 -carboxylic acid [2- (4-pyrrolidin-1 ^■ ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4- (4-chlorophenyl) -4-hydroxy-piperidine (106 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 32.0 mg (14.5% of theory) C25H ₃₂ CIN ₃ 0 ₂ (M = 442.0) calc .: Mol peak (M + H) +: 442/444 found: Mol peak (M + H) +: 442/444

Rr value: 0.44 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.28:

2.28.a 4- (4-Methoxy-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4- (4-methoxyphenyl) -piperazine (133 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine

(102 mg, 0.50 mmol).

Yield: 35.0 mg (16.6% of theory) C25H ₃₄ N ₄ 0 ₂ (M = 422.6) calc .: Mol peak (M + H) +: 423 F: Mol peak (M + H) +: 423

Rr value: 0.47 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1). Example 2.29:

2.29. 4- (2-Methoxy-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4- (2-methoxyphenyl) piperidine (114 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 20.0 mg (9.5% of theory) C ₂ 6H35N ₃ 0 ₂ (M = 421.6) calc .: Mol peak (M + H) +: 422 F: Mol peak (M + H) +: 422

Rr value: 0.55 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.30:

2.30.a 1,3-Dihydro-isoindole-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 1,3,3-dihydro-isoindole (77.8 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 13.0 mg (7.4% of theory)

C ₂ 2H27N ₃ 0 (M = 349.48) calc .: Mol peak (M + H) +: 350 F: Mol peak (M + H) +: 350 Rr value: 0.30 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.31:

2.31.a 1, 2,4,5-Tetrahydro-benzo [azepine-3-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 1, 2,4,5-tetrahydrobenzo [d] azepine (73.6 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol). Yield: 12.0 mg (6.4% of theory) C ₄ H ₃ ιN ₃ O (M = 377.534) calc .: Mole peak (M + H) +: 378 F: Mol peak (M + H) +: 378 Rf- Value: 0.33 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.32:

2.32.a 4-Phenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-phenyl-piperidine (80.6 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol).

Yield: 24.0 mg (12.3% of theory) C 25 H ₃₃ N ₃ O (M = 391, 561) calc .: Mole peak (M + H) +: 392 F: Mol peak (M + H) +: 392 Rr value: 0.35 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.33:

4- (4-Dimethylaminomethyl-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.33. a 4- (4-Dimethylaminomethyl-phenyl) -4-hydroxy-piperidine-1-carboxylic acid-fer-butyl ester To a solution of 81 g (0.38 mol) 4-bromodimethylbenzylamine in 450 mL THF at -65 ° C 236 mL (0.38 mol, 1.6M in hexane) n-BuLi was added dropwise over 35 min. 75 g (0.38 mol) of tetra-4-oxo-piperidine-1-carboxylate in 150 ml of THF are added dropwise over 60 minutes, so that the temperature does not exceed -60 °. The reaction solution is stirred at -65 ° C. for 2 h and at room temperature for a further 17 h. The reaction mixture is mixed with 300 mL of ether, cooled to 5 ° C and the resulting precipitate was filtered off with suction. 200 ml of water and 700 ml of ether are added to the precipitate and the mixture is stirred for 10 minutes. The organic phase is dried over magnesium sulfate and the solvent removed on a rotary evaporator. The resulting product is dried in vacuo. Yield: 45 g (35.7% of theory)

2.33.b Dimethyl- [4- (1,2,3,6-tetrahydro-pyridin-4-yl) -benzyl] -amine

70 ml of trifluoroacetic acid are added dropwise at -10 ° C. to a solution of 45 g (0.14 mol) of tert-butyl 4- (4-dimethylaminomethyl-phenyl) -4-hydroxy-piperidine-1-carboxylate in 140 ml of dichloromethane. The solution is added for 1.5 h

Stirred room temperature, cooled to -10 ° C and 30 mL conc. Sulfuric acid added. After half an hour, add another 10 mL of sulfuric acid. After 1 h, the solvent is removed on a rotary evaporator and added to 300 g of ice. With 6 N NaOH solution, the pH is adjusted to 14. The aqueous phase is saturated with potassium carbonate and washed twice Ether extracted. The combined organic phases are evaporated to dryness on a rotary evaporator. Yield: 25.2 g (86.9%)

2.33.C Dimethyl (4-piperidin-4-yl-benzyl) -amine

To a solution of 16 g (74 mmol) of dimethyl [4- (1,2,3,6-tetrahydropyridin-4-yl) benzyl] amine in 200 mL of methanol is added 6 g of Pd / BaSO. The solution is stirred for 1 h at room temperature in a hydrogen atmosphere, the catalyst is filtered off and the solvent is removed on a rotary evaporator. The residue is dissolved in methanol, methanolic hydrochloric acid added and then treated with ether until cloudy. After storage at -20 ° C, the resulting hydrochloride is filtered off with suction. Yield: 16 g (84.9%).

2.33.d 4- (4-Dimethylaminomethyl-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure II of 4- (4- Dimethylaminomethyl-phenyl) -piperidine (127mg, 0.50mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102mg, 0.50mmol). Yield: 37.0 mg (16.5% of theory) C ₂₈ H ₄₀ N ₄ O (M = 448.657) calc .: Mole peak (M + H) +: 449 F: Mol peak (M + H) +: 449

Rr value: 0.37 (silica gel, dichloromethane / methanol / NH ₃ 9: 1: 0.1).

Example 2.34:

4'-chloro-biphenyl-4-yl) - [3- (4-pyrrolidin-1-ylmethyl-phenyl) -piperidin-1-yl] -methanone

2.34.a 1 - (4-Bromo-benzyl) -pyrrolidine

20.0 g (0.080 mol) of 4-bromobenzyl bromide in THF are slowly added dropwise to a solution of 13.1 ml (0.16 mmol) of pyrrolidine and 200 ml of tetrahydrofuran so that the temperature does not exceed 20.degree. The reaction solution is stirred overnight and, after mixing with ice, acidified with concentrated hydrochloric acid. After extraction with ether, the aqueous phase is made alkaline with sodium hydroxide solution and saturated with potassium carbonate. After extraction with ether, the organic phase is dried over magnesium sulfate and the solvent is removed on a rotary evaporator. Yield: 18.1 g (94.2% of theory) C | -I Hι ₄ BrN (M = 240.145) calc .: Mol peak (M + H) +: 240/242 Found: Mol peak (M + H) +: 240/242

Rr value: 0.19 (silica gel, petroleum ether / ethyl acetate 8: 2).

2.34. b 3- (4-pyrrolidin-1-ylmethyl-phenyl) -pyridine

1.11 g (4.64 mmol) of 1- (4-bromo-benzyl) -pyrrolidine is dissolved in 10 mL dioxane and 5 mL

2M sodium carbonate solution dissolved. Successively, 570 mg (4.64 mmol) of pyridine-3-boronic acid and 270 mg (0.23 mmol) of tetrakis (triphenylphosphine) - palladium are added and the reaction is refluxed for 6 h. The reaction solution is filtered with suction through a glass fiber filter. The filtrate is extracted several times with ethyl acetate. The organic phase is dried over magnesium sulfate and the solvent removed on a rotary evaporator. Further purification is carried out by column chromatography on silica gel (eluant: ethyl acetate / methanol / NH ₃ = 8: 2: 0.1). Yield: 500 mg (45.2% of theory) C ₁₆ H ₈ N ₂ (M = 238.335) calc .: Mol peak (M + H) +: 239 found: Mol peak (M + H) +: 239

2.34.C 3- (4-Pyrrolidin-1-ylmethyl-phenyl) -piperidine To a solution of 500 mg (2.10 mmol) of 3- (4-pyrrolidin-1-ylmethyl-phenyl) -pyridine in 10 ml of ethanol is added 4 mL 1 M hydrochloric acid and 200 mg platinum oxide. The reaction mixture is stirred at room temperature and 3 bar of hydrogen for 4.5 h. After separation of the catalyst, the solvent is removed on a rotary evaporator, wherein the product precipitates as the hydrochloride. Yield: 600 mg (100% of theory) of C ₆ H ₂₄ N ₂ ^* HCl (M = 280.844) calc .: Mol peak (M + H) +: 245 F: Mol peak (M + H) +: 245.

2.34.d (4'-Chloro-biphenyl-4-yl) - [3- (4-pyrrolidin-1-ylmethyl-phenyl) -piperidin-1-yl] -methanone

Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (183 mg, 0.78 mmol) and 3- (4-pyrrolidin-1-ylmethyl-phenyl) -piperidine

(200 mg, 0.71 mmol).

Yield: 20.0 mg (6.1% of theory) C ₂ gH ₃₁ CIN ₂ O (M = 459.036) calc .: Mol peak (M + H) +: 459/461 found: Mol peak (M + H) +: 459 / 461

Rr value: 0.58 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.35:

4'-Chloro-biphenyl-4-carboxylic acid [2-methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide

2.35. a 2-Methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propionitrile

To a solution of 2.0 g (10.0 mmol) of (4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile

(see 1.1.g) in 50 ml of tetrahydrofuran are added 3.4 g (30 mmol) of potassium tert-butoxide at room temperature. The reaction solution is stirred briefly, treated with 1.9 mL (30 mmol) of methyl iodide, stirred for a further 2 h at room temperature and then on

Rotary evaporator evaporated to dryness. The backlog will be between

Water and ethyl acetate are distributed, the organic phase washed with water and dried over magnesium sulfate. The solvent is dissolved on

Removed rotary evaporator and the crude product reacted further without purification.

Yield: 1.4 g (61.3% of theory)

C ₁₅ H ₂ O N ₂ (M = 228.340) calc .: Mol peak (M + H) +: 229 F: Mol peak (M + H) +: 229

Rr value: 0.40 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.35. b 2-Methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propylamine

To a solution of 1.4 g (6.13 mmol) of 2-methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propionitrile in 20 ml of methanolic ammonia solution is added 150 mg of Raney nickel. The reaction mixture is stirred overnight at 50 ° C and 5 bar hydrogen atmosphere. After filtering off the catalyst, the solvent is removed on a rotary evaporator. Yield: 1.4 g (98.3% of theory) of C 5 H ₂₄ N ₂ (M = 232.372) calc .: Mole peak (M + H) +: 233 F: Mol peak (M + H) +: 233 Rr value: 0.30 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.35.C. 4'-Chloro-biphenyl-4-carboxylic acid [2-methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide

Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (233 mg, 1.0 mmol) and 2-methyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -propylamine (232 mg, 1.0 mmol ).

Yield: 400 mg (89.5% of theory)

C ₂₈ H ₃₁ CIN ₂ O (M = 447.025) calc .: Mol peak (M + H) +: 447/449 found: Mol peak (M + H) +: 447/449

R _f value: 0.35 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.36: 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide

2.36.a 2- (4-pyrrolidin-1-ylmethyl-phenyl) -propionitrile

To a solution of 2.0 g (10.0 mmol) (4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile (see 1.1.g) in 50 ml of tetrahydrofuran is added at room temperature 1.12 g (10 mmol) of potassium fer-butylate. The reaction solution is stirred for 30 min and then admixed with 0.63 ml (10 mmol) of methyl iodide. The reaction is stirred for 1 h at 50 ° C and then evaporated on a rotary evaporator to dryness. The residue is partitioned between water and ethyl acetate, the organic phase is washed twice with water and dried over magnesium sulfate. The solvent is stripped off on a rotary evaporator and the crude product, which contains about 20% of the dimethylated compound, is reacted further without purification. Yield: 0.5 g (23.3% of theory) C ₁₄ H ₈ N ₂ (M = 214.313) calc .: Mol peak (M + H) +: 215 F: Mol peak (M + H) +: 215

Rr value: 0.40 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.36.b 2- (4-Pyrrolidin-1-ylmethyl-phenyl) -propylamine To a solution of 400 mg (1.87 mmol) 2- (4-pyrrolidin-1-ylmethyl-phenyl) -propionitrile in 20 ml methanolic ammonia solution Add 100 mg of Raney nickel. The reaction mixture is stirred overnight at 50 ° C and 5 bar hydrogen atmosphere. After filtering off the catalyst, the solvent is removed on a rotary evaporator. The amine containing about 20% dimethylated compound is reacted further without further purification. Yield: 0.4 g (98.6% of theory) C ₁₅ H 22 N ₂ (M = 218.345) calc .: Mol peak (M + H) +: 219 F: Mol peak (M + H) +: 219

Rr value: 0.30 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.36.C 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (233mg, 1.0mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -propylamine (218mg, 1.0mmol). Yield: 10 mg (2.3% of theory) C ₈ H ₃ - | CIN ₂ O (M = 447.025) calc .: Mol peak (M + H) +: 447/449 Found: Mol peak (M + H) +: 447/449

Rr value: 0.35 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1);

Example 2.37:

4'-chloro-biphenyl-4-carboxylic acid (4-pyrrolidin-1-ylmethyl-benzyloxy) -amide

2.37.a 2- (4-Pyrrolidin-1-ylmethyl-benzyloxy) -isoindole-1,3-dione A solution of 13.2 g (50 mmol) of α, α'-dibromo-p-xylene in 125 ml of acetonitrile is added At room temperature, a mixture of 8.2 g (50 mmol) of Λ / -hydroxy- phthalimide and 8.7 mL (50 mmol) Hünig base in 125 mL acetonitrile. The reaction solution is stirred for 10 min, then add 4.1 mL (50 mmol) of pyrrolidine and stirred for an additional hour. After filtration, the mother liquor is concentrated on a rotary evaporator to dryness. The residue is purified by chromatography on silica gel (eluent:

Essigester / methanol / ammonia). The substance was immediately reacted after cleaning.

Yield: 1.0 g (5.9% of theory)

Rr value: 0.60 (Alox, ethyl acetate / petroleum ether 1: 1).

2.37.b <L (4-pyrrolidin-1-ylmethyl-benzyl) -hydroxylamine To a solution of 1.0 g (2.97 mmol) 2- (4-pyrrolidin-1-ylmethyl-benzyloxy) -isoindol-1,3-dione in 50 mL of toluene are added 50 mL of 40% methylamine solution in water and the mixture is stirred for 2.5 days at room temperature. After separation of the organic phase, the aqueous phase is extracted twice with te / t-butylmethyl ether. The combined organic phases are washed with water and dried over magnesium sulfate. The solvent is removed on a rotary evaporator and the resulting product is further reacted without purification. Yield: 260 mg (42.4% of theory) of C ₂ H ₈ N ₂ O (M = 206.290) Calc .: Molpeak (M + H) +: 207 Found: Molepeak (M + H) +: 207.

ber.: Molpeak (M+H)+: 421/423 gef.: Molpeak (M+H)+: 421/4232.37.C 4'-Chloro-biphenyl-4-carboxylic acid (4-pyrrolidin-1-ylmethyl-benzyloxy) -amide Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (116 mg, 0.5 mmol ) and 0- (4-pyrrolidin-1-ylmethyl-benzyl) -hydroxylamine (103 mg, 0.5 mmol). Yield: 10.0 mg (4.8% of theory)

Calc.: Molpeak (M + H) +: 421/423 Found: Molepeak (M + H) +: 421/423

Rr value: 0.38 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.38:

4'-Chloro-biphenyl-4-carboxylic acid [1, 1-dimethyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.38. a (4-pyrrolidin-1-ylmethyl-phenyl) -acetic acid ethyl ester

3.0 g (15 mmol) of (4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile (see 1.1 g) is dissolved in ethanolic hydrochloric acid (saturated) and heated under reflux for 4 hours. The solvent is removed on a rotary evaporator and the residue is taken up in dilute NaHCO ₃ solution and fer-butyl methyl ether. The organic phase is dried with sodium sulfate, filtered with suction through activated charcoal and then the solvent is removed on a rotary evaporator. Yield: 3.4 g (91.6% of theory) C15H21N0 ₂ (M = 247.340) calc .: Mole peak (M + H) +: 248 F: Mol peak (M + H) +: 248 Rr value: 0.25 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.38. b 2-Methyl-1- (4-pyrrolidin-1-ylmethyl-phenyl) -propan-2-ol 3.4 g (13.8 mmol) are added dropwise at room temperature to 13.3 ml (40 mmol) of a 3.0 M methylmagnesium chloride solution in tetrahydrofuran. (4-Pyrrolidin-1-ylmethyl-phenyl) -acetic acid ethyl ester in 20 mL tetrahydrofuran. The temperature rises to 40 ° C. The reaction mixture is stirred for one hour and then poured onto 100 mL ammonium chloride solution. The aqueous phase is extracted several times with dichloromethane. The combined organic phases are washed with saturated sodium chloride solution and dried over magnesium sulfate. The solvent is removed on a rotary evaporator and the residue is purified by column chromatography on Alox (activity 2-3) (eluent: cyclohexane: ethyl acetate 4: 1). Yield: 800 mg (24.9% of theory) C- | 5H ₂₃ NO (M = 233.357) calc .: Mol peak (M + H) +: 234 found: Mol peak (M + H) +: 234

Rf value: 0.50 (Alox, petroleum ether / ethyl acetate 6: 4).

2.38.C Λ / - [1, 1-Dimethyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -formamide To a solution of 250 mg (5.0 mmol) of sodium cyanide in 2 mL of glacial acetic acid is added a mixture of 2 mL sulfuric acid and 1 ml of glacial acetic acid added dropwise so that the temperature of the reaction mixture does not exceed 20 ° C. Then, 800 mg (3.43 mmol) of 2-methyl-1- (4-pyrrolidin-1-ylmethyl-phenyl) propan-2-ol are added dropwise in 2 mL of glacial acetic acid. The temperature is kept below 20 ° C. The reaction solution is stirred for one hour at room temperature and then poured onto ice and neutralized with sodium carbonate solution. The aqueous phase is extracted with ether and the organic phase is dried over magnesium sulfate. The solvent is removed on a rotary evaporator and the product is reacted further without purification. Yield: 520 mg (58.2% of theory) Cl 6 ^H 24 ^N 2 O (M = 260,382) calc .: Mol peak (M + H) +: 261 F: Mol peak (M + H) +: 261. 2.38. d. 1,1-Dimethyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine. To a solution of 520 mg (2 mmol) / V- [1,1-dimethyl-2- (4-pyrrolidin-1-) ylmethyl-phenyl) -ethyl] -formamide in 10 ml of ethanol is added 25 ml of conc. Hydrochloric acid and heated overnight at reflux. After cooling the reaction solution is made alkaline with 25% aqueous sodium hydroxide solution and the aqueous phase extracted several times with tert-butyl methyl ether. The combined organic phases are washed with water, dried over magnesium sulfate and filtered through activated charcoal. The solvent is removed on a rotary evaporator. Yield: 380 mg (81.8% of theory) Cj 5H ₂₄ N ₂ (M = 232.372) calc .: Mol peak (M + H) +: 233 F: Mol peak (M + H) +: 233

Rr value: 0.10 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

2.38.e 4'-Chloro-biphenyl-4-carboxylic acid [1, 1 -dimethyl-2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (116 mg, 0.5 mmol) and 1, 1-dimethyl-2- (4-pyrrolidin-1-ylmethylphenyl) -ethylamine (116 mg, 0.5 mmol).

Yield: 73.0 mg (32.7% of theory) C ₂₈ H ₃ 1 CIN ₂ 0 ₂ (M = 447.025) calc .: Mole peak (M + H) +: 447/449 found: mol peak (M + H) +: 447/449

Rr value: 0.48 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.39: 4'-Chloro-biphenyl-4-carboxylic acid 4- (2-pyrrolidin-1-yl-ethyl) -benzylamide

2.39. a 4- (2-pyrrolidin-1-yl-ethyl) -benzonitrile

To a solution of 500 mg (2.74 mmol) 4- (2-aminoethyl) benzonitrile in 50 mL acetonitrile is added successively 91 mg (0.56 mmol) potassium iodide, 453 mg (3.28 mmol). Potassium carbonate and 0.33 mL (2.74 mmol) of 1,4-dibromobutane were added. The reaction is stirred at 78 ° C for 6h. Another 0.08 mL (0.66 mmol) of 1, 4-dibromobutane are added and the reaction is stirred overnight at 78 ° C. After filtration, the filtrate is evaporated to dryness. Further purification is carried out by column chromatography on silica gel (dichloromethane / methanol 8: 2). Yield: 183.0 mg (33.4% of theory) C- | ₃ H ₁₆ N ₂ (M = 200.286) calc .: Mol peak (M + H) +: 201 Found: Mol peak (M + H) +: 201.

2.39.b 4- (2-pyrrolidin-1-yl-ethyl) -benzylamine

To a solution of 183 mg (0.91 mmol) of 4- (2-pyrrolidin-1-yl-ethyl) -benzonitrile in 20 mL ethanolic ammonia solution is added 75 mg of Raney nickel. The reaction solution is stirred at 50 ° C and 3 bar of hydrogen overnight. Another 75 mg of Raney nickel are added and stirring is continued for a further 6 h at 50 ° C. and 3 bar of hydrogen.

The catalyst is filtered off and the solvent is removed on a rotary evaporator. The crude product can be used without further purification. Yield: 114.0 mg (61.0% of theory) C ₁₃ H ₂ oN ₂ (M = 204.318) calc .: Mol peak (M + H) +: 205 F: Mol peak (M + H) +: 205.

2.39.C 4'-Chloro-biphenyl-4-carboxylic acid 4- (2-pyrrolidin-1-yl-ethyl) -benzylamide Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (130 mg, 0.56 mmol) and 4- (2-pyrrolidin-1-yl-ethyl) -benzylamine (114 mg, 0.56 mmol).

Yield: 75.0 mg (32.1% of theory) C26H27CIN2O (M = 418.971) calc .: Mol peak (M + H) +: 419/421 Found: Mol peak (M + H) +: 419/421

Rr value: 0.38 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1). Example 2.40:

2.40.a [1, 4 '] bipiperidinyl-1'-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-piperidinopiperidine

(84.1 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg,

0.50 mmol).

Yield: 3.0 mg (1.5% of theory)

C24H ₃₈ N ₄ O (M = 398.597) calc .: Mol peak (0.5M + H) +: 200 Found: Mol peak (0.5M + H) +: 200

Retention time HPLC: 1.59 min (Method A)

Example 2.41:

2.41.a 4-Cyclohexyl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 4-cyclohexylbenzoic acid (102 mg, 0.50 mmol) and 4- ( 2-pyrrolidin-1-yl-ethyl) -benzylamine (102 mg, 0.50 mmol).

ber.: Molpeak (M+H)+: 391 gef.: Molpeak (M+H)+: 391 RrWert: 0.38 (Kieselgel, Essigester/Methanol/N H₃ 9:1 :0.1).Yield: 2.0 mg (1.0% of theory)

Calc .: Mol peak (M + H) +: 391 Found: Mol peak (M + H) +: 391 Rr value: 0.38 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1).

Example 2.42:

4'-chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-cyclohexyl) -ethyl] -amide

2.42.a 2- (4-pyrrolidin-1-ylmethylcyclohexyl) ethylamine

To a solution of 500 mg (2.45 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (see Example 1.1.h) in 10 mL of methanol is added 1.52 mL of conc. Hydrochloric acid and 300 mg of platinum oxide. The reaction mixture is stirred at 50 ° C and 5 bar hydrogen for 50 h. After separation of the catalyst, the solvent is removed on a rotary evaporator. Further purification is carried out by column chromatography on silica gel (dichloromethane / methanol / ammonia 8: 2: 0.2). Yield: 130 mg (25.3% of theory) ^C 13 ^H 26 ^N ₂ (M = 210.366) calc .: Mol peak (M + H) +: 211 F: Mol peak (M + H) +: 211

Rr value: 0.14 (silica gel, dichloromethane / methanol / NH ₃ 8: 2: 0.2).

2.42.b 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-cyclohexyl) -ethyl] -amide

Prepared according to general procedure I from 4'-chlorobiphenyl-4-carboxylic acid (116 mg, 0.50 mmol) and 2- (4-pyrrolidin-1-ylmethylcyclohexyl) ethylamine (105 mg, 0.50 mmol). Yield: 53.0 mg (24.9% of theory)

^C 26 ^H 33CIN ₂ O (M = 425.019) calc .: Mol peak (M + H) +: 425/427 found: Mol peak (M + H) +: 425/427

Rr value: 0.16 (silica gel, ethyl acetate / methanol / NH ₃ 9: 1: 0.1). Example 2.43: 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.43. a 4-cyanomethyl-2-methoxy-benzoic acid Prepared analogously to Example 1.1.d from 4-cyanomethyl-2-methoxy-benzoic acid methyl ester. Yield: 6.5 g (69.8% of theory) C | ₀ HgNO ₃ (M = 191, 18) calc .: Mol peak (M + H) +: 192 _F : Mol peak (M + H) +: 192 R _f value: 0.64 (silica gel, dichloromethane / ethanol 10: 1) ,

2.43. b (4-hydroxymethyl-3-methoxy-phenyl) -acetonitrile Prepared analogously to Example 1.1. e from 4-cyanomethyl-2-methoxy-benzoic acid. Yield: 4.81 g (81% of theory) of C ₁₀ H 1 NO ₂ (M = 177.20) calc .: Mole peak (M) +: 177 F: Mol peak (M) +: 177.

2.43.C (4-bromomethyl-3-methoxyphenyl) -acetonitrile Prepared analogously to Example 1.1.f from (4-hydroxymethyl-3-methoxyphenyl) acetonitrile

Yield: 4.2 g (64.6% of theory.) C ₁₀ Hι ₀ BrNO (M = 240.10) calc .: molecular peak (M) +: 239/241 Found .: molecular peak (M) +: 239 / 241

Rf value: 0.84 (silica gel, dichloromethane / ethanol 50: 1).

2.43.d (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile

Prepared analogously to Example 1.1. g of (4-bromomethyl-3-methoxyphenyl) acetonitrile and piperidine. Yield: 0.95 g (24.2% of theory) of Cι ₄ Hι ₈ N ₂ O (M = 230.31) calc .: Mol peak (M + H) +: 231 found: Molpeak (M + H) +: 231.

2.43. e (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine

Prepared analogously to Example 1.1. h from (3-methoxy-4-pyrrolidin-1-ylmethylphenyl) acetonitrile. The crude product is immediately reacted without purification.

2.43.f 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 2- (3-methoxy-4-pyrrolidine

1 -ylmethyl-phenyh-ethylamine and 4'-chloro-biphenyl-4-carboxylic acid.

Yield: 0.5 g (86.2% of theory)

Melting point: 162-163 ° C C27H29CIN2O2 (M = 448.99) calc .: Mol peak (M + H) +: 449/451 Found: Mol peak (M + H) +: 449/451

Rr value: 0.85 (silica gel, dichloromethane / ethanol / ammonia 5: 1: 0.1).

Example 2.44: 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-fluoro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.44.a (£) -3- (4-Cyano-2-fluoro-phenyl) -acrylic acid To a solution of 20.0 g (100 mmol) 4-bromo-3-fluoro-benzonitrile in 200 mL DMF are added 2.75 g (10 mmol) of palladium acetate and 7.0 g (25 mmol) of tri-otolylphosphane. Then 50 mL of triethylamine and 30 mL (30 mmol) of ethyl acrylate are added. The reaction mixture is stirred for 3 h at 100 ° C, diluted after cooling with 400 mL of dichloromethane and twice with water washed. The solvent is removed on a rotary evaporator and the residue taken up in 250 ml of methanol while heating. Insolubles are removed by suction through kieselguhr and the filtrate is concentrated in half on a rotary evaporator. After repeated filtration, 150 ml of THF, 100 ml of MeOH and 43 ml of 2N NaOH are added and the mixture is stirred at room temperature for 2 h. The solvent is removed on a rotary evaporator and the residue is mixed with 100 ml of water. After extraction with ether, the aqueous phase is acidified with conc. Hydrochloric acid acidified. The precipitated crystals are dissolved in 300 ml of warm ethyl acetate, the water phase is separated. The ethyl acetate is distilled off and the resulting crystals are slurried with ether and filtered with suction. Yield: 11.5 g (60.2% of theory) Melting point: 214-218 ° C.

2.44.b 3- (4-Cyano-2-fluoro-phenyl) -propionic acid

A solution of 11.5 g (60 mmol) of (ε) -3- (4-cyano-2-fluorophenyl) -acrylic acid in 200 ml of water is mixed with 4.0 g of 5% Pd / C and 24.4 g of potassium carbonate. The mixture is shaken for 6 h at room temperature and normal pressure hydrogen in an autoclave. After aspirating the catalyst, the mother liquor with conc. Hydrochloric acid acidified. The precipitated crystals are dissolved in 250 ml of warm ethyl acetate, dried and the ethyl acetate distilled off. The resulting crystals are stirred with ether / hexane and filtered with suction. Yield: 900 mg (98.0% of theory) Melting point: 102-106 ° C.

2.44.C [2- (4-Cyano-2-fluoro-phenyl) -ethyl] -carbamic acid tert-butyl ester To a solution of 500 mg (2.6 mmol) of 3- (4-cyano-2-fluoro-phenyl ) -propionic acid in 5 mL tetf-butanol are added 1.25 mL triethylamine and 0.61 mL (2.8 mmol) diphenylphosphoryl azide. The reaction mixture is refluxed overnight and then the solvent is removed on a rotary evaporator. Purification is carried out by column chromatography on silica gel (dichloromethane / methanol 9: 1). Yield: 138 mg (20.2% of theory) of CI ₇ FN ₂ O ₂ (M = 264.302) Calc .: Molpeak (M + H) +: 265 Found: Molepeak (M + H) +: 265

2.44. d [2- (4-Aminomethyl-2-fluoro-phenyl) -ethyl] -carbamic acid-ferf-butyl ester A solution of 138 mg (0.52 mmol) of [2- (4-cyano-2-fluoro-phenyl) - ethyl] -carbamic acid-tert-butyl ester in 15 mL ethanolic ammonia solution is mixed with 75 mg Raney nickel and the mixture is shaken overnight at 50 ° C and 3 bar hydrogen in an autoclave. After aspirating the catalyst, the solvent is removed on a rotary evaporator. Yield: 137 mg (97.8% of theory) of CI H ₂ ι FN 0 ₂ (M = 268.334) calc .: Mole peak (M + H) +: 269 F: Mol peak (M + H) +: 269.

2.44. e [2- (2-Fluoro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -carbamic acid fe / -butyl ester To a solution of 300 mg (1.12 mmol) of [2- (4-aminomethyl-2-fluoro -phenyl) - ethyl] -carbamic acid-tert-butyl ester in 15 mL acetonitrile is added successively 42 mg (0.25 mmol) potassium iodide, 180 mg (1.30 mmol) potassium carbonate and 0.13 mL (1.11 mmol) 1, 4-dibromobutane. The reaction is stirred at 78 ° C for 6h. Another 0.08 mL (0.66 mmol) of 1, 4-dibromobutane are added and the reaction is stirred overnight at 78 ° C. The solvent is removed on a rotary evaporator and the product is reacted further without purification. Yield: 320 mg (88.8% of theory) C | ₈ H ₂ FN ₂ θ2 (M = 322.426) calc .: molecular peak (M + H) +: 323 Found .: molecular peak (M + H) +: 323rd

2.44.f 2- (2-Fluoro-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine To a solution of 232 mg (0.72 mmol) of [2- (2-fluoro-4-pyrrolidin-1-yl-methylphenyl) ethyl] -carbamic acid-fe / t-butyl ester in 5 mL dichloromethane is added to 1.5 mL trifluoroacetic acid. The reaction mixture is stirred for 2 h at room temperature. The solvent is removed on a rotary evaporator and the crude product is further reacted without purification. Yield: 160 mg (100% of theory) C ₁₃ H ₉ FN ₂ (M = 222.308) Calc .: Molpeak (M + H) +: 223 Found: Molepeak (M + H) +: 223.

2.44.g 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-fluoro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 2- (2-fluoro 4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (160 mg, 0.72 mmol) and 4'-chlorobiphenyl-4-carboxylic acid (168 mg, 0.72 mmol). Yield: 49 mg (15.6% of theory) C26 26 ^CIFN 2θ (= 436.961) calc.: Mole peak (M + H) +: 437/439. : Molepeak (M + H) +: 437/439

Retention time HPLC: 6.6 min (method A)

Example 2.45:

4-pyridin-4-yl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.45a. 4-pyridin-4-yl-benzoic acid methyl ester

3.0 g (15 mmol) 4-bromo-pyridine is dissolved in 50 mL dioxane and 15 mL 2M

Dissolved sodium carbonate solution. 2.7 g (15 mmol) of 4-methoxycarbonylphenylboronic acid and 1.73 g (2 mmol) of tetrakis are successively added.

(Triphenylphosphine) palladium added and the reaction was refluxed for 6 h. The hot reaction solution is filtered through a glass fiber filter. The solvent is removed on a rotary evaporator and the purification is carried out by column chromatography on silica gel (dichloromethane / methanol 9: 1). Yield: 845 mg (26.4% of theory) of C ₁₃ H- | iN0 ₂ (M = 213.238) calc .: Mol peak (M + H) +: 214 found: Mol peak (M + H) +: 214

Retention time HPLC: 4.1 min (Method A) 2.45b. 4-pyridin-4-yl-benzoic acid

To a solution of 150 mg (0.70 mmol) 4-pyridin-4-yl-benzoic acid methyl ester in 10 mL ethanol 0.37 mL (0.74 mmol) 2N NaOH are added. The reaction solution is stirred for 2 h at 60 ° C and then with 1N HCl the pH is adjusted to 6-7. The resulting precipitate is dried after filtration under high vacuum overnight. Yield: 84 mg (60.0% of theory) C ₁ H 9 NO ₂ (= 199,211) Calculated: Mol peak (M + H) +: 200 F: Mol peak (M + H) +: 200 Retention time HPLC: 2.5 min (Method A)

2.45c. 4-Pyridin-4-yl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) ethylamine (86 mg, 0.42 mmol) and 4-pyridin-4-yl-benzoic acid (84 mg, 0.42 mmol).

Yield: 65 mg (40.0% of theory) C ₂ 5H ₂ 7N ₃ O (M = 385.513) calc .: Mol peak (M + H) +: 386 F: Mol peak (M + H) +: 386

Retention time HPLC: 4.7 min (Stable Bond C18, 3.5 μm, water: acetonitrile: formic acid 91: 9: 0.01).

Example 2.46:

5- (4-chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2,3-dihydro-isoindol-1-one

2.46.a 4-bromo-2-methyl-benzoic acid ethyl ester

A solution of 5.0 g (23.3 mmol) of 4-bromo-2-methylbenzoic acid in 50 ml of ethanolic hydrochloric acid is stirred at 45 ° C. for 8 h. The reaction solution is cooled overnight to room temperature and then the solvent on Rotary evaporator removed. The residue is taken up in ether, filtered and the solvent removed on a rotary evaporator. The residue is reacted further without purification. Rf value: 0.88 (silica gel, dichloromethane / ethanol 95: 5).

2.46.b 4'-Chloro-3-methyl-biphenyl-4-carboxylic acid ethyl ester 1.66 g (6.83 mmol) of ethyl 4-bromo-2-methylbenzoate are dissolved in 70 ml of dioxane and 7 ml of 2M sodium carbonate solution. Successively, 1.07 g (6.83 mmol) of 4-chloro-phenyl-boronic acid and 0.40 g (0.34 mmol) of tetrakis (triphenylphosphine) palladium are added, the reaction is refluxed for 6 h and the mixture is stirred at room temperature for a further 60 h. The hot reaction solution is filtered through a glass fiber filter. The solvent is removed on a rotary evaporator. The residue is mixed with water and the aqueous phase extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and the solvent removed on a rotary evaporator. The purification is carried out by column chromatography on silica gel (petroleum ether / ethyl acetate 8: 2). Yield: 1.3 g (69.3% of theory) of C ₁ H ₆ H ₁₅ ClO 2 (M = 274.750) calc .: Mole peak (M + H) +: 275/277 m.p .: Mol peak (M + H) +: 275/277

Rr value: 0.67 (silica gel, petroleum ether / ethyl acetate 8: 2).

2.46.C 3-Bromomethyl-4'-chloro-biphenyl-4-carboxylic acid ethyl ester

To a solution of 1.3 g (4.73 mmol) of 4'-chloro-3-methyl-biphenyl-4-carboxylic acid ethyl ester and 0.84 g (4.73 mmol) of N-bromosuccinimide in 10 mL

Carbon tetrachloride is charged with 78 mg (0.47 mmol) of 2,2-azobis (isobutyronitrile). The reaction mixture is refluxed overnight. After filtration, the solvent is concentrated on a rotary evaporator. The purification is carried out by column chromatography on silica gel (petroleum ether / ethyl acetate 8: 2).

Yield: 1.6 g (62.1% of theory) of Cι ₆ Hι ₄ BrCl _{2 2} (M = 353,646) calc .: Mol peak (M + H) +: 353/355/357 F: Mol peak (M + H) + : 353/355/357 R _f value: 0.57 (silica gel, petroleum ether / ethyl acetate 8: 2).

2.46.d 5- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -2,3-dihydroisoindol-1-one To a suspension of 800 mg (1.47 mmol) of ethyl 3-bromomethyl-4'-chlorobiphenyl-4-carboxylate and 508 mg (3.68 mmol) of potassium carbonate in 7.5 ml of acetonitrile at room temperature, 375 mg (1.47 mmol) of 2- (4-pyrrolidine) 1-ylmethyl-phenyl) -ethylamine is slowly added dropwise. The reaction mixture is refluxed for 5 hours. After removal of the solvent on a rotary evaporator, the residue is taken up in water and ethyl acetate. The aqueous phase is extracted with ethyl acetate and the combined organic phases dried over magnesium sulfate. After removal of the solvent on a rotary evaporator, the residue is dissolved in DMF and purified by HPLC chromatography (Stable Bond C18, 3.5 μm, water: acetonitrile: formic acid 9: 1: 0.01 to 1: 9: 0.01 over 9 min). Yield: 82 mg (12.9% of theory) C27H27CIN2O2 (M = 430.982) calc .: Mol peak (M + H) +: 431/433 found: Mol peak (M + H) +: 431/433

Retention time HPLC: 6.13 min (Method A)

Example 2.47:

4-Piperidin-1-ylmethyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.47.a 4-piperidine-1-ylmethylpyridine

To a solution of 100 g (0.61 mol) of 4-chloromethyl-pyridine in 600 ml of dry methanol, 242 ml of piperidine (2.44 mol) are added dropwise and the reaction mixture is stirred at 50 ° C for one hour. The solvent is removed on a rotary evaporator. The residue is made alkaline with 40% sodium hydroxide solution and the aqueous phase extracted with ether. The organic Phase is dried over sodium sulfate and after filtration through activated charcoal, the solvent is removed on a rotary evaporator. The crude product is reacted further without purification. Yield: 106 g (98% of theory)

2.47. b 4-piperidine-1-ylmethyl-piperidine

A solution of 106 g (0.6 mol) of 4-piperidin-1-ylmethyl-pyridine in 1.0 L of glacial acetic acid is mixed with 7 g of platinum dioxide and shaken at room temperature and 3 bar hydrogen in an autoclave. After aspirating the catalyst, the solvent is removed on a rotary evaporator. The crude product is reacted further without purification. Yield: 48 g (43.9% of theory)

2.47.C 4-piperidine-1-ylmethyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 4-piperidine-1-ylmethylpiperidine (182 mg, 1.00 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (204 mg, 1.00 mmol). Yield: 160.0 mg (38.8% of theory) C ₂ 5H ₄₀ N ₄ O (M = 412.624) calc .: Mol peak (M + H) +: 413 F: Mol peak (M + H) +: 413

Retention time HPLC: 1.75 min (Stable Bond C18, 3.5 μm;

Water: acetonitrile: formic acid 9: 1: 0.01 after 4: 6: 0.01 over 8 min).

Example 2.48:

2.48. a 4-(1 H-Benzoimidazol^-y -piperidin-l -carbonsäure-[2-(4-pyrrolidin-1 - ylmethyl-phenyl)-ethyl]-amid

2.48. a 4- (1H-Benzoimidazole) -y-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure II from 2-piperidin-4-yl-1H-benzoimidazole (164 mg, 1.00 mmol) and 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (204 mg, 1.00 mmol).

ber.: Molpeak (M+H)+: 432 gef.: Molpeak (M+H)+: 432Yield: 80.0 mg (18.5% of theory)

Calc .: Molpeak (M + H) +: 432 Found: Molepeak (M + H) +: 432

Retention time HPLC: 2.80 min (Stable Bond C18, 3.5 μm, water acetonitrile formic acid 9: 1: 0.01 after 4: 6: 0.01 over 8 min).

Example 2.49:

4- (1-methyl-piperidin-4-yl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.49.a 4-Piperidin-4-yl-benzoic acid methyl ester

To a solution of 695 mg (3.26 mmol) 4-pyridin-4-yl-benzoic acid methyl ester

(see Example 2.45.a) in 10 mL of ethanol are added 4.0 mL of 1M hydrochloric acid and 200 mg of platinum oxide. The reaction mixture is at room temperature and 3 bar

Hydrogen stirred for 2 h. After renewed addition of 300 mg of platinum oxide and 6.0 mL of 1M hydrochloric acid, stirring was continued for 16 h at room temperature and 3 bar of hydrogen. After separation of the catalyst, the solvent is removed on a rotary evaporator. The crude product is reacted further without purification.

Yield: 589 mg (82.4% of theory) of Cι ₃ Hι N0 ₂ (M = 219.286) calc .: Mol peak (M + H) +: 220 F: Mol peak (M + H) +: 220

Retention time HPLC: 3.5 min (method A) 2.49. b 4- (1-Methyl-piperidin-4-yl) -benzoic acid methyl ester

48 mg (2.00 mmol) of sodium hydride are added in portions to a solution of 429 mg (1.96 mmol) of 4-piperidin-4-yl-benzoic acid methyl ester in 10 mL of DMF under a nitrogen atmosphere at 0 ° C. The

Reaction mixture is stirred for 1 h at room temperature. 0.13 mL (2.10 mmol)

Methyl iodide is added dropwise and the solution is allowed to stand for two hours

Room temperature stirred. The reaction solution is mixed with water, the aqueous phase extracted with ethyl acetate, the combined organic phases dried over magnesium sulfate and the solvent removed on a rotary evaporator. The purification was carried out by column chromatography (silica gel;

Dichloromethane / methanol 8: 2).

Yield: 70 mg (15.3% of theory)

C ₁₄ H ₁₉ N0 ₂ (M = 233.313) calc .: Mol peak (M + H) +: 234 found: Mol peak (M + H) +: 234

Retention time HPLC: 2.7 min (method A)

2.49.C 4- (1-Methyl-piperidin-4-yl) -benzoic acid

0.37 mL (0.74 mmol) 2N NaOH are added to a solution of 70 mg (0.30 mmol) of methyl 4- (1-methyl-piperidin-4-yl) benzoate in 10 mL ethanol.

The reaction solution is stirred for 2 h at 60 ° C and then with 1 N HCl pH on

6-7 set. The resulting precipitate is dried after filtration under high vacuum overnight.

Yield: 50 mg (76.0% of theory) of Ci ₃ H- | ₇ N0 ₂ (M = 219.286) calc .: Mol peak (M + H) +: 220 Found: Mol peak (M + H) +: 220

Retention time HPLC: 1.5 min (method A)

2.49.d 4- (1-Methylpiperidin-4-yl) - / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (47 mg, 0.23 mmol) and 4- (1-methyl-piperidin-4-yl) -benzoic acid (50 mg, 0.23 mmol). Yield: 22 mg (23.8% of theory) ^C 26 35 ^N 3 ° ( ^M = 405.588) calc .: Mole peak (M + H) +: 406 F: Mol peak (M + H) +: 406

Retention time HPLC: 2.4 min (Method A)

Example 2.50:

1.21.a 4'-Chloro-biphenyl-4-carboxylic acid {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -amide Prepared analogously to Example 1.1.i 2- [6- (4-Methyl-piperazin-1-yl) -pyridin-3-yl] -ethylamine and 4'-chlorobiphenyl-4-carboxylic acid. Yield: 0.94 g (96% of theory) Melting point: 211-213 ° C. CC 5H ₂ 7CIN 0 (M = 434.97) Calculated by: Molepeak (M + H) +: 435/437 Found: Molepeak (m.p. M + H) +: 435/437.

Example 2.51: 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (4-methylpiperazine-1-carbonyl) -phenyl] -ethyl} -amide

2.51.a [4-(4-Methyl-piperazin-1-carbonyl)-phenyl]-acetonitriI

2.51.a [4- (4-Methyl-piperazine-1-carbonyl) -phenyl] -acetonitrile

A solution of 2 g (12.41 mmol) of 4-cyanomethylbenzoic acid, 1.25 g (12.5 mmol) of N-methylpiperazine, 4.01 g (12.5 mmol) of TBTU and 3.48 ml (25 mmol ) Triethylamine in 40 ml of DMF is stirred for 12 hours at room temperature. Then the reaction mixture is slightly concentrated and washed with water added. This mixture is extracted with ethyl acetate and the solvent is distilled off on a rotary evaporator. The aqueous phase is also concentrated and combined with the residue of the organic phase. The purification is carried out by column chromatography on silica gel (eluent: dichloromethane / ethanol / ammonia 30: 1: 0.1). Yield: 2.6 g (86% of theory) C | ₄ H ₁₇ N ₃ O (M = 243.31) calc .: Mol peak (M + H) +: 244 found: Mol peak (M + H) +: 244

Rr value: 0.35 (silica gel, dichloromethane / ethanol / ammonia 20: 1: 0.1).

2.51.b [4- (2-Amino-ethyl) -phenyl] - (4-methylpiperazin-1-yl) -methanone Prepared analogously to Example 1.1. i from [4- (4-methylpiperazine-1-carbonyl) phenyl] acetonitrile.

Yield: 2.9 g (90% of theory) C ₁ H ₂ 1 N ₃ 0 x HCI (M = 283.80)

Rr value: 0.25 (silica gel, dichloromethane / ethanol / ammonia 10: 1: 0.1).

2.51.c 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (4-methylpiperazine-1-carbonyl) -phenyl] -ethyl} -amide Prepared according to general procedure I of [4- (4- 2-aminoethyl) - phenyl] - (4-methylpiperazin-1-yl) -methanone and 4'-chlorobiphenyl-4-carboxylic acid. Yield: 0.18 g (48.4% of theory) Melting point: 217-218 ° C C27 28 ^CIN 3 ° 2 (M = 461, 99) calc .: Mole peak (M + H) +: 462/464 .: Molepeak (M + H) +: 462/464

Rr value: 0.25 (silica gel, dichloromethane / methanol / ammonia 10: 1: 0.1).

Example 2.52:

4'-Bromo-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.52a. 4'-bromo-biphenyl-4-carboxylic acid methylester

0.54 g (2.5 mmol) of 4-bromobenzoic acid methyl ester is dissolved in 10 ml of dioxane and 2.5 ml of 2M sodium carbonate solution. Successively, 0.6 g (3 mmol) of 4-bromophenyl boronic acid and 0.12 g (0.1 mmol) of tetrakis (triphenylphosphine) palladium are added and the reaction is refluxed for 5 h. The reaction mixture is treated with water and EtOAc, filtered and the phases are separated. The aqueous phase is extracted with EtOAc 'and the combined organic phases dried over MgS0! After removal of the drying agent and solvent, the residue is triturated with acetonitrile, filtered off with suction and dried in air.

Yield: 100 mg (13.7% of theory) C | ₄ H | | i Br0 ₂ (M = 291, 15) calc .: Mol peak (M + H) +: 291/293 Found: Mol peak (M + H) +: 291/293

Rr value: 0.68 (silica gel, petroleum ether / EtOAc 8: 2).

2.52b. 4'-bromo-biphenyl-4-carboxylic acid

A solution of 100 mg (0.34 mmol) of 4'-bromo-biphenyl-4-carboxylic acid methyl ester in 3 ml of THF is combined with 3 ml of a 1 M NaOH solution in water and heated under reflux for 3 h. The reaction mixture is concentrated in vacuo, the aqueous residue acidified with 1 M HCl, the precipitated

Product filtered off and dried in air.

Yield: 60 mg (63.1% of theory) of Cι ₃ HgBr0 ₂ (M = 277.19) calc .: Mol peak (MH) ": 275/277: Molepeak (MH) ^" : 275/277

Retention time HPLC: 8.48 min (method A)

2.52.C 4'-Bromo-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 45 mg (0.22 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 60 mg (0.22 mmol) of 4'-bromo-biphenyl-4-carboxylic acid.

Yield: 28 mg (27.5% of theory) of C 6 H 27 -BrN ₂ O (M = 463.42) calc .: Mole peak (M + H) +: 463/465 Found: Molepeak (M + H) +: 463 / 465

Retention time HPLC: 6.46 min (Method A)

Example 2.53: 4'-Ethyl-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 113 mg (0.5 mmol) of 4'-ethyl-biphenyl-4-carboxylic acid (Lancaster). Yield: 65 mg (31.5% of theory) C2 ₈ H ₃ 2N 0 (M = 412.58) calc .: Mole peak (M + H) +: 463 F: Mol peak (M + H) +: 463

Retention time HPLC: 6.64 min (method A)

Example 2.54:

Biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 99 mg (0.5 mmol) of biphenyl-4-carboic acid. Yield: 46 mg (23.9% of theory) C26 28 ^N 2 ° ( ^M = 384.53) calc .: Mol peak (M + H) +: 385 found: Mol peak (M + H) +: 385

Retention time HPLC: 5.70 min (method A)

Example 2.55:

4'-fluorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.55a. 4'-fluoro-biphenyl-4-carboxylic acid

14.27 g (71 mmol) of 4-bromo-benzoic acid are dissolved in 120 ml of dioxane and 70 ml of 2M-Na ₂ CO ₃ solution. Successively, 10 g (71 mmol) of 4-fluorophenylboronic acid and 4.1 g (4 mmol) of tetrakis (triphenylphosphine) palladium are added and the reaction is refluxed for 6 hours. The catalyst is filtered off with suction and washed with hot water. EtOAc is added to the reaction mixture, the phases are separated and the aqueous phase acidified with citric acid. The resulting precipitate is filtered off, washed with water and dried at 45 ° C in a vacuum. Yield: 4.9 g (31.9% of theory) of C ₃ H ₉ F0 (M = 216.21) calc .: Mol peak (MH) ^" : 215 F: Mol peak (MH) ^" : 215

2.55b. 4'-Fluorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1 -ylmethyl-phenyl) -ethylamine and 108 mg (0.5 mmol) of 4'-fluorobiphenyl-4-carboxylic acid.

Yield: 12 mg (6.0% of theory.) C26 ^H 27 ^FN 2θ (= 402.52) Calc .: Molpeak (M + H) +: 403 Found: Molepeak (M + H) +: 403

Retention time HPLC: 5.83 min (Method A)

Example 2.56: 4'-Hydroxy-3'-nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 130 mg (0.5 mmol) of 4'-fluoro-3'-nitro-biphenyl-4-carboxylic acid. Yield: 9 mg (4.0% of theory) C ₂ 6H 27 N ₃ O ₄ (M = 445.52) calc.: Mol peak (M + H) +: 446. : Molepeak (M + H) +: 446 Retention time HPLC: 5.83 min (method A)

Example 2.57:

3'-Chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.57a. 3'-chloro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 9.64 g (47.96 mmol) of 4-bromo-benzoic acid and 7.5 g (47.96 mmol) of 3-chlorophenylboronic acid. Yield: 6.2 g (55.6% of theory) C | ₃ H ₉ CI0 ₂ (M = 232.67) calc .: Mol peak (MH) ": 231/233 found: Mol peak (MH)": 231/233 2.57b. 3'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 116 mg (0.5 mmol) of 3'-chlorobiphenyl-4-carboxylic acid.

Yield: 63 mg (30.1% of theory) ^c 26 ^H 27 ^CIN 2 O (M = 418.97) calc .: Mol peak (M + H) +: 419/421 Found: Mol peak (M + H) + : 419/421 Retention time HPLC: 6.20 min (method A)

Example 2.58:

3 ', 4 ^, -dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.58a. 3 ', 4'-dichloro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 5.27 g (26.20 mmol) of 4-bromo-benzoic acid and 5.0 g (26.20 mmol) of 3 ', 4'-dichloro-phenylboronic acid. Yield: 4.05 g (57.9% of theory.) Cι ₃ H ₈ CI ₂ 0 ₂ (M = 267.11) calc .: molecular peak (MH) ^': 265/267/269 Found .: molecular peak (MH) " : 265/267/269

2.58b. 3 ', 4'-dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 102 mg (0.5 mmol) 2- (4- Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 134 mg (0.5 mmol) of 3 ', 4'-dichloro-biphenyl-4-carboxylic acid. Yield: 45 mg (19.8% of theory.) C 26 ^H 26 ^CI ° 2N2 (M = 453.42) Calc.: Molpeak (M + H) +: 453/455/457 Found: Molepeak (M + H) +: 453/455/457

Retention time HPLC: 6.45 min (Method A)

Example 2.59: 2 ', 4'-dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.59a. 2 ', 4'-dichloro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 5.23 g (26.0 mmol) of 4-bromo-benzoic acid and 10.0 g (52.0 mmol) of 2,4-dichlorophenylboronic acid, the reaction mixture being heated under reflux for 48 h. Yield: 1.5 g (21.6% of theory) of C ₃ H ₈ Cl ₂ O ₂ (M = 267.11) calc .: Mol peak (MH) ": 265/267/269 found: mol peak (MH) ^" : 265/267/269

2.59b. 2 ', 4'-dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 134 mg (0.5 mmol) of 2 ', 4'-dichloro-biphenyl-4-carboxylic acid.

Yield: 72 mg (31, 8% of theory)

C-26 26 ^CI 2 ^N 2 ° (M = 453.42) calc .: Mol peak (M + H) +: 453/455/457 found: Mol peak (M + H) +: 453/455/457

Retention time HPLC: 6.84 min (method A)

Example 2.60:

2'-fluoro-4'-chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.60a. 2'-fluoro-4'-chloro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 0.52 g (2.5 mmol) of 1-bromo-4-chloro-2-fluorobenzene and 0.5 g (3.0 mmol) of 4-carboxyphenylboronic acid.

Yield: 0.5 g (79.8% of theory)

C ₃ H ₈ CIF 0 ₂ (M = 250.66) calc .: Mol peak (MH) ^" : 249/251 found: Mol peak (MH)": 249/251

Retention time HPLC: 8.39 min (Method A)

2.60b. 2'-fluoro-4'-chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 125 mg (0.5 mmol) of 2'-fluoro-4'-chlorobiphenyl-4-carboxylic acid ,

Yield: 36 mg (16.5% of theory) of C-26 ^H 26CIFN ₂ O (M = 436.96) calc .: Mol peak (M + H) +: 437/439 found: mol peak (M + H) +: 437/439

Retention time HPLC: 6.32 min (method A)

Example 2.61:

3,4 "-dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.61a. 3,4'-dichloro-biphenyl-4-carboxylic acid Prepared analogously to Example 2.55a from 0.59 g (2.5 mmol) of 4-bromo-2-chloro-benzoic acid and 0.47 g (3.0 mmol) of 4-chlorophenylboronic acid. Yield: 0.55 g (82.4% of theory) C ₁₃ H ₈ Cl ₂ O (M = 267.11) calc .: Mol peak (MH) ^" : 265/267/269 found: mol peak (MH) ^" : 265/267/269

Retention time HPLC: 8.83 min (Method A)

2.61 b. 3,4'-dichloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidine 1-ylmethyl-phenyl) -ethylamine and 134 mg (0.5 mmol) of 3,4'-dichlorobiphenyl-4-carboxylic acid. Yield: 24 mg (10.6% of theory.) ^C 26 26 ^CI 2 ^N 2 ° (M = 453.42) calc .: molecular peak (M + H) +: 453/455/457 Found .: molecular peak (M + H) +: 453/455/457

Retention time HPLC: 6.41 min (Method A)

Example 2.62:

4'-Chloro-3-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.62a. 4'-chloro-3-fluoro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 0.55 g (2.5 mmol) of 4-bromo-2-fluorobenzoic acid and 0.47 g (3.0 mmol) of 4-chlorophenylboronic acid. Yield: 0.60 g (95.7% of theory) of C ₃ H ₈ CIFO ₂ (M = 250.66) calc .: Mol peak (MH) ": 249/251 F: Mol peak (MH) ^" : 249/251

Retention time HPLC: 8.22 min (Method A) 2.62b. 4'-Chloro-3-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethylphenyl) ethylamine and 125 mg (0.5 mmol) of 4'-chloro-3-fluorobiphenyl-4-carboxylic acid. Yield: 37 mg (16.9% of theory) C26 ^H 26 ^CIFN 2θ (M = 436.96) calc .: Mol peak (M + H) +: 437/439 found: Mol peak (M + H) +: 437/439 retention time HPLC: 6.45 min (method A)

Example 2.63:

4'-Chloro-2-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.63a. 4'-chloro-2-fluoro-biphenyl-4-carboxylic acid

Prepared analogously to Example 2.55a from 0.66 g (3.0 mmol) of 4-bromo-3-fluorobenzoic acid and 0.47 g (3.0 mmol) of 4-chlorophenylboronic acid. Yield: 0.60 g (79.8% of theory) C- ₃ H ₈ CIFO ₂ (M = 250.66) calc .: Mol peak (MH) ^" : 249/251 found: Mol peak (MH) ~: 249 / 251

Retention time HPLC: 8.50 min (method A)

2.63b. 4'-Chloro-2-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 163 mg (0.8 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 201 mg (0.8 mmol) of 4'-chloro-2-fluoro-biphenyl-4-carboxylic acid. Yield: 74 mg (21.2% of theory) C-26 ^H 26 ^CIFN 2θ ( ^M = 436.96) calc .: Mol peak (M + H) +: 437/439 found: Mol peak (M + H) +: 437/439

Retention time HPLC: 6.61 min (method A)

Example 2.64:

3-Nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.64a. 3-Nitro-biphenyl-4-carboxylic acid 150 mg (0.13 mmol) of tetrakis (triphenylphosphine) palladium are added to a solution of 1.0 g (4.07 mmol) of 4-bromo-2-nitrobenzoic acid in 20 ml of toluene and stirred for 10 min stirred at RT. Then, a solution of 0.5 g (4.10 mmol) phenyl boronic acid in 10 mL MeOH and one of 1.0 g Na ₂ C0 ₃ in 10 mL water. The reaction mixture is refluxed for 5 h and stirred at RT over the weekend. The solvents are removed in vacuo, the residue mixed with water, with conc. HCI acidified, extracted with EtOAc, the organic phase dried over Na ₂ S0 ₄ and then the solvent was removed. Yield: 0.87 g (87.5% of theory) R f value: 0.40 (silica gel, dichloromethane / ethanol 3: 1).

2.64b. 3-Nitro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 122 mg (0.5 mmol) of 3-nitro-biphenyl-4-carboxylic acid.

Yield: 100 mg (46.6% of theory) of C ₂ 6H ₂ 7N ₃ 0 ₃ (M = 429.52) calc .: Mol peak (M + H) +: 430 Found: Mol peak (M + H) + : 430 retention time HPLC: 5.83 min (method A) Example 2.65:

5- (4-Chloro-phenyl) -pyridine-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.65a. 5- (4-chloro-phenyl) -pyridine-2-carboxylic acid

Prepared analogously to Example 2.55a from 0.51 g (2.5 mmol) of 5-bromo-pyridine-2-carboxylic acid and 0.47 g (3.0 mmol) of 4-chlorophenylboronic acid. Yield: 0.23 g (39.4% of theory) of C ₂ H ₈ CINO 2 (M = 233.66) calc .: Mol peak (MH) ^" : 232/234 F: Mol peak (MH)": 232/234

Retention time HPLC: 5.89 min (Method A)

2.65b. 5- (4-Chloro-phenyl) -pyridine-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 102 mg (0.5 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 116 mg (0.5 mmol) of 5- (4-chlorophenyl) -pyric di-2-carboxylic acid. Yield: 7 mg (3.3% of theory)

C-25H26 ^CIN 3θ (M = 419.96) calc .: Mol peak (M + H) +: 420/422 Found: Mol peak (M + H) +: 420/422

Retention time HPLC: 6.40 min (Method A)

Example 2.66:

N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4-thiophen-3-yl-benzamide

2.66a. 4-Thiophen-3-yl-benzoesäureethylester Hergestellt analog Beispiel 2.46b aus 414 mg (1.5 mmol) 4-lod- benzoesäureethylester und 230 mg (1.8 mmol) Thiophen-3-boronsäure. Ausbeute: 348 mg (100 % d. Theorie) C-|₃Hι₂0₂S (M= 232,30) ber.: Molpeak (M+H)+: 233 gef.: Molpeak (M+H)+: 233

2.66a. Ethyl 4-thiophen-3-ylbenzoate Prepared analogously to Example 2.46b from 414 mg (1.5 mmol) of ethyl 4-iodobenzoate and 230 mg (1.8 mmol) of thiophene-3-boronic acid. Yield: 348 mg (100% of theory) C | ₃ Hι ₂ 0 ₂ S (M = 232.30) calc .: Mol peak (M + H) +: 233 found: Mol peak (M + H) +: 233

Retention time HPLC: 6.20 min (Method B)

2.66b. 4-thiophen-3-yl-benzoic acid

Prepared analogously to Example 2.7b from 280 mg (1.5 mmol) of ethyl 4-thiophen-3-yl-benzoate.

Yield: 146 mg (59.3% of theory)

C- | 1 H ₈ 0 ₂ S (M = 204.25) calc .: Mol peak (MH) ^" : 203 found: Mol peak (MH) ^" : 203

Retention time HPLC: 7.60 min (method A)

2.66c. N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4-thiophen-3-yl-benzamide Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1 -ylmethyl-phenyl) -ethylamine and 102 mg (0.5 mmol) of 4-thiophen-3-yl-benzoic acid.

Yield: 103 mg (53.0% of theory.) ^C 24 ^H 26 ^N 2θS (M = 390.55) calc .: molecular peak (M + H) +: 391 Found .: molecular peak (M + H) +: 391 Retention time HPLC: 6.10 min (method A)

Example 2.67:

N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4-thiophen-2-yl-benzamide

2.67a. 4-Thiophen-2-yl-benzoesäureethylester Hergestellt analog Beispiel 2.46b aus 414 mg (1.5 mmol) 4-lod- benzoesäureethylester und 230 mg (1.8 mmol) Thiophen-2-boronsäure. Ausbeute: 348 mg (100 % d. Theorie) Ci ₃H-| ₂0 S (M= 232,30) ber.: Molpeak (M+H)+: 233 gef.: Molpeak (M+H)+: 233

2.67a. Ethyl 4-thiophen-2-ylbenzoate Prepared analogously to Example 2.46b from 414 mg (1.5 mmol) of ethyl 4-iodobenzoate and 230 mg (1.8 mmol) of thiophene-2-boronic acid. Yield: 348 mg (100% of theory) of Ci ₃ H- | ₂ 0 S (M = 232.30) calc .: Mol peak (M + H) +: 233 found: Mol peak (M + H) +: 233

Retention time HPLC: 6.29 min (method B)

2.67b. 4-Thiophen-2-yl-benzoic acid Prepared analogously to Example 2.7b from 280 mg (1.5 mmol) of ethyl 4-thiophen-2-yl-benzoate.

Yield: 126 mg (51.2% of theory) Cϊ 1 H ₈ O ₂ S (M = 204.25) calc .: Mol peak (MH) ": 203 found: Mol peak (MH)": 203 retention time HPLC: 7.60 min (method A)

2.67c. N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4-thiophen-2-yl-benzamide Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1 -ylmethyl-phenyl) -ethylamine and 102 mg (0.5 mmol) of 4-thiophen-2-yl-benzoic acid.

Yield: 112 mg (57.5% of theory) C24H26 2OS (M = 390.55) calc .: Mol peak (M + H) +: 391 found: Mol peak (M + H) +: 391

Retention time HPLC: 6.05 min (Method A)

Example 2.68:

4- (5-chloro-thiophen-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.68a. 4-(5-Chlor-thiophen-2-yl)-benzoesäure

2.68a. 4- (5-chloro-thiophen-2-yl) benzoic acid

Prepared analogously to Example 2.55a from 300 mg (1.52 mmol) of 2-bromo-5-chlorothiophene and 277 mg (1.67 mmol) of 4-carboxyphenylboronic acid, using KHS0 ₄ solution to acidify the worked-up reaction mixture. Yield: 76 mg (21, 0% of theory) C ₁ H ₇ CI 0 S (M = 238.69) calc .: Mol peak (MH) ^" : 237/239 found: Mol peak (MH)": 237 / 239

Retention time HPLC: 8.75 min (method A)

2.68b. 4- (5-chloro-thiophen-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 61 mg (0.3 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 71 mg (0.3 mmol) of 4- (5-chloro-thiophen-2-yl) -benzoic acid. Yield: 29 mg (22.9% of theory)

C24H25CIN2OS (M = 425.0) calc .: Mol peak (M + H) +: 425/427 found: Mol peak (M + H) +: 425/427

Retention time HPLC: 6.65 min (Method A)

Example 2.69:

4-furan-2-yl-N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.69a, 4-furan-2-yl-benzoic acid Prepared analogously to Example 2.68a from 302 mg (1.5 mmol) of 4-bromo-benzoic acid and 201 mg (1.8 mmol) of furan-2-boronic acid. Yield: 166 mg (58.8% of theory) C _{| 1} H ₈ 0 ₃ (M = 188.19) calc .: Molpeak (MH) ": 187 found: Molpeak (MH)": 187 retention time HPLC: 6.82 min (Method A) 2.69b. 4-furan-2-yl-N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 102 mg (0.5 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 94 mg (0.5 mmol) of 4-furan-2-yl-benzoic acid.

Yield: 91 mg (48.4% of theory)

C24H26N2O2 (M = 374.49) Calcd .: Mol peak (M + H) +: 375 Found: Mol peak (M + H) +: 375

Retention time HPLC: 6.48 min (method A)

Example 2.70:

4- (5-methyl-pyridin-2-yl) -N- [2- (4-pyrrolidin-1-yimethyl-phenyl) -ethyl] -benzamide

2.70a. 4- (5-methyl-pyridin-2-yl) benzoic acid

Prepared analogously to Example 2.55a from 430 mg (2.50 mmol) of 2-bromo-5-methylpyridine and 498 mg (3.00 mmol) of 4-carboxyphenylboronic acid. Yield: 300 mg (56.3% of theory) C | ₃ Hι ι N0 ₂ (M = 213.24) calc .: Mol peak (M + H) +: 214 found: Mol peak (M + H) +: 214

Retention time HPLC: 4.55 min (Method A)

2.70b. 4- (5-Methylpyridin-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 102 mg (0.5 mmol) 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 107 mg (0.5 mmol) of 4- (5-methylpyridin-2-yl) -benzoic acid. Yield: 53 mg (26.5% of theory) of C ₂ 6H29N ₃ O (M = 399.54) Calc .: Mol peak (M + H) +: 400 Found: Mol peak (M + H) +: 400

Retention time HPLC: 3.98 min (Method A)

Example 2.71: 4- (6-Methylpyridin-3-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.71 a. 4- (6-methyl-pyridin-3-yl) benzoic acid

Prepared analogously to Example 2.55a from 430 mg (2.50 mmol) of 5-bromo-2-methylpyridine and 498 mg (3.00 mmol) of 4-carboxyphenylboronic acid. Yield: 300 mg (56.3% of theory) C ₁₃ H ₁ N0 ₂ (M = 213.24) calc .: Mol peak (M + H) +: 214 F: Mol peak (M + H) +: 214

Retention time HPLC: 2.66 min (method A)

2.71 b. 4- (6-Methyl-pyridin-3-yl) - N - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 102 mg (0.5 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 107 mg (0.5 mmol) of 4- (6-methylpyridin-3-yl) -benzoic acid ,

Yield: 48 mg (24.0% of theory) of C 26 H 29 N ₃ O (M = 399.54) calc .: Mol peak (M + H) +: 400 F: Mol peak (M + H) +: 400

Retention time HPLC: 3.06 min (method A)

Example 2.72:

4- (4-Chloro-phenyl) -thiophene-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.72a. 4- (4-chloro-phenyl) -thiophene-2-carbonsäuremethylester

420 mg (1.25 mmol) of methyl 4-bromo-thiophene-2-carboxylate are dissolved in 10 ml of dioxane and 5 ml of 2M-Na ₂ CO 3 solution. 196 mg (0.06 mmol) of 4-chloro-phenyl-boronic acid and 72 mg (0.06 mmol) of tetrakis (triphenylphosphine) palladium are added successively, the reaction is refluxed for 6 h and the mixture is stirred at RT for a further 60 h. After renewed heating, the hot reaction solution is filtered off with suction through a glass fiber filter, washed with dioxane, mixed with semisaturated NaHCO ₃ solution and extracted with EtOAc. The combined organic phases are dried over MgS0. After removal of the drying agent and solvent, the residue is purified by column chromatography on silica gel (petroleum ether / ethyl acetate 9: 1). Yield: 150 mg (47.3% of theory) of C12H9CIO2S (M = 252.72) calc .: Mol peak (M + H) +: 253/255 Found: Mol peak (M + H) +: 253/255

Retention time HPLC: 6.21 min (Method B)

2.72b. 4- (4-Chloro-phenyl) -thiophene-2-carboxylic acid To a solution of 150 mg of 4- (4-chloro-phenyl) -thiophene-2-carboxylic acid methyl ester in 10 mL EtOH is added 2 mL 1M NaOH solution and the Reaction solution stirred over the weekend at RT. The solvent is concentrated in vacuo, the residue is combined with 2 ml of 1 N hydrochloric acid and cooled to 0 ° C. The precipitated product is filtered off, washed with water and dried at 50 ° C. Yield: 140 mg (98.7% of theory) C ₁ - | H ₇ CI0 ₂ S (M = 238.69) calc .: Mol peak (M + H) +: 239/241 Found: Mol peak (M + H) +: 239/241

Retention time HPLC: 8.31 min (method A) 2.72c. 4- (4-Chloro-phenyl) -thiophene-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 144 mg (0.70 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 140 mg (0.59 mmol) of 4- (4-chlorophenyl) -thiophene-2-carboxylic acid.

Yield: 78 mg (31.3% of theory)

C ₂ 6H29N ₃ 0 (M = 425.00) calc.: Molpeak (M + H) +: 425/427 gef. : Molepeak (M + H) +: 425/427

Retention time HPLC: 3.90 min (Method A)

Example 2.73:

4- (5-acetyl-thiophen-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.73a. 4-iodo-N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2.04 g (10.0 mmol) 2- (4-

Pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 2.48 g (10.0 mmol) of 4-iodobenzoic acid.

Yield: 1.91 g (44.0% of theory) C20H23IN2O (M = 434.32) calc .: Mol peak (M + H) +: 435 F: Mol peak (M + H) +: 435

Retention time HPLC: 5.40 min (Method A)

2.73b. 4- (5-Acetylthiophene-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared analogously to Example 2.46b from 250 mg (0.58 mmol) 4-iodo-N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide and 118 mg (0.69 mmol) 5-acetyl-2- thiophenboronic acid, wherein the reaction mixture is heated under reflux for 15 h. Yield: 50 mg (20.2% of theory) of C ₂ H 6H 2 ^N 2 O 2 ^S (M = 432.59) Calc .: Molpeak (M + H) +: 433 Found: Molepeak (M + H) +: 433

Retention time HPLC: 3.91 min (Method B)

Example 2.74: 4- (5-Formylthiophene-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared analogously to Example 2.46b from 250 mg (0.58 mmol) of 4-iodo-N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide and 107 mg (0.69 mmol) of 5-formyl-2- thiophenboronic acid, wherein the reaction mixture is heated under reflux for 15 h. Yield: 22 mg (9.1% of theory) C-25H26N2O2S (M = 418.56) calc .: Mol peak (M + H) +: 419 Found: Mol peak (M + H) +: 419

Retention time HPLC: 3.82 min (Method B)

Example 2.75:

4'-Chloro-biphenyl-4-carboxylic acid [2- (4-aminomethyl-phenyl) -ethyl] -amide

2.75a. 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid ethyl ester To 9,31 g (40 mmol) of 4'-chlorobiphenyl-4-carboxylic acid are added dropwise 20 mL of thionyl chloride and 1 mL of DMF. The reaction mixture is heated to 60 ° C for 2 h. Subsequently, the excess thionyl chloride is removed under reduced pressure at 50 ° C. and the residue is taken up in 200 ml of CH ₂ Cl ₂ . This solution is added dropwise to 9.19 g (40 mmol) of ethyl 4- (2-aminoethyl) benzoate, used as hydrochloride, in 100 ml of 10% aqueous Na ₂ CO ₃ solution, and the reaction mixture is stirred at RT for a further hour touched. After addition of water and CH ₂ Cl ₂ , the organic phase separated, the aqueous phase extracted with CH ₂ Cl ₂ , the combined organic phases washed with half-saturated NaHC0 ₃ solution and water and dried over MgS0 ₄ . After removal of the drying agent, the solution is filtered through charcoal, concentrated in vacuo and the residue recrystallized from tert-butyl methyl ether. Yield: 11.93 g (73.1% of theory) C ₂₄ H ₂ 2CIN 0 ₃ (M = 407.90) calc .: Mol peak (M + H) +: 408 F: Mol peak (M + H) + : 408

Retention time HPLC: 9.8 min (Method A)

2.75b. 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid. To a solution of 11, 93 g (29.25 mmol) of 4- {2 - [(4'- Chloro-biphenyl-4-carbonyl) - amino] -ethyl} -benzoesäureethylester in 150 mL EtOH are added to 50 mL 2M NaOH solution and stirred for 2 h at RT. The reaction solution is brought to pH 6-7 with 1 N HCl solution, the precipitated product is filtered off and dried in a vacuum oven. Yield: 10.74 g (96.7% of theory) of C ₂ H ₂ O ₈ CIN 0 ₃ (M = 379.85) calc .: Mole peak (M + H) +: 380/382 F: mole peak (M + H ) +: 380/382 retention time HPLC: 8.0 min (method A)

2.75c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-hydroxymethyl-phenyl) -ethyl] -amide To a solution of 10.74 g (28.28 mmol) of 4- {2 - [(4'-chloro -biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid in 150 mL of dry THF 4.82 g (29.69 mmol) of CDI are added and the reaction mixture is heated to 50 ° C for 2 h. This

Solution is added to a suspension of 2.14 g (56.56 mmol) of NaBH ₄ in 5 mL of water and stirred vigorously for a further hour at RT. With the aid of 1 N HCl, the pH of the solution is brought to 6, this is mixed with EtOAc and filtered. The filtrate is washed with half-saturated NaHCO ₃ solution and with water and dried over MgSO ₄ . Since, after removal of the drying agent and solvent, the residue still contained unreacted 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid, the above reduction step was carried out again. The product obtained is dried at 40.degree. Yield: 9.3 g (89.9% of theory) of C22H20CINO2 (M = 365.86) calc .: Mole peak (M + H) +: 366/368 found: mole peak (M + H) +: 366 / 368

Retention time HPLC: 8.11 min (method A)

2.75d. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide To a solution of 7.9 g (21, 59 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [ 2- (4-hydroxymethyl-phenyl) -ethyl] -amide in 300 mL of CH ₂ Cl ₂ are added dropwise to 1, 22 ml of PBr ₃ . The reaction mixture is stirred overnight at RT. The resulting precipitate is filtered off with suction and the filtrate is concentrated. The residue is triturated with a little acetonitrile and CHCl ₂ , filtered off with suction, combined with the precipitate obtained first and dried in air. Yield: 8.6 g (92.9% of theory) of C ₂ 2H- | gBrCINO (M = 428.76) calc .: Mol peak (M + H) +: 428/430/432 Found: Mol peak (M + H ) +: 428/430/432

Rr value: 0.40 (silica gel, CH ₂ Cl ₂ ).

2.75e. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-aminomethyl-phenyl) -ethyl] -amide To a solution of 150 mg (0.35 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4 - Bromomethyl-phenyl) -ethyl] -amide in 10 mL acetonitrile are added 3 mL of a 0.5 M NH ₃ solution in dioxane and stirred for 3 days at RT. The reaction mixture is concentrated and the residue is purified by column chromatography (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1). Yield: 8 mg (6.3% of theory.) C22H21 CIN ₂ 0 (M = 364.88) calc .: molecular peak (M + H) +: 365/367 Found .: molecular peak (M + H) +: 365 / 367

Retention time HPLC: 5.97 min (method A)

Example 2.76: 4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(diisopropylamino) -methyl] -phenyl} -ethyl) -amide

To a suspension of 129 mg (0.3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 55 mg (0.4 mmol) of K ₂ C0 ₃ in 20 mL of acetonitrile 47 μL (0.33 mmol) of diisopropylamine are added and the

Reaction mixture stirred overnight at RT. It is diluted with CH ₂ Cl ₂ , filtered from insoluble inorganic salts and the filtrate is concentrated. The residue is triturated with acetonitrile, filtered off with suction and dried in air. Yield: 75 mg (55.7% of theory) of C2 ₈ H ₃₃ CIN 2 O (M = 449.04) Calculated: Mol peak (M + H) +: 449/451 Found: Molepeak (M + H) +: 449/451

Rr value: 0.35 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.77: 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3-oxo-piperazin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0.3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 33 mg (0.33 mmol) of piperazin-2-one.

Yield: 23 mg (17.1% of theory) of C 6 H 26 CIN ₃ O ₂ (M = 447.97) calc .: Mole peak (M + H) +: 448/450 Found: Molepeak (M + H) +: 448/450 R _f value: 0.10 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5). Example 2.78:

[(4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -methyl-amino] -acetic acid ethyl ester

Prepared analogously to Example 2.76 from 257 mg (0.6 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 193 mg K C0 ₃ and 101 mg (0.66 mmol) of methylamino ethyl acetate (used as hydrochloride). Yield: 152 mg (54.5% of theory.) C ₂ 7H29CIN ₂ 0 ₃ (M = 465.0) calc .: molecular peak (M + H) +: 465/467 Found .: molecular peak (M + H) + : 465/467

Rr value: 0.40 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.79: [(4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -methyl-amino] -acetic acid

To a solution of 80 mg (0.17 mmol) of ethyl [(4- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -methyl-amino] -acetic acid in 3 mL EtOH Add 0.3 mL of 1 M NaOH solution and heat at reflux for 1 h. The solvent is concentrated in vacuo and the residue treated with water and 0.3 mL 1 M HCl. The precipitate is filtered off with suction and dried at 40.degree. Yield: 76 mg (100% of theory) C 5 H 25 CIN ₂ O ₃ (M = 436.94) calc .: Mol peak (M + H) +: 437/439 found: Mol peak (M + H) +: 437 / 439 Retention time HPLC: 6.35 min (Method A)

Example 2.80:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (4-acetylpiperazin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0.3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 42 mg (0.33 mmol) of 1-piperazin-1-yl ethanone.

Yield: 60 mg (42.0% of theory) C ₂₈ H ₃ oCIN ₃ 0 ₂ (M = 476.02) calc .: Mole peak (M + H) +: 476/478 F: Mol peak (M + H ) +: 476/478

Rr value: 0.15 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.81:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-azabicyclo [2.2.1] hept-5-en-2-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0.3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 31 mg (0.33 mmol) of 2-azabicyclo [2.2 .1] hept-5-ene. Yield: 100 mg (. 75.2% of theory) C ₂₈ H27CIN ₂ 0 (M = 442.99) calc .: molecular peak (M + H) +: 443/445 Found .: molecular peak (M + H) +: 443/445 Rr value: 0.08 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.82:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1,3-dihydroisoindol-2-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0.3 mmol) 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 97 mg K ₂ CO ₃ and 51 mg (0.33 mmol) 2,3-dihydro-1H-isoindole (used as hydrochloride). Yield: 80 mg (57.1% of theory) of C ₃ oH ₂ 7CIN 0 (M = 467.02) calc.: Mole peak (M + H) +: 467/469. : Molepeak (M + H) +: 467/469

Rr value: 0.40 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.83:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (7-methyl-2,7-diaza-spiro [4.4] non-2-yl-methyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0.3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 46 mg (0.33 mmol) of 2-methyl-2,7 -diaza-spiro [4.4] nonane. Yield: 42 mg (28.7% of theory) C ₃ rjH ₃₄ CIN ₃ 0 (M = 488.08) calc .: Mole peak (M + H) +: 488/490 Found: Molepeak (M + H) ⁺ : 488/490 Rf value: 0.05 (silica gel, CH ₂ Cl ₂ / MeOH / NH 3 95: 5: 0.5).

Example 2.84:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3-diethylamino-azetidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 129 mg (0; 3 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 138 mg K ₂ C0 ₃ and 66 mg (0.33 mmol) azetidin-3-yl-diethyl-amine (used as bis-hydrochloride); the product is purified by column chromatography. Yield: 15 mg (10.5% of theory) C ₂ g H ₃₄ CIN ₃ O (M = 476.07) calc .: Mol peak (M + H) +: 476/478 found: Mol peak (M + H) +: 476/478 Rf value: 0.10 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.1).

Example 2.85:

(S) -1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidine-2-carboxylic acid ethyl ester

Prepared analogously to Example 2.76 from 257 mg (0.6 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 193 mg of K ₂ CO ₃ and 119 mg (0.66 mmol) (S) -pyrrolidine-2-carboxylic acid ethyl ester (used as the hydrochloride); the product is purified by column chromatography. Yield: 160 mg (54.3% of theory) of C ₂ H ₃ ιCIN ₂ O ₃ (M = 491, 04) calc .: Mole peak (M + H) +: 491/493 Found: Mole peak (M + H) + : 491/493

R _f value: 0.60 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.86:

(S) -1 - (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidine-2-carboxylic acid

Prepared analogously to Example 2.79 from 130 mg (0.27 mmol) of (S) -1- (4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} benzyl) -pyrrolidine-2 carboxylate. Yield: 120 mg (97.8% of theory) ^C 27 ^H 27 ^CIN 2 ° 3 ( ^M = 462.98) calc .: Mol peak (M + H) +: 463/465 found: Mol peak (M + H ) +: 463/465

HPLC retention time: 6 ^'20 min (Method A)

Example 2.87:

[1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester

Prepared analogously to Example 2.76 from 429 mg (1.0 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 205 mg (1.10 mmol) of pyrrolidin-3-yl-carbamic acid tert-butyl ester. Yield: 500 mg (93.6% of theory) C ₃₁ H ₃₆ CIN ₃ 0 ₃ (M = 534.10) calc .: Mole peak (M + H) +: 534/536 Found: Mol peak (M + H ) +: 534/536

Rr value: 0.33 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.88:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3-amino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

To a solution of 500 mg (0.94 mmol) of [1- (4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester in 15 mL CH ₂ Cl ₂ , 1 mL trifluoroacetic acid are added and the reaction is stirred overnight. This is then concentrated, the residue taken up in a little CH _≥ CI ₂ and mixed with half-saturated NaHC0 ₃ solution. The precipitated product is filtered off with suction, triturated with acetonitrile and dried at 40.degree.

Yield: 240 mg (59.1% of theory) ^C 26 28 ^CIN 3 ° ( ^M = 433.99) calc .: Mol peak (M + H) +: 434/436 Found: Mol peak (M + H) + : 434/436

Rr value: 0.22 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

Example 2.89:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3-dimethylamino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

Zu einer Lösung von 60 mg (0.14 mmol) 4'-Chlor-biphenyl-4-carbonsäure{2-[4-(3- amino-pyrrolidin-1-ylmethyl)-phenyl]-ethyl}-amid in 5 mL Acetonitril werden 0.12 mL 37% wässrige Formaldehyd-Lösung, 28 mg (0.45 mmol) NaBH₃CN und ein Tropfen Eisessig zugegeben. Das Reaktionsgemisch wird über Nacht bei RT gerührt und dann mit verdünnter NaOH-Lösung und EtOAc versetzt. Die Phasen werden getrennt, die organische über MgS0₄ getrocknet und anschliessend vom Trocken- und Lösungsmittel befreit. Der Rückstand wird mittels Säulenchromatographie gereinigt. Ausbeute: 10 mg (15,7 % d. Theorie) C₂₈H₃2CIN₃0 (M= 462,04) ber.: Molpeak (M+H)+: 462/464 gef.: Molpeak (M+H)+: 462/464

To a solution of 60 mg (0.14 mmol) 4'-chlorobiphenyl-4-carboxylic acid {2- [4- (3-aminopyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide in 5 mL acetonitrile Add 0.12 mL of 37% aqueous formaldehyde solution, 28 mg (0.45 mmol) of NaBH ₃ CN, and one drop of glacial acetic acid. The reaction mixture is stirred overnight at RT and then treated with dilute NaOH solution and EtOAc. The phases are separated, the organic dried over MgS0 ₄ and then freed from the dry and solvent. The residue is purified by column chromatography. Yield: 10 mg (15.7% theory d.) C ₂₈ H ₃ 2CIN ₃ 0 (M = 462.04) calc .: molecular peak (M + H) +: 462/464 Found .: molecular peak (M + H) +: 462/464

Retention time HPLC: 5.16 min (method A)

Example 2.90:

[1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-2-yl-methyl] -carbamic acid tert-butyl ester

Prepared analogously to Example 2.76 from 230 mg (0.54 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide and 116 mg (1.10 mmol) of pyrrolidin-2-ylmethyl-carbamic acid tert-butyl ester. Yield: 230 mg (78.3% of theory) C ₃₂ H ₃₈ CIN ₃ 0 ₃ (M = 548.13) calc .: Mole peak (M + H) +: 548/550 F: Mol peak (M + H ) +: 548/550

Rr value: 0.35 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

Example 2.91: 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-aminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.88 from 230 mg (0.42 mmol) of [1- (4- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-2-ylmethyl] - carbamic acid tert-butyl ester

Yield: 188 mg (100% of theory) C ₂ 7H ₃₀ CIN ₃ O (M = 448.01) calc .: Mole peak (M + H) +: 448/450 Found: Molepeak (M + H) +: 448/450

Rr value: 0.35 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

Example 2.92:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-dimethylaminomethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.89 from 40 mg (0.09 mmol) of 4'-chlorobiphenyl-4-carboxylic acid {2- [4- (2-aminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide, 0.08 mL 37 % aqueous formaldehyde solution and 19 mg (0.30 mmol) NaBH ₃ CN. Yield: 10 mg (23.6% of theory.) C29H ₃₄ CIN ₃ 0 (M = 476.07) calc .: molecular peak (M + H) +: 476/478 Found .: molecular peak (M + H) +: 476/478 Rr value: 0.12 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

Example 2.93:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methyl-2,6-diaza-spiro [3,4] oct-6-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.76 from 250 mg (0.58 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 97 mg of K ₂ CO ₃ and 81 mg (0.64 mmol) 2-methyl-2,6-diaza-spiro [3.4] octane; the product is purified by HPLC.

Yield: 20 mg (7.2% of theory) C ₂ gH ₃₂ CIN ₃ O (M = 474.05) calc .: Mol peak (M + H) +: 474/476 found: Mol peak (M + H) +: 474/476 Rf value: 0.20 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

Example 2.94:

3 - [(4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -ethyl-amino] -propionic acid

A suspension of 257 mg (0.6 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-bromomethyl-phenyl) -ethyl] -amide, 166 mg (1.2 mmol) of K ₂ CO ₃ and 138 mg of 3 Ethylamino-propionic acid (0.9 mmol, used as hydrochloride) in 20 mL acetonitrile is stirred for 3 days at RT. Add 5 mL DMF and warm to warm 50 ° C for 3 h. The reaction mixture is filtered, the filtrate is concentrated and the residue is purified by HPLC. Yield: 50 mg (17.9% of theory) C27H29CIN ₂ 0 ₃ (M = 465.0) calc .: Mol peak (M + H) +: 465/467 found: Mol peak (M + H) +: 465 / 467

Retention time HPLC: 5.85 min (Method A)

Example 2.95:

(S) -1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidine-2-carboxylic acid, methyl ester

2.95a. Ethyl 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoate Prepared according to general procedure I from 10.0 g (42.98 mmol) of 4'-chlorobiphenyl-4-carboxylic acid and 9.87 g (42.98 mmol) of ethyl 4- (2-aminoethyl) benzoate. Yield: 10.64 g (60.7% of theory) of C ₂₄ H 2CINO ₃ (M = 407.90) calc .: Mole peak (M + H) +: 408/410 found: mol peak (M + H) +: 408/410 R _f value: 0.87 (silica gel, CH ₂ Cl ₂ / MeOH 95: 5).

2.95b. 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid To a solution of 10.64 g (26.08 mmol) of 4- {2 - [(4'-chlorobiphenyl) 4-carbonyl) - amino] -ethyl} -benzoesäureethylester in 100 mL of EtOH 14 mL 2 M NaOH solution and the reaction mixture heated to 60 ° C overnight. Then another 30 mL NaOH solution is added and this temperature is maintained for a further 3 hours. The reaction mixture is brought to pH 6-7 with 1 M HCl solution, the precipitated product is filtered off and dried in vacuo. Yield: 7.65 g (77.2% of theory) of C ₂ 2H- | ₈ CIN0 ₃ (M = 379.85) calc .: Mol peak (M + H) +: 380/382 found: Mol peak (M + H) +: 380/382

Retention time HPLC: 8.1 min (method A)

2.95c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-hydroxymethyl-phenyl) -ethyl] -amide To a solution of 7.2 g (18.97 mmol) of 4- {2 - [(4'-chloro-biphenyl-4 -carbonyl) -amino] -ethyl} -benzoic acid in 150 mL of dry THF 3.24 g (20 mmol) of CDI are added and the reaction mixture heated to 50 ° C for 2 h. This solution is added to a suspension of 1.44 g (38 mmol) of NaBH ₄ in 5 ml of water and stirred for an additional hour. The reaction mixture is brought to pH 6-7 with 1 M HCl solution and extracted exhaustively with EtOAc. The organic phase is washed with NaHC0 ₃ solution and with water and dried over MgS0. After removal of the drying agent and solvent, the residue is purified by chromatography (silica gel, _CH ₂ Cl ₂ / MeOH 9: 1). Since there is still educt in the product, the procedure described above is repeated with 50% of the reagents used. Yield: 2.85 g (41.0% of theory) C22H20CINO2 (M = 365.86) calc .: Mol peak (M + H) +: 366/368 found: Mol peak (M + H) +: 366 / 368

Retention time HPLC: 8.0 min (Method A)

2.95d. Methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester To a solution of 1.0 g (2.73 mmol) 4'-chlorobiphenyl-4-carboxylic acid [2 - (4-hydroxymethyl-phenyl) -ethyl] -amide in 100 mL of dry THF are added 1.25 mL (9 mmol) of triethylamine and cooled to -20 ° C. Then 0.64 mL (8.2 mmol) of methanesulfonyl chloride are added dropwise and the mixture is stirred at this temperature for a further 2 h. Add 5% NaHCO ₃ solution and exhaustively with EtOAc. The organic phase is dried over Na ₂ S0 ₄ , the drying and solvent removed and the residue dried at 30 ° C in vacuo. Yield: 1.21 g (99.7% of theory) C ₂₃ H ₂ 2CINO ₄ S (M = 443.95) calc .: Mol peak (M + H) +: 444/446 Found: Mol peak (M + H) +: 444/446

Retention time HPLC: 8.8 min (method A)

2.95e. (S) -1 - (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidine-2-carboxylic acid, methyl ester

Under N ₂ atmosphere, a solution of 50 mg (0.3 mmol) of (2S) -pyrrolidine-2-carboxylic acid methyl ester (used as hydrochloride) and 0.7 mL (0.5 mmol) of triethylamine in 4 mL of DMF is stirred for 20 min at RT. Then 111 mg (0.25 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} - benzyl ester are added and heated to 60 ° C for 2 h. The reaction mixture is concentrated in vacuo and the residue purified by HPLC. Yield: 4 mg (3.4% of theory.) C ₂₈ H29CIN ₂ 0 ₃ (M = 477.01) calc .: molecular peak (M + H) +: 477/479 Found .: molecular peak (M + H) + : 477/479

Retention time HPLC: 6.51 min (Method A)

Example 2.96:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpiperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 35 μL (0.3 mmol) of 2-methypiperidine without use of triethylamine. Yield: 7 mg (6.3% of theory) C ₂₈ H ₃ ιCIN ₂ O (M = 447.03) calc .: Mol peak (M + H) +: 447/449 found: mol peak (M + H) +: 447/449

Retention time HPLC: 6.4 min (method A) Example 2.97:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 32 μL (0.3 mmol) of 2-methyl- pyrrolidine without the use of triethylamine. Yield: 2 mg (1.8% of theory) C27H29CIN2O (M = 433.0) calc .: Mol peak (M + H) +: 433/435 Found: Mol peak (M + H) +: 433/435

Retention time HPLC: 6.3 min (Method A)

Example 2.98:

4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(cyclopropylmethyl-amino) -methyl] -phenyl} -ethyl) -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzylester and 26 .mu.L (0.3 mmol) cyclopropylmethylamine without using triethylamine. Yield: 4 mg (3.8% of theory) C26H27CIN2O (M = 418.97) calc .: Mol peak (M + H) +: 418/420 Found: Mol peak (M + H) +: 418/420

Retention time HPLC: 6.4 min (method A) Example 2.99:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3,4-dihydro-1H-isoquinolin-2-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 40 mg (0.3 mmol) 1, 2, 3,4-tetrahydroisoquinoline without the use of triethylamine. Yield: 21 mg (17.5% of theory.) C ₂ 6H ₂ 7CIN ₂ 0 (M = 481, 04) calc .: molecular peak (M + H) +: 481/483 Found .: molecular peak (M + H) +: 481/483

Retention time HPLC: 6.8 min (Method A)

Example 2.100:

4'-Chloro-biphenyl-4-carboxylic acid [2- (4 - {[(2-hydroxy-ethyl) -methyl-amino] -methyl} -phenyl) -ethyl] -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 24 μL (0.3 mmol) of 2-methylamino ethanol without the use of triethylamine. Yield: 13 mg (12.3% of theory) C25H27CIN2O2 (M = 422.96) calc .: Mol peak (M + H) +: 423/425 found: Mol peak (M + H) +: 423/425 retention time HPLC: 5.8 min (Method A) Example 2.101:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2,6-dimethyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide

Hergestellt analog Beispiel 2.95e aus 111 mg (0.42 mmol) Methansulfonsäure 4- {2-[(4'-chlor-biphenyl-4-carbonyl)-amino]-ethyl}-benzylester und 41 μL (0.3 mmol) 2,6-Dimethylpiperidin ohne Verwendung von Triethylamin. Ausbeute: 8 mg (6,9 % d. Theorie) C gH₃₃CIN₂0 (M= 461 ,05) ber.: Molpeak (M+H)+: 461/463 gef.: Molpeak (M+H)+: 461/463

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 41 μL (0.3 mmol) 2,6- Dimethylpiperidine without use of triethylamine. Yield: 8 mg (6.9% of theory) C g H ₃₃ CIN ₂ O (M = 461, 05) calc .: Mole peak (M + H) +: 461/463 Found: Mol peak (M + H) + : 461/463

Retention time HPLC: 6.6 min (method A)

Example 2.102:

4'-Chloro-biphenyl-4-carboxylic acid [2- (4-azetidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 2.95e from 111 mg (0.42 mmol) of methanesulfonic acid 4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzylester and 20 μL (0.3 mmol) of azetidine without using triethylamine. Yield: 3 mg (3.0% of theory) C 25 H 25 CIN 2 O (M = 404.94) calc .: Mol peak (M + H) +: 405/407 F: Mol peak (M + H) +: 405/407

Retention time HPLC: 5.9 min (Method A)

Example 2.103: 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared analogously to Example 2.95e from 50 mg (0.11 mmol) of methanesulfonic acid 4- {2- [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl ester and 11 μL (0.14 mmol) 2,5- Dihydro-1H-pyrrole without the use of triethylamine. Yield: 18 mg (38.2% of theory) C26H25CIN2O (M = 416.95) calc .: Mol peak (M + H) +: 417/419 Found: Mol peak (M + H) +: 417/419

Retention time HPLC: 6.2 min (method A)

Example 2.104:

4'-Bromo-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-yl-methyl) -phenyl] -ethyl} -amide

2.104a. 4'-bromo-biphenyl-4-carboxylic acid ethyl ester

Prepared analogously to Example 2.46b from 1.22 mL (7.47 mmol) of ethyl 4-bromo-benzoate and 1.8 g (8.96 mmol) of 4-bromophenylboronic acid, while refluxing for 72 h. The product is crystallized from acetonitrile. Yield: 293 mg (12.8% of theory) C | ₅ H ₁₃ BrO 2 (M = 305.17) calc .: Mol peak (M + H) +: 304/306 Found: Mol peak (M + H) +: 304/306

Rr value: 0.9 (silica gel, petroleum ether / EtOAc 6: 4).

2.104b.4'-Bromo-biphenyl-4-carboxylic acid To a solution of 270 mg (0.89 mmol) of ethyl 4'-bromo-biphenyl-4-carboxylate in 10 mL EtOH is added 1.24 mL 2M NaOH solution and the reaction mixture stirred for 2 h at RT. The pH is adjusted to 6-7 with 1 M HCl, the precipitated product is filtered off and dried. Yield: 205 mg (83.6% of theory) of C ₁₃ H ₉ BrO ₂ (M = 277.12) calc .: Mol peak (MH) ^" : 275/277 found: Mol peak (MH)": 275/277

Retention time HPLC: 8.5 min (Method A)

2.104c. [4- (2-Amino-ethyl) -phenyl] -methanol

To 5.8 g (39.41 mmol) of (4-hydroxymethyl-phenyl) -acetonitrile (see Example 1.1e.) In 116 mL of methanolic NH ₃ solution, 580 mg of Raney nickel are added and the reaction mixture is hydrogenated at 50 psi H ₂ . After completion of the reaction, the catalyst is filtered off, the solvent is removed and the residue is purified by chromatography (silica gel, EtOAc / MeOH / NH ₃ 7: 3: 0.3). Yield: 3.9 g (65.4% of theory) CgH ₁₃ NO (M. = 151, 21).: Molepeak (M + H) +: 152. : Molepeak (M + H) +: 152

R _f value: 0.18 (silica gel, EtOAc / MeOH / NH ₃ 8: 2: 0.2).

2.104d. [2- (4-hydroxymethyl-phenyl) -ethyl] -carbamic acid tert-butyl ester To a solution of 2.5 g (16.53 mmol) of [4- (2-amino-ethyl) -phenyl] -methanol in 50 mL of CH ₂ Cl ₂ , 17.36 mL of a 1 M BOC anhydride in CH ₂ Cl _{2 are} added at RT and the reaction mixture is stirred at RT overnight. 100 ml of KHSO ₄ solution are added, the organic phase is separated off, washed with dilute NaHCO ₃ solution and water and dried over MgSO ₄ . After removal of the drying agent and solvent, the desired product is obtained. Yield: 4.06 g (97.7% of theory) of C-] ₄ H ₂ ι N0 ₃ (M = 251, 33) calc .: Mol peak (M + H) +: 252 found: Mol peak (M + H) +: 252

Retention time HPLC: 6.4 min (method A)

2.104e. [2- (4-chloromethyl-phenyl) -ethyl] -carbamic acid tert-butyl ester

To a solution of 2.6 g (10.35 mmol) of [2- (4-hydroxymethyl-phenyl) -ethyl] -carbamic acid tert-butyl ester in 50 mL of CH ₂ Cl ₂ is added 1 mL of pyridine, to 0 ° C cooled and 1.03 mL (12.41 mmol) of thionyl chloride added. It is kept for 1 h at 0 ° C and then allowed to warm to rt. The reaction mixture is washed with water, dilute KHS0 ₄ solution and again with water, dried with MgS0 and filtered through charcoal. After removal of the solvent, the product is obtained as an oil, which is reacted without further purification. Yield: 1.8 g (64.5% of theory) C ₁₄ H ₂ oCINO ₂ (M = 269.77) calc .: Mole peak (MH) ^" : 268/270 F: Mol peak (MH)": 268/270

Rr value: 0.62 (silica gel, petroleum ether / EtOAc 7: 3).

2.104f. {2- [4- (2,5-Dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -carbamic acid tert-butyl ester

To a solution of 1.4 g (5.19 mmol) of [2- (4-chloromethyl-phenyl) -ethyl] -carbamic acid tert-butyl ester in 50 ml of acetonitrile are added 2.37 g (17.13 mmol) of K ₂ CO ₃ and 0.8 ml (10.38 mmol ) Was added 2,5-dihydro-1H-pyrrole and stirred at RT overnight. The reaction mixture is diluted with CH ₂ Cl ₂ , washed with water and dried over MgS0 ₄ . After removing the dry and

Solvent gives the desired product.

Yield: 1.46 g (93.0% of theory) of C1 ₈ H ₂ 6N ₂ O ₂ (M = 302.42) calc .: Mole peak (M + H) +: 303 F: Mol peak (M + H) +: 303

Rr value: 0.15 (silica gel, petroleum ether / EtOAc 7: 3).

2.104g. 2- [4- (2,5-Dihydro-pyrrol-1-ylmethyl) -phenyl] -ethylamine To a solution of 1.21 g (4 mmol) of {2- [4- (2,5-dihydro-pyrrol-1-yl) ylmethyl) -phenyl] - ethyl} -carbamic acid tert-butyl ester in 50 mL CH ₂ Cl ₂ are added 5 mL trifluoroacetic acid and stirred at RT for 2 h. The reaction mixture is concentrated in vacuo, the residue is combined with water and CH ₂ Cl ₂ and made alkaline with K ₂ C0 solution. The organic phase is separated, washed with water and dried over MgS0 ₄ . After removal of the drying agent and solvent, the desired product is obtained. Yield: 0.35 g (43.3% of theory) of C ₃ H ₁₈ N ₂ (M: = 202.30) Calc .: Mol peak (M + H) +: 203 Found: Mol peak (M + H) +: 203

Rr value: 0.05 (silica gel, EtOAc / MeOH / NH ₃ 9: 1: 0.1).

2.104h. 4'-Bromo-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

Prepared according to general procedure I from 139 mg (0.50 mmol) 4'-

Bromo-biphenyl-4-carboxylic acid and 101 mg (0.50 mmol) of 2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl-ethylamine.

Yield: 21 mg (9.1% of theory) C ₂ 6H 25 BrN 0 (M = 461, 41) Calcd .: Mol peak (M + H) +: 461/463 Found: Mol peak (M + H) +: 461 / 463

Retention time HPLC: 6.46 min (Method A)

Example 2.105: 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethyl} -amide

2.105a. (4-pyridin-2-yl-phenyl) -acetonitrile

Prepared analogously to Example 2.46b from 0.52 mL (5.40 mmol) of 2-bromo-pyridine and 1.0 g (5.96 mmol) of 4-Cyanmethyiphenyl-boronic acid. After removal of the drying and solvent, the residue is triturated with diisopropyl ether and dried in air.

Yield: 0.76 g (72.5% of theory) C | ₃ H | | ₀ N2 (M = 194.24) calc.: Molpeak (M + H) +: 195. : Molepeak (M + H) +: 195 Retention time HPLC: 3.56 min (Method B)

ber.: Molpeak (M)+: 223 gef.: Molpeak (M)+: 2232.105b. 2- (4-cyanomethyl-phenyl) -1-ethyl-pyridinium iodide To a solution of 760 mg (3.91 mmol) (4-pyridin-2-yl-phenyl) -acetonitrile in 5 mL DMF are added 0.38 mL (4.7 mmol) of ethyl iodide and stirred overnight at RT. To complete the reaction, the solution is treated for 20 minutes at 120 ° C in the microwave. The solvent is concentrated under reduced pressure, the residue is combined with water and extracted with EtOAc. The aqueous phase is concentrated by evaporation, the residue is triturated with THF and the suspension is cooled to 0 ° C. The product is filtered off with suction and dried at 50.degree. Yield: 800 mg (58.4% of theory)

Calc .: Molpeak (M) +: 223 Found: Molpeak (M) +: 223

Retention time HPLC: 1.76 min (Method A)

2.105c. 2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethylamine

To a solution of 800 mg (2.28 mmol) 2- (4-cyanomethyl-phenyl) -1-ethyl-pyridinium iodide in 10 mL methanolic NH ₃ is added 100 mg Raney nickel and the reaction mixture at 20 psi and RT 24 h in Autoclaved hydrogenated. The catalyst is filtered off with suction, the reaction solution is admixed with 100 mg of PtO ₂ and again hydrogenated at RT and for 20 psi for 30 h. After removal of the catalyst, the product is obtained (as hydroiodide), which is reacted further without purification.

Yield: 700 mg (85.1% of theory.) C- | IN 5H ₂₄ (M = 360.28) calc .: molecular peak (M) +: 233 Found .: molecular peak (M) +: 233

Retention time HPLC: 0.93 min (isocratic water: acetonitrile: formic acid 95: 5: 0.01 over 8 min).

2.105d. 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethyl} -amide

Prepared according to general procedure I from 480 mg (1.33 mmol) of 2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethylamine (used as hydroiodide) and 310 mg (1.33 mmol) of 4'-chlorine biphenyl-4-carboxylic acid. Yield: 20 mg (3.4% of theory) C28 31 ^CIN 2θ (= 447.03) Calc .: Molpeak (M + H) +: 447/449 Found: Molpeak (M + H) +: 447/449

Retention time HPLC: 6.68 min (method A)

Example 2.106: 4'-Chloro-biphenyl-4-carboxylic acid [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -amide

2.106a. (E) -3- (1-oxo-indan-5-yl) -acrylic acid ethyl ester

To a solution of 4.64 g (21.99 mmol) of 5-bromo-indan-1-one in 110 mL of triethylamine under N2 5.96 mL (55 mmol) of ethyl acrylate, 275 mg

(1.21 mmol) Pd (OAc) ₂ and 704 mg (2.31 mmol) of tri-o-tolyphospin and the reaction mixture heated to 100 ° C for 4 h. The solvent is distilled off, the residue is combined with 150 mL EtOAc and 100 mL ice-water, treated with conc. HCI acidified, the organic phase washed with 100 mL of water and dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography (silica gel, hexane / EtOAc 9: 1 after

8: 2)

Yield: 4.0 g (79.0% of theory)

Melting point: 100-102 ° C

2.106b. (E) -3- (1-oxo-indan-5-yl) -acrylic acid

To a solution of 4.0 g (17.0 mmol) ethyl (E) -3- (1-oxo-indan-5-yl) -acrylate in 50 mL MeOH 10 mL 2 N NaOH are added and the

Reaction mixture heated for 30 min under reflux. Then it is mixed with 11 mL of 2N HCl solution, MeOH distilled off, the crystals are filtered off with suction and dried.

Yield: 3.0 g (87.3% of theory)

Melting point: 240-244 ° C 2.106c. 3- (1-oxo-indan-5-yl) propionic acid

To a solution of 1.6 g (7.91 mmol) of (E) -3- (1-oxo-indan-5-yl) -acrylic acid in 50 mL MeOH 150 mg 10% Pd / C are added and the reaction mixture at RT and 3 bar H2 shaken to theoretical uptake of H ₂ in the Parr autoclave. It is mixed with 10 mL of 1 N NaOH and the solvent is removed. The residue is acidified with dilute HCl, extracted exhaustively with EtOAc and the organic phase dried over MgS0. After removal of the drying agent and solvent, the residue is triturated with tert-butyl methyl ether, the precipitate is filtered off with suction and dried. Yield: 500 mg (31.0% of theory) C | ₂ H 2θ ₃ (M = 204.23) calc .: Mol peak (MH) ": 203 F: Mol peak (MH)": 203 Rr value: 0.45 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1).

2.106d. [2- (1-oxo-indan-5-yl) -ethyl] -carbamic acid tert-butyl ester

Under an argon atmosphere, 1.6 g (7.83 mmol) of 3- (1-oxo-indan-5-yl) - propionic acid in 25 ml of tert. Butanol and 2.5 mL of triethylamine presented. To this solution, 2.22 mL (10.0 mmol) of diphenyl azido-phosphoric acid are added and heated to 80 ° C for 3 h. The reaction mixture is concentrated in vacuo and the residue is purified by chromatography on silica gel. Yield: 750 mg (34.8% of theory) C ₁₆ H 10 N ₃ (M = 275.35) calc .: Mol peak (M) +: 275 F: Mol peak (M) +: 275

Rr value: 0.65 (silica gel, CH ₂ Cl ₂ / MeOH 95: 5).

2.106e. [2- (1-Hydroxy-indan-5-yl) -ethyl] -carbamic acid tert -butyl ester To a solution of 700 mg (2.54 mmol) of [2- (1-oxo-indan-5-yl) -ethyl] - Carbamic acid tert-butyl ester in 70 mL MeOH 700 mg (18.5 mmol) NaBH _{4 are} added in portions and stirred at RT overnight. The reaction solution is carefully mixed with 10% KHSO solution, diluted with water and extracted exhaustively with tert-butylmethyl ether. The organic phase is washed with water and dried over MgS0 ₄ . After removal of the dry and solvent, the residue is purified by chromatography on silica gel. Yield: 350 mg (49.7% of theory) C ₁₆ H ₂₃ N0 ₃ (M = 277.37) calc .: Mole peak (M) +: 277 F: Mol peak (M) +: 277

Rr value: 0.30 (silica gel, petroleum ether / EtOAc 6: 4).

2.106f. [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -carbamic acid tert-butyl ester

To a cooled to 0 ° C solution of 350 mg (1.26 mmol) of [2- (1-hydroxy-indan-5-yl) -ethyl] -carbaminsäure tert-butyl ester in 7.5 mL CH ₂ Cl ₂ are 109 μL (1.5 mmol) thionyl chloride (dissolved in a little CH ₂ Cl ₂ ) is slowly added dropwise. Stirring is continued for 30 min at 10 ° C, added to the reaction solution with ice-cold NaHCOs- solution, the organic phase is separated off, washed with cold water and dried over MgS0. ₄ After removal of the dry by means of the filtrate is cooled to 0 ° C, 417 .mu.L (5.0 mmol) of pyrrolidine are added dropwise and the Reaktionsgemsich stirred overnight at RT. The reaction mixture is concentrated and the residue is purified by chromatography on silica gel. Yield: 120 mg (28.8% of theory.) C20 ^H 30 ^N 2θ2 (M = 330.47) calc .: molecular peak (M + H) +: 331 Found .: molecular peak (M + H) +: 331

Retention time HPLC: 5.6 min (method A)

2.106g. 2- (1-pyrrolidin-1-yl-indan-5-yl) ethylamine

To a solution of 100 mg (0.3 mmol) of [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -carbamic acid tert-butyl ester in 10 mL of CH ₂ Cl ₂ with gentle cooling 100 μL Added trifluoroacetic acid and stirred for 1 h at RT. To complete the reaction, another 500 μL trifluoroacetic acid is added with cooling and stirred for 2 h at RT. The reaction mixture is concentrated in vacuo and the product is further reacted (as bis-trifluoroacetate) without purification. Yield: 100 mg (72.7% of theory) ^C 19 24 F ₆ N ₂ O ₄ (M = 458.51) calc .: Mole peak (M + H) +: 231 Found: Molepeak (M + H) +: 231

Rr value: 0.3 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1). 2.106h. 4'-Chloro-biphenyl-4-carboxylic acid [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -amide

Prepared according to general procedure I from 100 mg (0.29 mmol) of 2- (1-pyrrolidin-1-yl-indan-5-yl) -ethylamine (used as bis-trifluoroacetate) and 70 mg (0.3 mmol) of 4'-chlorine biphenyl-4-carboxylic acid. Yield: 40 mg (30.0% of theory) of C ₂₈ H ₂ gCIN ₂ O (M = 445.01) calc .: Mole peak (M + H) +: 445/447 F: Mol peak (M + H) +: 445/447 retention time HPLC: 6.65 min (method A)

Example 2.107:

4'-Chloro-biphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.107a. 2-bromo-4-cyanomethyl-benzoic acid methyl ester

To a solution of 24.51 g (0.5 mol) of NaCN in 40 mL of water is added a solution of 98.55 g (0.32 mol) of 2-bromo-4-bromomethyl-benzoic acid methyl ester in 60 mL of EtOH and the reaction mixture heated under reflux for 5 h. It is mixed with 1 L of tert-butyl methyl ether and 500 mL water, the organic phase is separated, it is washed several times with water and dried over MgS0. ₄ After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (petroleum ether / EtOAc 8: 2). Yield: 15.0 g (16.6% of theory) C ₀ H ₈ BrNO ₂ (M = 254.09) calc .: Mol peak (MH) ": 252/254 F: Mol peak (MH)": 252/254 2.107b. 2-bromo-4-cyanomethyl-benzoic acid

To a solution of 7.9 g (31.0 mmol) of methyl 2-bromo-4-cyanomethylbenzoate in 100 ml of EtOH, 35 ml of 1M NaOH solution are added, the reaction mixture is refluxed for 1 h and then stirred at RT overnight. It is mixed with ice-water and acidified with dilute KHS0 ₄ solution. The precipitate is filtered off with suction, washed with water and dried at 50.degree. Yield: 6.2 g (83.3% of theory) CgH ₆ BrN 0 (M = 240.06) calc .: Mol peak (MH) ": 238/240 F: Mol peak (MH)": 238/240

Retention time HPLC: 3.99 min (method B)

2.107c. (3-Bromo-4-hydroxymethyl-phenyl) -acetonitrile

To a solution of 2.4 g (10 mmol) 2-bromo-4-cyanomethyl-benzoic acid in 50 mL THF are added 1.78 g (11 mmol) of CDI and until the end of the

Gas evolution heated in a water bath. Subsequently, this becomes one

Solution of 0.76 g (20 mmol) of NaBH ₄ in 50 mL of water was added, with the

Temperature should not exceed 30 ° C. Stirring is continued for 2 h at RT, the reaction mixture is acidified carefully with dilute KHS0 ₄ solution and extracted exhaustively with tert-butyl methyl ether, the organic phase washed with water and dried over MgS0 ₄ washes. It is filtered through activated charcoal and removed

Solvent in a vacuum.

Yield: 2.2 g (97.3% of theory)

C ₉ H ₈ BrN 0 (M = 226.07) calc .: Mol peak (MH) ": 224/226 found: Mol peak (MH)": 224/226

Rr value: 0.6 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1).

2.107d. (3-Bromo-4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile To a solution of 1.9 g (8.4 mmol) (3-bromo-4-hydroxymethyl-phenyl) -acetonitrile in 50 mL CH ₂ Cl ₂ 1.25 mL (9 mmol) of triethylamine, cooled to 0 ° C and added dropwise a solution of 0.66 mL (8.5 mmol) of methanesulfonyl chloride in 10 mL of CH ₂ Cl ₂ . The mixture is stirred for 1 h at 0 ° C and then added dropwise with ice cooling, a solution of 1.4 mL (17 mmol) of pyrrolidine in 10 mL CH ₂ Cl ₂ . The The reaction mixture is warmed to RT overnight, mixed with water, the organic phase separated, this washed twice with water, filtered through activated charcoal and concentrated in vacuo. The residue is coevaporated twice with toluene and the product obtained is further reacted without purification. Yield: 2.25 g (95.9% of theory) C | ₃ Hι ₅ BrN ₂ (M = 279.18) calc .: Mole peak (M + H) +: 279/281 F: Mol peak (M + H) +: 279/281

Rr value: 0.5 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

2.107e. 2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine

To a solution of 225 mg (0.81 mmol) (3-bromo-4-pyrrolidin-1-ylmethylphenyl) acetonitrile in 5 mL methanolic NH ₃ and 5 mL EtOAc is added 20 mg Raney nickel and 1 h at RT and Shake 5 psi H ₂ in Parr autoclave. The catalyst is filtered off, the solvents are concentrated under reduced pressure and the product is reacted further without purification. Yield: 225 mg (98.1% of theory) C ₁₃ H ₉ BrN ₂ (M = 283.21) calc .: Mol peak (M + H) +: 283/285 F: Mol peak (M + H) + : 283/285

Rr value: 0.08 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

2.107f. 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide hydrochloride

Prepared according to general procedure I from 220 mg (0.78 mmol) 2- (3

Bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 186 mg (0.8 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. After removal of the drying agent and solvent, the residue is taken up in isopropanol / tert-butyl methyl ether, treated with ethereal HCl and concentrated in vacuo. The residue is again in

20 mL of isopropanol, triturated, filtered off, washed with a little isopropanol and dried at 50 ° C. Yield: 165 mg (39.6% of theory)

C26H27BrCl ₂ N ₂ O (M = 534.33) calc .: Mol peak (M + H) +: 497/499/501 Found: Mol peak (M + H) +: 497/499/501

Rr value: 0.35 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1). Example 2.108:

4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

To a suspension of 150 mg (0.28 mmol) 4'-chlorobiphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide hydrochloride in 5 mL dioxane 17.3 mg (0.28 mmol) of methyl boronic acid, 2.5 ml of 2M Na ₂ CO ₃ solution and 32 mg (0.03 mmol) of tetrakis (triphenylphosphine) palladium, and the reaction mixture was refluxed for 5 hours. The hot suspension is filtered off with suction through a glass fiber filter, the filtrate is mixed with semisaturated NaHCO ₃ solution, exhaustively extracted with EtOAc and dried over MgSO ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (CH ₂ Cl ₂ / MeOH 8: 2). Yield: 20 mg (. 16.4% of theory) C27H ₂ gcin ₂ 0 (M = 433.0) calc .: molecular peak (M + H) +: 433/435 Found .: molecular peak (M + H) +: 433/435 retention time HPLC: 6.47 min (Method A)

Example 2.109:

4'-Chloro-biphenyl-4-carboxylic acid [2- (2-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.109a. 4- (2-Amino-ethyl) -3-nitro-benzoic acid ethyl ester

To a -5 ° C cooled solution of 12.0 g (52 mmol) 4- (2-amino-ethyl) - benzoic acid ethyl ester in 80 mL conc. H ₂ S0 are portionwise 5.78 g (57 mmol) KN0 _{3 was} added and stirred at this temperature for 1 h. The reaction solution is slowly added dropwise to ice water (the temperature should not exceed 0 ° C) and stirred for 1 h. The precipitate is filtered off with suction, washed with water and dried at 50.degree. Yield: 8.2 g (66.2% of theory) C 1 - | H ₁₄ N ₂ O (M = 238.25) calc .: Mol peak (M + H) +: 239 found: Mol peak (M + H) +: 239 retention time HPLC: 3.64 min (Method A)

2.109b. Ethyl 4- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -3-nitrobenzoate

Prepared according to general procedure I from 8.2 g (34 mmol) 4- (2-

Amino-ethyl) -3-nitro-benzoic acid ethyl ester and 7.91 g (34 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. Yield: 7.7 g (50.0% of theory)

C ₂₄ H2iClN θ5 ₂ (M = 452,90) calc .: molecular peak (M + H) +: 452/454 Found .: molecular peak (M + H) +: 452/454

Retention time HPLC: 6.14 min (Method B)

2.109c. 3-Amino-4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid ethyl ester

To a solution of 7.7 g (17 mmol) of ethyl 4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} -3-nitrobenzoate in 200 mL EtOAc is added 0.5 g of Raney Nickel and shaking the reaction mixture in an autoclave overnight at RT and 10 psi H ₂ . To complete the reaction, 50 mL of THF are added and shaken for a further 2 h. The catalyst is filtered off, washed well with THF, the solvent was concentrated in vacuo, the residue triturated with EtOAc, filtered off with suction and dried in air. Yield: 5.0 g (69.5% of theory) of C2 ₄ H ₂₃ CIN ₂ 0 ₃ (M = 422.92) calc .: Mol peak (M + H) +: 423/425 Found: Mol peak (M + H ) +: 423/425

Retention time HPLC: 5.71 min (Method B) 2.109d. 3-Bromo-4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid ethyl ester

To a solution of 5.0 g (7.69 mmol) of ethyl 3-amino-4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} benzoate in 20 mL of water are added 20 mL of 48% HBr added and cooled to 0 ° C. Subsequently, a solution of 0.9 g (13 mmol) of NaN0 ₂ in 5.2 mL of water is added dropwise so that the temperature does not exceed 5 ° C and stirred for 10 min at 0 ° C after. Then a solution of 1.87 g (13 mmol) of CuBr in 6.65 mL 48% HBr is added dropwise rapidly at this temperature. The reaction mixture is then heated for 1 h at 60 ° C. Water is added and exhaustively extracted with EtOAc. The organic phase is washed with water and dried over MgS0. After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (petroleum ether / EtOAc 6: 4). Yield: 1.3 g (34.7% of theory) of C ₂ H 1 BrCINO ₃ (M = 486.80) calc .: Mol peak (M + H) +: 486/488/490 found: mol peak (M + H ) +: 486/488/490

Rr value: 0.55 (silica gel, petroleum ether / EtOAc 6: 4).

2.109e. 3-Bromo-4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid To a suspension of 1.3 g (2.67 mmol) 3-bromo-4- {2- [ (4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid ethyl ester in 20 mL EtOH and 5 mL THF are added 6 mL 1 N NaOH solution and the reaction mixture is stirred overnight at RT. It is concentrated in vacuo, the residue is mixed with water and neutralized with 1 N HCl, whereby the product precipitates. The mixture is stirred for a further hour under ice-cooling, filtered off with suction, washed with water and the product is dried at 50 ° C. Yield: 1.2 g (97.9% of theory) C ₂ 2H- | 7BrCINO ₃ (M = 458.74) calc .: Mol peak (M + H) +: 456/458/460 Found: Mol peak (M + H) +: 456/458/460 retention time HPLC: 5.51 min (method B)

2.109f. 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-bromo-4-hydroxymethyl-phenyl) -ethyl] -amide To a solution of 1.2 g (2.62 mmol) of 3-bromo-4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid in 10 mL of DMF is added 0.64 g (3.92 mmol ) CDI and heated to 50 ° C until the end of gas evolution. The reaction mixture is added to a solution of 0.3 g (7.85 mmol) of NaBH ₄ in 10 mL of water, stirred for 1 h at RT, made acidic with dilute KHSO solution and exhaustively extracted with EtOAc. The organic phase is washed with half-saturated NaHC0 ₃ solution and dried over MgS0. After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 0.87 g (74.8% of theory) of C ₂ H ₂ BrClCINO ₂ (M = 444.76) calc .: Mole peak (M + H) +: 444/446/448 F: Mol peak (M + H) + : 444/446/448

Retention time HPLC: 8.07 min (Method A)

2.109g. 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-bromo-4-chloromethyl-phenyl) -ethyl] -amide

To a solution of 0.87 g (1.96 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (2-bromo-4-hydroxymethyl-phenyl) -ethyl] -amide in 20 mL of CH ₂ Cl ₂ is added 0.24 mL ( 2.93 mmol) of pyridine and cooled to 0 ° C. 0.21 mL (2.93 mmol) of thionyl chloride are added, the mixture is stirred at this temperature for 1 h and then allowed to warm to rt. Water is added, filtered through Celite, the aqueous phase is extracted with CH ₂ Cl ₂ and the combined organic phases are dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 0.66 g (72.8% of theory) of C ₂ 2H- | ₈ BrCl2NO (M = 463.21) calc .: Mol peak (M + H) +: 462/464/466 found: Mol peak (M + H) +: 462/464/466 retention time HPLC: 6.37 min (Method B)

2.109h. 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

To a solution of 0.66 g (1.43 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (2-bromo-4-chloromethyl-phenyl) -ethyl] -amide in 20 mL acetonitrile and 6 mL DMF 0.59 g (4.28 mmol) of K ₂ C0 ₃ and 0.24 mL (2.85 mmol) of pyrrolidine are added and the mixture is stirred at RT for 5 h. It is mixed with water, extracted exhaustively with EtOAc, the organic phase is washed several times with water and dried over MgSÜ. ₄ After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (CH ₂ Cl ₂ / MeOH 9: 1). Yield: 0.2 g (28.2% of theory) C26 26 ^BrCIN 2θ ( ^M = 497.87) calc .: Mole peak (M + H) +: 497/499/501 found: Mol peak (M + H) + : 497/499/501

Retention time HPLC: 4.39 min (Method B)

Example 2.110:

4'-Chloro-biphenyl-4-carboxylic acid [2- (2-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 2.108 from 200 mg (0.40 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (2-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide and 27.3 mg (0.44 mmol ) Methyl boronic acid, with refluxing for only 2 h and the product is purified via HPLC. Yield: 62 mg (35.6% of theory) C ₂ 7H ₂ CIN ₂ O (M = 433.0) calc .: Mol peak (M + H) +: 433/435 Found: Molepeak (M + H) +: 433/435

Retention time HPLC: 6.15 min (Method A)

Example 2.111:

4'-Chloro-biphenyl-4-carboxylic acid [2- (2-nitro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.111a. 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -3-nitro-benzoic acid To a solution of 200 mg (0.44 mmol). 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -3-nitro-benzoic acid ethyl ester (Example 2.109b) in 10 mL EtOH, 2 mL 1N NaOH solution are added and the reaction mixture Stirred for 1 h at RT. It is concentrated in vacuo, the residue is combined with water and 2 ml of 1N HCl solution and the suspension is stirred for 30 minutes in an ice bath. The product is filtered off with suction, washed with water and dried at 50.degree. Yield: 180 mg (95.9% of theory) C22H17CIN2O5 (M = 424.84) calc .: Mol peak (M + H) +: 425/427 found: Mol peak (M + H) +: 425/427

Rr value: 0.07 (silica gel, EtOAc / MeOH / NH ₃ 9: 1: 0.1).

2.111b. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-hydroxymethyl-2-nitro-phenyl) -ethyl] -amide

Prepared analogously to Example 2.109f from 180 mg (0.42 mmol) of 4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} -3-nitrobenzoic acid.

Yield: 110 mg (63.1% of theory) C22H1 gCIN ₂ 0 ₄ (M = 410.86) calc .: Mol peak (M + H) +: 411/413 found: Mol peak (M + H) +: 411/413

Retention time HPLC: 8.27 min (method A)

2.111c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-nitro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

To a cooled to 5 ° C solution of 110 mg (0.27 mmol) of 4'-chloro-biphenyl-4-carboxylic acid [2- (4-hydroxymethyl-2-nitro-phenyl) -ethyl] -amide and 48 μL triethylamine in 5 mL of CH ₂ Cl ₂ are slowly added dropwise 23 μL methanesulfonyl chloride. The solution is heated to 40 ° C. for 1 h, 5 ml of DMF and 115 μL (1.34 mmol) of pyrrolidine are added and the mixture is heated at 80 ° C. for a further hour, the Evaporated off CH ₂ CI ₂ . The reaction mixture is concentrated under reduced pressure, the residue is combined with water, exhaustively extracted with EtOAc and the organic phase is dried over MgSO ₄ . After removal of the drying agent and solvent, the residue is purified by HPLC. Yield: 11 mg (8.8% of theory) ^C 26 26 ^CIN 3 ° 3 (= 463.97) calc .: Mol peak (M + H) +: 464/466 F: Mol peak (M + H) + : 464/466

Retention time HPLC: 6.44 min (Method A)

Example 2.112:

4'-Chloro-biphenyl-4-carboxylic acid [2- (2-methanesulfonylamino-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.112a. Ethyl 4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} -3-methanesulfonylaminobenzoate

To a cooled to 0 ° C solution of 200 mg (0.47 mmol) 3-amino-4- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzoic acid ethyl ester (Example 2.109c) in 5 ml of pyridine 44 μL (0.57 mmol) of methanesulfonyl chloride are slowly added dropwise and the reaction mixture stirred for 1 h at RT. It is mixed with ice water, extracted exhaustively with EtOAc, the organic phase is washed several times with water and dried over MgSθ ₄ . After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 230 mg (97.1% of theory) C25H25CIN2O5S (M = 501, 01) calc .: Mol peak (M + H) +: 501/503 found: Mol peak (M + H) +: 501/503

Retention time HPLC: 5.66 min (method B)

2.112b. 4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -3-methanesulfonylaminobenzoic acid Prepared analogously to Example 2.111a from 230 mg (0.46 mmol) of ethyl 4- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} -3-methanesulfonylaminobenzoate. Yield: 180 mg (82.9% of theory) ^c 23 ^H 2lCIN ₂ O ₅ S (M = 472.95)

Calc .: Molpeak (M-H) ": 471/473 Found: Molepeak (M-H)": 471/473 Retention Time HPLC: 7.67 min (Method A)

2.112c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-hydroxymethyl-2-methanesulfonylamino-phenyl) -ethyl] -amide Prepared analogously to Example 2.109f from 180 mg (0.38 mmol) of 4- {2 - [(4 ' -Chlorobiphenyl-4-carbonyl) -amino] -ethyl} -3-methanesulfonylaminobenzoic acid. Yield: 150 mg (85.8% of theory) of C ₂₃ H _{2 3} CIN ₂ 0 ₄ S (M = 458.97) calc .: Mole peak (M + H) +: 459/461 m.p .: Mol peak (M + H) +: 459/461 retention time HPLC: 7.53 min (method A)

2.112d. 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-methanesulfonylamino-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 2.111c from 150 mg (0.33 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (4-hydroxymethyl-2-methanesulfonylamino-phenyl) -ethyl] -amide and 140 μL (1.64 mmol) of pyrrolidine.

After purification via HPLC, the product is obtained as a formate salt. Yield: 18 mg (. 9.9% of theory) C27H ₃ OCIN ₃ 0 ₃ S ^* CH ₂ θ2 (M = 558.10) calc .: molecular peak (M + H) +: 512/514 Found .: molecular peak ( M + H) +: 512/514

Retention time HPLC: 6.13 min (Method A)

Example 2.113:

4'-Chloro-biphenyl-4-carboxylic acid [2- (3-pyridin-4-yl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared analogously to Example 2.108 from 200 mg (0.40 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide and 74 mg (0.60 mmol ) Pyridine-4-boronic acid, the product being purified via HPLC. Yield: 13 mg (6.5% of theory) of C ₃ ιH ₃₀ CIN ₃ O (M = 496.06) calc .: Mole peak (M + H) +: 496/498 Found: Mole peak (M + H) +: 496/498

Retention time HPLC: 6.37 min (method A)

Example 2.114:

5- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -2-pyrrolidin-1-ylmethyl-benzoic acid methyl ester

2.114a. 5-cyanomethyl-2-pyrrolidin-1-ylmethyl-benzoic acid methyl ester

To a solution of 500 mg (1.79 mmol) (3-bromo-4-pyrrolidin-1-ylmethylphenyl) acetonitrile (Example 2.107d) in 10 mL MeOH and 10 mL DMF are added 0.5 mL triethylamine (3.58 mmol), 40 mg (0:18 mmol) of Pd (OAc) ₂ and 99 mg given (0:18 mmol) of 1,1 ^{'-Diphenylphosphino-ferrocene.} The reaction mixture is stirred in an autoclave with 2 bar CO for 15 h at 50 ° C. To complete the reaction again 0.5 mL of triethylamine, 40 mg of Pd (OAc) ₂ and 99 mg of 1, 1 '- diphenylphosphino-ferrocene added, a further 10 h at 50 ° C and 2 bar CO and overnight at 4 bar CO and 70 ° C stirred. The solvents are in vacuo The residue is combined with EtOAc and extracted twice with water.

The aqueous phase is saturated with K ₂ C0 ₃ , exhaustively extracted with EtOAc and dried over MgS0. After removal of the drying agent and solvent, the product remains as a black oil, which is further reacted without purification.

Yield: 380 mg (82.1% of theory).

Cl5Hι ₈ N 0 ₂ (M = 258.32) calc .: Mol peak (M + H) +: 259 Found: Mol peak (M + H) +: 259

Retention time HPLC: 2.49 min (Method B)

2.114b. Methyl 5- (2-aminoethyl) -2-pyrrolidin-1-ylmethylbenzoate To a solution of 380 mg (1.47 mmol) of methyl 5-cyanomethyl-2-pyrrolidin-1-ylmethylbenzoate in 20 ml of methanolic NH ₃ are added 100 mg Raney nickel and hydrogenated the reaction mixture at 20 psi H _{2 for} 27 h at RT. The catalyst is filtered off with suction, the solvent stripped off and the residue is reacted further without purification. Yield: 330 mg (85.5% of theory). C15H22N2O2 (M = 262.36) calc .: Mol peak (M + H) +: 263 found: Mol peak (M + H) +: 263 retention time HPLC: 1.40 min (Method A)

2.114c. Methyl 5- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} -2-pyrrolidin-1-ylmethylbenzoate

Prepared according to general procedure I from 330 mg (1.26 mmol) of methyl 5- (2-aminoethyl) -2-pyrrolidin-1-ylmethylbenzoate and 293 mg (1.26 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. Yield: 315 mg (52.5% of theory) of C2 ₈ H ₂ gCIN ₂ 0 ₃ (M = 477.01) Calculated: Mol peak (M + H) +: 477/479 F: Mol peak (M + H ) +: 477/479 retention time HPLC: 6.82 min (method A) Example 2.115:

5- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -2-pyrrolidin-1-ylmethyl-benzoic acid

Hergestellt analog Beispiel 2.111a aus 310 mg (0.65 mmol) 5-{2-[(4'-Chlor- biphenyl-4-carbonyl)-amino]-ethyl}-2-pyrrolidin-1-ylmethyl- benzoesäuremethylester. Ausbeute: 85 mg (28,2 % d. Theorie) ^c27^H27^CIN2θ3 ( = 462,98) ber.: Molpeak (M+H)+: 463/465 gef.: Molpeak (M+H)+: 463/465

Prepared analogously to Example 2.111a from 310 mg (0.65 mmol) of methyl 5- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] -ethyl} -2-pyrrolidin-1-ylmethylbenzoate. Yield: 85 mg (28.2% of theory) ^c 27 ^H 27 ^CIN 2 O 3 (= 462.98) calc .: Mol peak (M + H) +: 463/465 found: mol peak (M + H) +: 463/465

Retention time HPLC: 6.30 min (Method A)

Example 2.116:

(5- {2 - [(4 ^, -chlorobiphenyl-4-carbonyl) -amino] -ethyl} -2-pyrrolidin-1-ylmethyl-phenyl) -carbamic acid tert -butyl ester

To a solution of 740 mg (1.6 mmol) of 5- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -2-pyrrolidin-1-ylmethylbenzoic acid in 10 mL of tert. Butanol is added 0.27 mL (1.92 mmol) of triethylamine and 0.41 mL (1.92 mmol) of diphenyl azido-phosphoric acid ester and the reaction mixture heated under reflux for 5 h. It is concentrated in vacuo, the residue is combined with CH ₂ Cl ₂ , extracted with 1 N NaOH solution and the organic phase is dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel. Yield: 85 mg (28.2% of theory) C ₃₁ H ₃₆ CIN ₃ 0 ₃ (M = 534.10) calc .: Mole peak (M + H) +: 534/536 Found: Mol peak (M + H ) +: 534/536

Retention time HPLC: 4.82 min (method B)

Example 2.117:

4'-Chloro-biphenyl-4-carboxylic acid [2- (3-ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.117a. (4-Pyrrolidin-1-ylmethyl-3-trimethylsilanylethynyl-phenyl) -acetonitrile A suspension of 0.36 g (1.29 mmol) of (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -acetonitrile (Example 2.107d), 0.36 mL (2.58 mmol) trimethylsilylacetylene, 0.36 mL (2.58 mmol) triethylamine, 25 mg (0.13 mmol) Cul and 0.15 g (0.13 mmol) tetrakis (triphenylphosphine) palladium in 3 mL DMF is added in the microwave (CEM) for 15 min stirred at 100 ° C and 200 watts. After cooling the reaction mixture is mixed with saturated NaCl solution, extracted exhaustively with EtOAc and the organic phase dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (EtOAc). Yield: 50 mg (13.1% of theory) C ₈ H ₂₄ N ₂ Si (M = 296.49) calc .: Mol peak (M + H) +: 297 F: Mol peak (M + H) +: 297

Retention time HPLC: 6.39 min (method A)

2.117b. 2- (3-Ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine To a solution of 50 mg (0.17 mmol) (4-pyrrolidin-1-ylmethyl-3-trimethylsilanylethynyl-phenyl) -acetonitrile in 5 mL methanolic NH ₃ is added 20 mg Raney nickel and the reaction mixture for 22 h at RT and 3 bar H ₂ shaken. The catalyst is filtered off with suction and the solvent removed in vacuo. The crude product is reacted further without purification. Yield: 39 mg (100% of theory) C 15 H ₂₄ N ₂ (M = 232.37) calc .: Mol peak (M + H) +: 233 F: Mol peak (M + H) +: 233

2.117c. 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 40 mg (0.17 mmol) of 2- (3-ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 48 mg (0.21 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. Yield: 2 mg (2.6% of theory) C ₂₈ H ₃ ιCIN ₂ O (M = 447.03) calc .: Mol peak (M + H) +: 447/449 found: mol peak (M + H) +: 447/449 retention time HPLC: 6.87 min (method A)

Example 2.118:

4'-Chloro-biphenyl-4-carboxylic acid [2- (6-pyrrolidin-1-ylmethyl-pyridin-3-yl) -ethyl] -amide

2.118a. 6-dibromomethyl-nicotinate

To a solution of 38.96 g (0.25 mol) of 6-methyl-nicotinic acid methyl ester in 1 L

CCl ₄ , 53.4 g (0.3 mol) of NBS and 2 g of dibenzoyl peroxide are added and the reaction mixture heated under reflux overnight. Then another 26.7 g (0.15 mol) of NBS and 1 g of dibenzoyl peroxide are added and heated again under reflux for 24 h. After cooling the reaction mixture, the precipitate is filtered off with suction, the solvent is stripped off and the residue is purified by chromatography. Yield: 15.0 g (19.4% of theory) C ₈ H ₇ Br ₂ Nθ ₂ (M = 308.96) calc .: Mol peak (M + H) +: 308/310/312 Found: Mol peak (M + H) +: 308/310/312

Rr value: 0.6 (silica gel, petroleum ether / EtOAc 8: 2).

2.118b. 6-dimethoxymethyl-nicotinate

13.9 mL NaOMe in MeOH (30%, 75 mmol) in 100 mL MeOH are heated to boiling. A solution of 11.0 g (34.1 mmol) of methyl 6-dibromomethyl-nicotinate in 10 ml of MeOH is added dropwise to the boiling solution and the mixture is heated under reflux overnight. To complete the reaction, another 1.5 mL (8.1 mmol) of the NaOMe solution are added and heated under reflux for a further 24 h. The reaction mixture is concentrated under reduced pressure, the residue is treated with dilute KHSO ₄ solution, neutralized with dilute NaHCO ₃ solution, exhaustively extracted with EtOAc, the organic phase is washed with water and dried over MgSO 4. After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 5.0 g (69.5% of theory) C ₁₀ Hι ₃ NO ₄ (M = 211.22) calc .: Mol peak (M + H) +: 212 F: Mol peak (M + H) +: 212

R _f value: 0.44 (silica gel, petroleum ether / EtOAc 6: 4).

2.118c. 6-dimethoxymethyl-nicotinic acid

To a solution of 2.8 g (13.26 mmol) of 6-Dimethoxymethyl- nicotinic acid methyl ester in 50 ml MeOH 15 mL 1N NaOH solution are added and stirred at RT. The reaction mixture is neutralized with 15 ml of 1N HCl, concentrated in vacuo, the residue triturated with MeOH / THF, the precipitate was filtered off with suction and the filtrate was concentrated. The product obtained is reacted further without purification. Yield: 2.6 g (99.4% of theory) C ₉ H ₁ - _| N0 ₄ (M = 197.19) calc .: Mol peak (M + H) +: 198 found: Mol peak (M + H) +: 198

Retention time HPLC: 3.65 min (method A)

2.118d. (6-dimethoxymethyl-pyridin-3-yl) -methanol Prepared analogously to Example 2.109f from 2.7 g (13.7 mmol) of 6-Dimethoxymethyl- nicotinic acid, wherein THF as a solvent and part. Butyl methyl ether is used for extraction. Yield: 2.1 g (83.7% of theory) CgH ₁₃ N0 ₃ (M = 183.21) calc .: Mol peak (M + H) +: 184 F: Mol peak (M + H) +: 184

Retention time HPLC: 2.85 min (method A)

2.118e. 5-Chloromethyl-2-dimethoxymethyl-pyridine To a solution of 500 mg (2.73 mmol) (6-dimethoxymethyl-pyridin-3-yl) -methanol in 10 ml CH ₂ Cl ₂ , cooled to 0 ° C, is added 0.3 mL (4.14 mmol ) Thionyl chloride, dissolved in a little CH ₂ Cl ₂ , slowly added dropwise and stirred for a further 30 min at this temperature. The reaction mixture is diluted with CH ₂ Cl ₂ , washed with cold NaHC0 ₃ solution and dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is reacted further without purification.

Yield: 500 mg (90.8% of theory) CgH ₁₂ CINO 2 (M = 201, 65) calc .: Mole peak (M + H) +: 202/204 Found: Molepeak (M + H) +: 202 / 204 R _f value: 0.3 (silica gel, petroleum ether / EtOAc 6: 4).

2.118f. (6-dimethoxymethyl-pyridin-3-yl) -acetonitrile

20 mL DMSO are added to 5.21 g (80 mmol) KCN in 5.2 mL water, and at 80 ° C. a solution of 500 mg (2.48 mmol) 5-chloromethyl-2-dimethoxymethylpyridine in 10 mL DMSO is added dropwise and the reaction mixture becomes a held at 80 ° C for an additional hour. It is poured into 200 ml of water, saturated with NaCl, extracted exhaustively with EtOAc, the organic phase is dried over MgS0 and filtered through activated charcoal. The filtrate is concentrated and the residue is purified by chromatography on silica gel (CH ₂ Cl ₂ / MeOH 9: 1). Yield: 330 mg (. 69.2% of theory) Cι ₀ H ₁₂ N ₂ θ2 (M = 192.22) calc .: molecular peak (M + H) +: 193 Found .: molecular peak (M + H) +: 193

Rr value: 0.48 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1). 2.118g. 2- (6-Dimethoxymethyl-pyridin-3-yl) -ethylamine To a solution of 330 mg (1.72 mmol) of (6-dimethoxymethyl-pyridin-3-yl) -acetonitrile in 10 mL of methanolic NH ₃ is added 50 mg of Raney nickel and hydrogenated the reaction mixture in Parr autoclave at 30 ° C for 15 h under 3 bar H ₂ . The catalyst is filtered off, the solvent is concentrated in vacuo and the residue is reacted further without purification. Yield: 340 mg (100% of theory) Cι ₀ Hι ₆ N ₂ θ2 (M = 196.25) calc .: Mol peak (M + H) +: 197 F: Mol peak (M + H) +: 197

Retention time HPLC: 1.3 min (Method A)

2.118h. 4'-Chloro-biphenyl-4-carboxylic acid [2- (6-dimethoxymethyl-pyridin-3-yl) -ethyl] -amide Prepared according to general procedure I from 340 mg (1.73 mmol) of 2- (6-dimethoxymethyl-pyridine 3-yl) ethylamine and 419 mg (1.80 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. Yield: 210 mg (28.4% of theory) of C2 ₃ H ₂₃ CIN ₂ 0 ₃ (M = 410.90) calc .: Mol peak (M + H) +: 411/413 Found: Mol peak (M + H ) +: 411/413

Rr value: 0.4 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

2.118i. 4'-Chloro-biphenyl-4-carboxylic acid [2- (6-formylpyridin-3-yl) -ethyl] -amide To a solution of 205 mg (0.5 mmol) 4'-chlorobiphenyl-4-carboxylic acid [ 2- (6-dimethoxymethyl-pyridin-3-yl) -ethyl] -amide in 10 mL MeOH 5 mL 12% HCl are added and the reaction mixture stirred for 4 h at RT and heated to 80 ° C overnight. It is again 2.5 mL 12% HCl, heated for a further 8 h at 80 ° C and overnight at 100 ° C. The reaction mixture is mixed with 50 ml of water, brought to pH 8 with Na ₂ CO ₃ solution, extracted exhaustively with CH ₂ Cl ₂ and the organic phase is dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 180 mg (98.7% of theory) ^c 2l Hi7CIN 0 ₂ (M = 364.84) Calc .: Molpeak (M + H) +: 365/367 Found: Molepeak (M + H) +: 365/367

Retention time HPLC: 5.25 min (method A)

2.118k. 4'-Chloro-biphenyl-4-carboxylic acid [2- (6-pyrrolidin-1-ylmethyl-pyridin-3-yl) -ethyl] -amide

To a solution of 180 mg (0.49 mmol) of 4'-chlorobiphenyl-4-carboxylic acid [2- (6-formylpyridin-3-yl) ethyl] -amide in 5 mL acetonitrile is added 50 μL (0.6 mmol). Pyrrolidine, 37.7 mg (0.6 mmol) of NaBH ₃ CN and 2 mL of MeOH, the pH was adjusted to 5-6 with glacial acetic acid and stirred at RT for 5 h. The reaction mixture is acidified with 1M KHSO solution, made alkaline with 2M Na ₂ C0 ₃ solution, exhaustively extracted with CH ₂ Cl ₂ and the organic phase dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel (CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1). Yield: 25 mg (12.1% of theory) C ₂ 5H ₂ 6CIN ₃ O (M = 419.96) calc .: Mol peak (M + H) +: 420/422 Found: Mol peak (M + H) +: 420/422

Rr value: 0.2 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

Example 2.119: 4'-Chloro-biphenyl-4-carboxylic acid [2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -ethyl] -amide

2.119a. Methyl 6-hydroxymethyl-nicotinate Prepared analogously to Example 2.109f from 5.0 g (27.6 mmol) of pyridine-2,5-dicarboxylic acid 5-methyl ester, THF being used as the solvent and tert-butyl methyl ether for the extraction. Yield: 2.0 g (43.3% of theory) C ₈ HgN0 ₃ (M = 167.17) calc .: Mol peak (M + H) +: 168 F: Mol peak (M + H) +: 168 Rr value: 0.2 (silica gel, CH ₂ Cl ₂ / MeOH 95: 5).

2.119b. 6-chloromethyl-nicotinic acid methyl ester

To a cooled to 0 ° C solution of 2.0 g (11.96 mmol) 6-hydroxymethyl-nicotinic acid methyl ester in 100 mL CH ₂ Cl ₂ are added 1.06 mL (13 mmol) of pyridine and slowly added dropwise 1.08 mL (13 mmol) of thionyl chloride. The mixture is stirred for a further hour at 0 ° C and then allowed to warm slowly to RT. To complete the reaction, another 1 mL (12 mmol) of thionyl chloride are added and the mixture is stirred at RT for 1 h. The reaction mixture is treated with water, the organic phase separated, washed with dilute NaHCO this solution and water and dried over MgS0. ₄ It is filtered through activated carbon and the solvent is concentrated in vacuo. The product obtained is reacted further without purification. Yield: 1.7 g (65.1% of theory) C ₈ H ₈ CIN 0 (M = 185.61) calc .: Mole peak (M + H) +: 186/188 F: Mol peak (M + H) +: 186/188

Retention time HPLC: 6.7 min (Method A)

2.119c. Methyl 6-cyanomethyl-nicotinate Prepared analogously to Example 2.118f from 1.5 g (8.08 mmol) of 6-chloromethyl-nicotinic acid methyl ester and 5.2 g (80 mmol) of KCN, using cyclohexane / EtOAc 8: 2 as the eluent for chromatographic purification on silica gel.

Yield: 220 mg (15.5% of theory) C ₉ H ₈ N ₂ O ₂ (M = 176.18) calc .: Mole peak (M + H) +: 177 F: Mol peak (M + H) + : 177

R, value: 0.6 (silica gel, petroleum ether / EtOAc 1: 1).

2.119d. Methyl 6- (2-aminoethyl) nicotinate 20 mg of Raney nickel are added to a solution of 75 mg (0.43 mmol) of 6-cyanomethyl-nicotinic acid methyl ester in 5 ml of methanolic NH ₃ and the reaction mixture in a Parr autoclave at 30 ° C. Hydrogenated under 3 bar H _{2 for} 6 h. Of the Catalyst is filtered off, the solvent is concentrated in vacuo and the residue is reacted further without purification. Yield: 70 mg (90.3% of theory) CgH ₁₂ N ₂ O ₂ (M = 180.21) calc .: Mol peak (M + H) +: 181 F: Mol peak (M + H) +: 181

Retention time HPLC: 2.5 min (method A)

2.119e. Methyl 6- {2 - [(4'-chlorobiphenyl-4-carbonyl) amino] ethyl} nicotinic acid Prepared according to general procedure I from 70 mg (0.39 mmol) of 6- (2-aminoethyl) nicotinic acid methyl ester and 100 mg (0.43 mmol) of 4'-chlorobiphenyl-4-carboxylic acid.

Yield: 150 mg (88.3% of theory) of C ₂ H ₂ CIN ₂ 0 ₃ (M = 394.86) Calculated by: Mole peak (M + H) +: 395/397 Found: Molepeak (M + H) +: 395/397 retention time HPLC: 8.6 min (method A)

2.119f. 6- {2 - [(4'-chloro-biphenyl-4-carbonyl) -amino] -ethyl} -nicotinic acid

To a solution of 150 mg (0.38 mmol) of methyl 6- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -nicotinate in 25 mL MeOH is added 0.8 mL 1 M NaOH solution and the reaction mixture heated under reflux for 1 h. It is neutralized with 0.8 ml of 1N HCl, concentrated in vacuo, the residue is stirred with water and filtered off with suction, the precipitate. This is dissolved in THF, the solution is dried with MgSO 4, filtered and concentrated in vacuo. The residue is reacted further without purification. Yield: 90 mg (62.2% of theory) of C ₂ H ₇ CIN ₂ O ₃ (M = 380.83) calc .: Mole peak (M + H) +: 381/383 found: mol peak (M + H) +: 381/383

Retention time HPLC: 6.9 min (Method A)

2.119g. 4'-Chloro-biphenyl-4-carboxylic acid [2- (5-hydroxymethyl-pyridin-2-yl) -ethyl] -amide Prepared analogously to Example 2.109f from 90 mg (0.24 mmol) of 6- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -nicotinic acid using THF as solvent and tert-butyl methyl ether for extraction becomes. Yield: 50 mg (56.8% of theory) 5 C ₂ 1 H- | 9CIN2O2 (M = 366.85) calc .: Mol peak (M + H) +: 367/369 found: Mol peak (M + H) +: 367/369

Rr value: 0.5 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1).

2.119h. 4'-Chloro-biphenyl-4-carboxylic acid [2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -o-ethyl] -amide

To a cooled to 0 ° C solution of 50 mg (0.14 mmol) of 4'-chloro-biphenyl-4-carboxylic acid [2- (5-hydroxymethyl-pyridin-2-yl) -ethyl] -amide in 5 mL CH ₂ Cl ₂ are added dropwise 22 μL thionyl chloride and the reaction mixture is allowed to warm slowly to RT. After 1 h at RT 5 further 22 μL thionyl chloride are added dropwise to complete the reaction and stirred for 1 h. The

The reaction mixture is diluted with 30 ml of CH ₂ Cl ₂ , mixed with ice-water, made alkaline with NaHCO ₃ solution, the organic phase is separated, this is washed with water and dried over MgS0. After removal of the drying agent, 50 μL (0.6 mmol) of pyrrolidine are added to this solution, and the reaction mixture is stirred at RT overnight. It is concentrated in vacuo and the residue is purified by HPLC chromatography. Yield: 2.4 mg (4.1% of theory) C ₂ 5H ₂ 6CIN ₃ O (M = 419.96) calc .: Mol peak (M + H) +: 420/422 found: Mol peak (M + H) +: 420/422 5 R _f value: 0.3 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1). Retention time HPLC: 6.0 min (Method A)

Example 2.120:

4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -amide

2.120a. [2- (4-Acetyl-phenyl) -ethyl] -carbamic acid tert-butyl ester To a solution of 4.99 g (25 mmol) of 1- [4- (2-amino-ethyl) -phenyl] -ethanone (used as hydrochloride ) in 100 ml of CH ₂ Cl ₂ are added 5.46 g (25 mmol) of BOC anhydride and slowly added dropwise at RT 25 mL of 1 N NaOH solution and stirred for 2 h at RT after completion of the addition. The reaction mixture is filtered through Celite, washed twice with water and dried over MgS0 ₄ . It is filtered through activated charcoal, concentrated in vacuo and the product is further purified without purification.

Yield: 6.4 g (97.2% of theory) of C ₅ H ₂ i NO ₃ (M = 263.34) calc .: Mole peak (M + H) +: 262 m.p .: Mol peak (M + H) +: 262

Rr value: 0.88 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

2.120b. {2- [4- (1-Hydroxyethyl) phenyl] -ethyl} -carbamic acid tert-butyl ester To a solution of 6.58 g (25 mmol) of [2- (4-acetyl-phenyl) -ethyl] -carbamic acid tert-butyl ester in 250 ml of MeOH at RT 4.72 g (125 mmol) of NaBH ₄ are added in portions and the reaction mixture was stirred over the weekend. The mixture is acidified carefully with KHS0 ₄ solution and extracted exhaustively with tert-butyl methyl ether, the organic phase is washed with saturated NaCl solution and dried over MgSθ. ₄ After removal of the drying and Lösungsmitteis the product remains as a pale yellowish oil, which crystallized on standing. Yield: 5.4 g (81.4% of theory) of C ₅ H ₂₃ N0 ₃ (M = 265.36) calc .: Mole peak (M + H) +: 266 F: Mol peak (M + H) +: 266

Rr value: 0.4 (silica gel, petroleum ether / EtOAc 6: 4). 2.120c. {2- [4- (1-Pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -carbamic acid tert-butyl ester To a cooled to 0 ° C solution of 2.89 g (10.89 mmol) of {2- [4- (1-hydroxy-ethyl) -phenyl] -ethyl} -carbamic acid tert-butyl ester in 50 mL CH ₂ CI ₂ and 25.1 ml of triethylamine 0.66 mL (8.5 mmol) of methanesulfonyl chloride dissolved in 10 mL CH ₂ CI _2, was added dropwise. The mixture is stirred for 1 h at this temperature and then allowed to a solution of 1.4 mL (17 mmol) of pyrrolidine in 10 mL CH ₂ Cl ₂ slowly added dropwise. The reaction mixture is stirred overnight at RT, treated with dilute KHS0 ₄ - solution, the organic phase separated, washed twice with dilute KHS0 ₄ solution, the combined aqueous phases with K ₂ Cθ ₃ solution made basic and tert-butyl methyl ether extracted exhaustively. The combined organic phases are washed several times with a little water and dried over MgS0 ₄ . After removal of the drying agent and solvent, the product is reacted further without purification. Yield: 0.3 g (8.7% of theory) Ci gH ₃₀ N ₂ O ₂ (M = 318.46) calc .: Mol peak (M + H) +: 319 F: Mol peak (M + H) +: 319

Rr value: 0.22 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 9: 1: 0.1).

2.120d. 2- [4- (1-Pyrrolidin-1-yl-ethyl) -phenyl] -ethylamine To a solution of 300 mg (0.94 mmol) of {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl ] - ethyl} -carbamic acid tert-butyl ester in 20 mL CH ₂ Cl ₂ are added 0.72 mL trifluoroacetic acid and stirred for 1 h at RT. To complete the reaction, 0.72 ml of trifluoroacetic acid are again added and the reaction mixture is kept at RT for 1 h. The solvent is concentrated in vacuo, the residue taken up in water, made alkaline with 2 N NaOH, exhaustively extracted with EtOAc and the organic phase over MgS0 ₄ dried. After removal of the drying agent and solvent, the product is further reacted without purification. Yield: 150 mg (72.9% of theory) C ₁ H ₂ 2N ₂ (M = 218.35) calc .: Mol peak (M + H) +: 219 F: Mol peak (M + H) +: 219

Rr value: 0.15 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2). 2.120e. 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -amide

Prepared according to general procedure I from 150 mg (0.69 mmol) of 2- [4-

(1-pyrrolidin-1-yl-ethyl) -phenyl] -ethylamine and 176 mg (0.76 mmol) of 4'-chlorobiphenyl-4-carboxylic acid.

Yield: 150 mg (88.3% of theory)

C27H ₂ gcin ₂ 0 (M = 433.0) calc .: molecular peak (M + H) +: 433/435 Found .: molecular peak (M + H) +: 433/435

Retention time HPLC: 6.33 min (Method A)

Example 2.121:

4'-Chloro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide

2.121a. [4- (2-Amino-ethyl) -2-bromo-phenyl] -methanol To a solution of 4 g (17.68 mmol) of (3-bromo-4-hydroxymethyl-phenyl) -acetonitrile (see Example 2.107c.) In 100 mL of THF and 50 mL of methanolic NH ₃ are added to 100 mg of Raney nickel and the reaction mixture is shaken in a Parr autoclave for 5 h at RT and 5 psi H ₂ . The catalyst is filtered off, the solvent is stripped off and the product is reacted further without purification. Yield: 3.8 g (93.4% of theory) CgH- | 2BrNO (M = 230.11) calc .: Mol peak (M + H) +: 230/232 Found: Mol peak (M + H) +: 230 / 232 Retention time HPLC: 1.85 min (method A)

2.121b. [2- (3-Bromo-4-hydroxymethyl-phenyl) -ethyl] -carbamic acid tert -butyl ester To a solution of 3.8 g (16.51 mmol) of [4- (2-aminoethyl) -2-bromo-phenyl] - Methanol in 50 mL CH ₂ Cl ₂ 17 mL of a 1 M BOC anhydride solution in CH ₂ Cl ₂ and the reaction mixture was stirred overnight at RT. you diluted with 100 mL of dilute KHS0 ₄ solution, the organic phase is separated off, washed with dilute NaHCO ₃ solution and water and dried over MgSO ₄ . After removal of the drying agent and solvent, the residue is purified by chromatography on silica gel. Yield: 2.3 g (42.2% of theory) of C ₄ H ₂ oBrNO ₃ (M = 330.22)

Rr value: 0.44 (silica gel, petroleum ether / EtOAc 6: 4).

2.121c. [2- (3-Bromo-4-chloromethyl-phenyl) -ethyl] -carbamic acid tert-butyl ester To a solution of 1.98 g (6.0 mmol) of [2- (3-bromo-4-hydroxymethyl- phenyl) -ethyl] -carbamic acid tert-butyl ester in 50 mL CH ₂ Cl ₂ and 0.53 mL pyridine are slowly added dropwise 0.54 mL (6.5 mmol) of thionyl chloride, stirred for a further hour at 0 ° C and then warmed to RT. The reaction mixture is treated with water, the organic phase washed with dilute KHS0 ₄ solution and water and dried over MgS0. ₄ After

Filtration over activated charcoal and removal of the solvent, the product is further reacted without purification. Yield: 2.0 g (95.6% of theory) of C ₄ H ₁₉ BrCINO 2 (M = 348.67) calc .: Mole peak (M + H) +: 348/350/352 found: mol peak (M + H) +: 348/350/352

R _f value: 0.6 (silica gel, petroleum ether / EtOAc 6: 4).

2.121d. {2- [3-Bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -carbamic acid tert-butyl ester To a suspension of 1.9 g (5.45 mmol) of [2- (3 -Bromo-4-chloromethyl-phenyl) - ethyl] -carbamic acid tert-butyl ester and 2.5 g (18.1 mmol) K ₂ C0 ₃ in 50 mL acetonitrile are 0.84 mL (11 mmol) of 2,5-dihydro-1 H-pyrrole added and the reaction mixture stirred at RT overnight. The suspension is filtered, the filtrate concentrated in vacuo and the residue purified by chromatography on silica gel.

Yield: 0.5 g (24.1% of theory) C-] ₈ H25BrN 0 ₂ (M = 381, 32) calc .: Mol peak (M + H) +: 381/383 found: mol peak (M + H) +: 381/383 Rr value: 0.58 (silica gel, CH ₂ Cl ₂ / MeOH 8: 2).

2.121e. 2- [3-Bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethylamine To a solution of 500 mg (1.31 mmol) of {2- [3-bromo-4- (2, 5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -carbamic acid tert-butyl ester in 50 ml of CH ₂ Cl ₂ , 5 ml of trifluoroacetic acid are added and the reaction mixture is stirred at RT for 2 h. It is concentrated in vacuo, mixed with water and CH ₂ Cl ₂ , an alkaline pH with K ₂ C0 ₃ solution, the organic phase is separated off and washed again with water. It is concentrated in vacuo and the product is purified by chromatography on silica gel.

Yield: 350 mg (95.0% of theory) of Cι ₃ Hι ₇ BrN ₂ (M = 281, 20) Calculated: Mol peak (M + H) +: 281/283 Found: Molpeak (M + H) + : 281/283

Rr value: 0.08 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 95: 5: 0.5).

2.121 f. 4'-Chloro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-yl-methyl) -phenyl] -ethyl} -amide

Prepared according to general procedure I from 141 mg (0.5 mmol) of 2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethylamine and 116 mg (0.5 mmol) of 4'- chloro-biphenyl-4-carboxylic acid.

Yield: 140 mg (56.5% of theory.) C ₂ 6H24BrCIN ₂ 0 (M = 495.85) calc .: molecular peak (M + H) +: 495/497/499 Found .: molecular peak (M + H) +: 495/497/499

Retention time HPLC: 6.6 min (method A)

Example 2.122:

4'-Bromo-3-fluoro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-yl-methyl) -phenyl] -ethyl} -amide

2.122a. 4'-Brom-3-fluor-biphenyl-4-carbonsäure

2.122a. 4'-bromo-3-fluoro-biphenyl-4-carboxylic acid

To a solution of 1.1 g (5 mmol) 4-bromo-2-fluorobenzoic acid in 5 mL DMF and 5 mL dioxane are successively 1.04 g (5 mmol) of 4-bromophenylboronic, 115 mg (0.1 mmol) tetrakis (triphenylphosphine) palladium and 2 ml of 2M Na ₂ C0 ₃ - solution and the reaction mixture heated under reflux for 2 h. To complete the reaction, 250 mg (1.25 mmol) of 4-bromophenylboronic acid are added again and the mixture is heated under reflux for a further 2 hours. The reaction mixture is filtered hot through a Giasfaserfilter, washed with water, acidified with dilute KHS0 ₄ solution, the resulting precipitate was filtered off with suction and washed with water. The residue is triturated with acetonitrile and a little MeOH, filtered from insolubles, the filtrate is concentrated, the residue is triturated with MeOH and the product is filtered off with suction. Yield: 140 mg (9.5% of theory) C | ₃ H ₈ BrF0 ₂ (M = 295.11) calc .: Mol peak (M + H) +: 293/295 Found: Mol peak (M + H) +: 293/295

Rr value: 0.5 (silica gel, CH ₂ Cl ₂ / MeOH 9: 1).

2.122b. 4'-Bromo-3-fluoro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide Prepared according to the general procedure I from 141 mg (0.5 mmol) 2- [3- bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethylamine and 140 mg (0.47 mmol) 4'-bromo-3-fluoro biphenyl-4-carboxylic acid. Yield: 10 mg (3.8% theory d.) C26 ^H 23Br2 ^FN 2θ (M = 558.29) calc .: molecular peak (M + H) +: 557/559/561 Found .: molecular peak (M + H) +: 557/559/561

Retention time HPLC: 7.0 min (method A)

Example 2.123:

4'-Chloro-biphenyl-4-carboxylic acid [2- (3-amino-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

To a solution of 40 mg (0.08 mmol) of (5- {2 - [(4'-chlorobiphenyl-4-carbonyl) -amino] -ethyl} -2-pyrrolidin-1-ylmethyl-phenyl) -carbamic acid-tert -butyl ester (see Example 2.116) in 3 mL CH ₂ Cl ₂ are added 0.12 mL trifluoroacetic acid and the reaction mixture is stirred over the weekend at RT. It is concentrated in vacuo, mixed with semisaturated NaHC0 ₃ solution, extracted with EtOAc and the organic phase is dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is purified by HPLC. Yield: 3 mg (7.3% of theory)

^C 26 ^H 28 ^CIN 3 ° * ^C 2 ^F 3 ° 2 (M = 548.01) calc .: Mol peak (M + H) +: 434/436 found: Mol peak (M + H) +: 434/436

Retention time HPLC: 5.35 min (Stable Bond C18, 3.5 μM, water: acetonitrile: formic acid 6: 4: 0.015)

Example 2.124:

4'-Chloro-biphenyl-4-carboxylic acid ethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.124a. Ethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine To a solution of 204 mg (1.0 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 0.17 ml of triethylamine in 5 mL THF, a solution of 89 .mu.L (1.1 mmol) of ethyl iodide in 1 mL THF is added dropwise and the reaction mixture is stirred for 24 h at RT. It is mixed with saturated NaHC0 ₃ solution, extracted with EtOAc and The organic phase is dried over MgS0 ₄ . After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 70 mg (30.1% of theory).

2.124b. 4'-Chloro-biphenyl-4-carboxylic acid ethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 70 mg (0.3 mmol) of ethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 81 mg (0.35 mmol) of 4'-chlorobiphenyl-4- carboxylic acid. Yield: 20 mg (14.9% of theory) C2 ₈ H ₃₁ CIN ₂ O (M = 447.03) calc .: Mole peak (M + H) +: 447/449 found: mol peak (M + H) +: 447/449

Retention time HPLC: 6.92 min (Method A)

Example 2.125:

4'-Chloro-biphenyl-4-carboxylic acid-isobutyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.125a. Isobutyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine

A solution of 204 mg (1.0 mmol) 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 91 μL (1.0 mmol) isobutyraldehyde in 20 mL THF is slightly acidified with glacial acetic acid, with 253 mg (1.2 mmol) NaBH (OAc) ₃ and stirred overnight at RT. The reaction mixture is mixed with half-saturated NaHC0 ₃ solution, exhaustively extracted with EtOAc; the aqueous phase is saturated with K ₂ CO ₃ and extracted with EtOAc. The combined organic phases are dried over MgS0. After removal of the drying agent and solvent, the residue is reacted further without purification. Yield: 250 mg (96.0% of theory). C ₇ H ₂₈ N 2 (M = 260.43) Calc .: Molpeak (M + H) +: 261 Found: Molepeak (M + H) +: 261

Rr value: 0.4 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2).

2.125b. 4'-Chloro-biphenyl-4-carboxylic acid isobutyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 250 mg (0.96 mmol) isobutyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 244 mg (1.05 mmol) 4'-chlorobiphenyl-4- carboxylic acid. Yield: 67 mg (14.7% of theory) C ₃ oH ₃₅ CIN ₂ 0 (M = 475.08) calc .: Mol peak (M + H) +: 475/477 found: mol peak (M + H) +: 475/477

Retention time HPLC: 7.67 min (method A)

Example 2.126: 4'-Chloro-biphenyl-4-carboxylic acid-cyclohex-3-enylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.126a. Cyclohex-3-enylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine Prepared analogously to Example 2.125a. from 204 mg (1.0 mmol) 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 114 / L (1.0 mmol) 1, 2,3,6-

Tetrahydrobenzaldehyde.

Yield: 100 mg (33.5% of theory).

C20H30 2 (M = 298.48) R _f value: 0.2 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2).

2.126b. 4'-Chloro-biphenyl-4-carboxylic acid-cyclohex-3-enylmethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 100 mg (0.34 mmol) of cyclohex-3-enylmethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 86 mg (0.37 mmol) of 4'-chloro biphenyl-4-carboxylic acid. Yield: 46 mg (26.8% of theory) C ₃₃ H ₃₇ CIN 0 (M = 513.13) calc .: Mol peak (M + H) +: 513/515 Found: Mol peak (M + H) + : 513/515

Retention time HPLC: 8.20 min (Method A)

Example 2.127: 4'-Chloro-biphenyl-4-carboxylic acid benzyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.127a. Benzyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine Prepared analogously to Example 2.125a. from 204 mg (1.0 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 102 / L (1.0 mmol) of benzaldehyde. Yield: 160 mg (54.3% of theory). C ₂₀ H ₂ 6N ₂ (= 294.44)

Rr value: 0.28 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2).

2.127b. 4'-Chloro-biphenyl-4-carboxylic acid benzyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 160 mg (0.54 mmol)

Benzyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 140 mg (0.60 mmol) of 4'-chlorobiphenyl-4-carboxylic acid.

Yield: 16 mg (5.8% of theory)

^C ₃₃ H ₃₃ CIN ₂ O (M = 509.10) calc .: Mol peak (M + H) +: 509/511 Found: Mol peak (M + H) +: 509/511

Retention time HPLC: 7.51 min (Method A) Example 2.128:

4'-Chloro-biphenyl-4-carboxylic acid cyclohexylmethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.128a. Cyclohexylmethyl-[2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-amin Hergestellt analog Beispiel 2.125a. aus 204 mg (1.0 mmol) 2-(4-Pyrrolidin-1- ylmethyl-phenyl)-ethylamin und 121 μL (1.0 mmol) Cyclohexancarbaldehyd. Ausbeute: 100 mg (33,3 % d. Theorie). C2θH₃2N2 (M= 300,49) R_f-Wert: 0.18 (Kieselgel, CH₂CI₂/MeOH/NH₃ 8:2:0.2).

2.128a. Cyclohexylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine Prepared analogously to Example 2.125a. from 204 mg (1.0 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 121 μL (1.0 mmol) of cyclohexanecarbaldehyde. Yield: 100 mg (33.3% of theory). C2θH ₃ 2N2 (M = 300.49) R _f value: 0.18 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2).

2.128b. 4'-Chloro-biphenyl-4-carboxylic acid cyclohexylmethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

Prepared according to general procedure I from 100 mg (0.33 mmol) of cyclohexylmethyl [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 86 mg (0.37 mmol) of 4'-chlorobiphenyl-4- carboxylic acid. Yield: 70 mg (40.8% of theory) C ₃₃ H ₃₃ CIN ₂ 0 (M = 515.15) calc .: Mole peak (M + H) +: 515/517 Found: Molepeak (M + H) +: 515/517 retention time HPLC: 8.63 min (method A)

Example 2.129:

4'-Chloro-biphenyl-4-carboxylic acid-cyclopropylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide

2.129a. Cyclopropylmethyl-[2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-amin Hergestellt analog Beispiel 2.125a. aus 204 mg (1.0 mmol) 2-(4-Pyrrolidin-1- ylmethyl-phenyl)-ethylamin und 75 μL (1.0 mmol) Cyclopropancarbaldehyd. Ausbeute: 100 mg (38,7 % d. Theorie). Cι₇H₂6N2 (M= 258,41)

2.129a. Cyclopropylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine Prepared analogously to Example 2.125a. from 204 mg (1.0 mmol) of 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine and 75 μL (1.0 mmol) of cyclopropanecarbaldehyde. Yield: 100 mg (38.7% of theory). C ₇ H ₂ 6 N ₂ (M = 258.41)

Rr value: 0.30 (silica gel, CH ₂ Cl ₂ / MeOH / NH ₃ 8: 2: 0.2).

2.129b. 4'-Chloro-biphenyl-4-carboxylic acid-cyclopropylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide Prepared according to general procedure I from 100 mg (0.39 mmol) cyclopropylmethyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amine and 100 mg (0.43 mmol) of 4'-chlorobiphenyl-4-carboxylic acid. Yield: 23 mg (12.6% of theory) C ₃₀ H ₃₃ CIN ₂ O (M = 473.06) calc .: Mol peak (M + H) +: 473/475 found: Mol peak (M + H) +: 473/475

Retention time HPLC: 7.45 min (method A)

Example 2.130:

4-pentyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol) and 4-pentyl-benzoic acid (96 mg, 0.50 mmol). Yield: 75 mg (39.6% of theory) C 25 H 34 N 2 O (M = 378.56) calc .: Mol peak (M + H) +: 379 F: Mol peak (M + H) +: 379

Retention time HPLC: 6.5 min (Method A)

Example 2.131: 4-butyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol) and 4-butyl-benzoic acid (89 mg, 0.50 mmol).

Yield: 60 mg (32.9% of theory)

C24H ₃ 2N2θ (M = 364.54) calc .: molecular peak (M + H) +: 365 Found .: molecular peak (M + H) +: 365

Retention time HPLC: 6.0 min (Method A)

Example 2.132:

4-butylamino-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethylphenyl) ethylamine (204 mg, 1.0 mmol) and 4-butylaminobenzoic acid (155 mg, 0.80 mmol).

Yield: 30 mg (9.9% of theory) of C ₂ H ₃₃ N ₃ O (M = 379.55) calc .: Mole peak (M + H) +: 380 F: Mol peak (M + H) +: 380

Retention time HPLC: 6.0 min (Method A)

Example 2.133:

4- (1-methyl-butyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (82 mg, 0.40 mmol) and 4- (1-methyl-butyl) -benzoic acid (75 mg, 0.39 mmol). Yield: 40 mg (27.1% of theory) of C2 ₄ H ₃₂ N ₂ O (M = 378.56) calc .: Mol peak (M + H) +: 379 F: Mol peak (M + H) +: 379

Retention time HPLC: 4.3 min (Method B)

Example 2.134:

Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4- (4,4,4-trifluoro-butoxy) -benzamide

2.134a. Methyl 4- (4,4,4-trifluoro-butoxy) benzoate To a solution of 304 mg (2.0 mmol) of 4-hydroxybenzoic acid methyl ester in 10 mL of DMF are added 608 mg (4.4 mmol) of K ₂ CO ₃ and then 382 mg (2.0 mmol) 1-bromo-4.4.4-trifluorobutane. The mixture is stirred overnight at RT, treated again with 1-bromo-4.4.4-trifluorobutane and stirred for a further 24 h at RT.

The reaction solution is diluted with water and exhaustively extracted twice with EtOAc. The united org. Extracts are dried over MgS0 and i. vac. concentrated. The crude product is used without further purification in the subsequent reaction step.

Yield: 500 mg (95.3% of theory)

C ₁₂ H ₁₃ F ₃ O ₃ (M = 262.23) calc .: Mol peak (M + H) ⁺ : 263 found: Mol peak (M + H) ⁺ : 263

Rr value: 0.9 (silica gel, petroleum ether / EtOAc 6: 4). 2.134b. 4- (4,4,4-trifluoro-butoxy) -benzoic acid

To a solution of 500 mg (1.9 mmol) 4- (4,4,4-trifluoro-butoxy) -benzoic acid methyl ester in 7 mL THF are added 10.0 mL (10.0 mmol) 1 M sodium hydroxide solution. The mixture is stirred at reflux for 8 h. THF becomes i. vac. removed and the residue acidified with hydrochloric acid. The resulting precipitate is dried after filtration in air. Yield: 350 mg (73.9% of theory) C ₁ H ₃ F ₃ O ₃ (M = 248.20) calc .: Mol peak (MH) ^" : 247 F: Mol peak (MH) -: 247 Retention time HPLC: 7.5 min (method A)

2.134c. Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -4- (4,4,4-trifluoro-butoxy) -benzamide

Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethylamine (102 mg, 0.50 mmol) and 4- (4,4,4-trifluorobutoxy) -benzoic acid (124 mg, 0.50 mmol). Yield: 37 mg (17.0% of theory) C ₂₄ H ₂ g F ₃ N ₂ O ₂ (M = 434.51) calc .: Mol peak (M + H) +: 435 F: Mol peak (M + H) +: 435 retention time HPLC: 5.8 min (method A)

Example 2.135:

3-methyl-4-pent-1-ynyl / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.135a. Methyl 3-methyl-4-pent-1-vinylbenzoate To a solution of methyl 4-bromo-3-methylbenzoate (458 mg, 2.0 mmol) in 3.0 mL DMF, 0.39 mL (4.0 mmol) pentyne, 0.56 mL (4.0 mmol) triethylamine, 70 mg (0.1 mmol) of bis (triphenylphosphine) palladium (II) chloride and 19 mg (0.1 mmol) of copper (I) iodide given. The reaction solution is stirred for 10 minutes at 200 watts and 65 ° C in the microwave. Another 0.20 mL (2.0 mmol) of pentin are added and the reaction solution is stirred for a further 20 minutes at 200 W and 70 ° C. in the microwave. The mixture is diluted with 30 mL EtOAc, filtered through Celite and the filtrate washed three times with 50 mL water. The combined organic extracts are dried over MgS0 ₄ , filtered through activated charcoal and the solvent i. vac. away. The purification is carried out by column chromatography on silica gel (cyclohexane after cyclohexane / ethyl acetate 9: 1). Yield: 200 mg (46.2% of theory) C ₁₄ H- | ₆ 0 ₂ (M = 216.28) calc .: Mol peak (M + H) ⁺ : 217 found: Mol peak (M + H) ⁺ : 217

Retention time HPLC: 6.8 min (Method B)

2.135b. 3-Methyl-4-pent-1-ynylbenzoic acid To a solution of 200 mg (0.93 mmol) of methyl 3-methyl-4-pent-1-ynylbenzoate in 3 ml of methanol are added 3.0 ml (3.0 mmol) of 1 M sodium hydroxide solution added. The mixture is stirred for 3 h at reflux. The reaction solution is diluted with water and extracted once with 40 mL EtOAc. The aqueous phase is acidified with 1 M KHSO ₄ solution and extracted twice with 40 mL EtOAc. The combined organic phases are dried over MgS0 ₄ . After removal of the drying agent and solvent, the crude product is used without further purification in the subsequent reaction step. Yield: 50 mg (26.7% of theory) C | ₃ H ₁₄ 0 ₂ (M = 202.26) calc .: Molpeak (MH) ^" : 201 Found: Molepeak (MH) ^" : 201

Retention time HPLC: 5.6 min (Method B)

2.135c. 3-Methyl-4-pent-1-ylinyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 2- (4-pyrrolidin-1-yl) ylmethylphenyl) ethylamine (51mg, 0.25mmol) and 3-methyl-4-pent-1-ynylbenzoic acid (50mg, 0.25mmol). Yield: 22 mg (22.9% of theory) C26 32 ^N 2 ° ( ^M = 388,558) calc .: Mol peak (M + H) +: 389 found: Mol peak (M + H) +: 389

Retention time HPLC: 6.9 min (Method A)

Example 2.136:

4-pent-1-ynyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.136a. Ethyl 4-pent-1-ynylbenzoate To a solution of 552 mg (2.0 mmol) of ethyl 4-iodobenzoate in 3 ml of DMF is added successively 0.39 ml (4 mmol) of 1-pentyne, 0.56 ml of triethylamine, 70 mg (0.1 mmol) of bismuth. (triphenyIphosphine) -palladium (II) chloride and 19 mg (0.1 mmol) of Cul. The reaction solution is stirred at 80 ° C for 4 h. The mixture is diluted with 30 mL EtOAc, filtered through Celite, the filtrate washed three times with 50 mL water and dried over MgS0. After filtration through activated charcoal, the solvent is removed in vacuo. The purification was carried out by column chromatography on silica gel (cyclohexane after cyclohexane / ethyl acetate 9: 1). Yield: 150 mg (34.7% of theory) C- | Hι ₆ 0 ₂ (M = 216,282) calc .: Mol peak (M + H) ⁺ : 217 F: Mol peak (M + H) ⁺ : 217

Retention time HPLC: 6.8 min (Method B)

2.136b. 4-Pent-1-ynylbenzoic acid To a solution of 150 mg (0.69 mmol) of ethyl 4-pent-1-yl-benzoate in 3 ml of methanol are added 5.0 ml (5.0 mmol) of 1M sodium hydroxide solution. The mixture is stirred for 3 h at reflux. The reaction solution is diluted with water and extracted once with 40 mL EtOAc. The aqueous phase is acidified with 1 M KHS0 ₄ solution and extracted twice with 40 mL EtOAc. The combined organic extracts are dried over magnesium sulfate and the solvent i. vac. away. The crude product was used without further purification in the subsequent reaction step. Yield: 150 mg (115% of theory) C- | ₂ Hi2θ2 (M = 188.23) calc .: Mol peak (MH) ^" : 187 found: Mol peak (MH) ^" : 187

Rr value: 0.2 (silica gel, petroleum ether / EtOAc 8: 2).

2.136c. 4-Pent-1-ynyl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl) ethylamine (163mg, 0.80mmol) and 4-pent-1-ynylbenzoic acid (150mg, 0.80mmol).

Yield: 122 mg (40.9% of theory) C ₂₅ H ₃₀ N 2 O (M = 374.53) calc .: Mol peak (M + H) +: 375 F: Mol peak (M + H) +: 375 Rf Value: 0.35 (silica gel, EtOAc / methanol / NH ₃ 9: 1: 0.1).

Example 2.137:

(4-pent-1-enyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

2.137a. 4-Pent-1-enyl-benzoic acid methyl ester

To a solution of 1.08 g (2.2 mmol) (4-methoxycarbonyl-benzyl) -triphenyl phosphonium bromide in 20 mL THF under an argon atmosphere at 0 ° C 246 mg (2.2 mmol) of potassium terf-butoxide added. The orange solution is stirred for a further 15 min at 0 ° C and then treated with 0.18 mL (2.0 mmol) butyraldehyde. The reaction solution is refluxed for 3 h and then diluted with EtOAc. The organic phase is washed twice with water, dried over magnesium sulfate and the solvent i. vac. away. The residue is triturated with diisopropyl ether, filtered and the filtrate is concentrated. Further purification is carried out by column chromatography on silica gel (petroleum ether / EtOAc 6: 4). There is obtained 4-pent-1-enyl-benzoic acid methyl ester as a 2: 1 E / Z isomer mixture. Yield: 350 mg (56.5% of theory) C ₁₃ H _{1 6} O ₂ (M = 204.27) calc .: Mole peak (M + H) ⁺ : 204 F: Mol peak (M + H) ⁺ : 204

Rr value: 0.90 (silica gel, petroleum ether / EtOAc 6: 4).

2.137b. 4-pent-1-enyl-benzoic acid

To a solution of 350 mg (1.71 mmol) of 4-pent-1-enyl-benzoic acid ethyl ester in 4 mL of methanol is added 5.0 mL (5.0 mmol) of 1 M sodium hydroxide solution. The

Mixture was stirred for 2 h at reflux. The solvent is i. vac. removed and the residue is treated with 6M hydrochloric acid solution. The resulting

Precipitate is filtered off and dried at 35 ° C in a convection oven.

Further purification is carried out by filtration through a silica gel column (petroleum ether / EtOAc 6: 4).

Yield: 300 mg (92.1% of theory)

Cι ₂ H ₁₄ 0 ₂ (M = 190.24) calc .: molecular peak (MH) ^': 189 Found .: molecular peak ^(MH)': 189

Rr value: 0.4 (silica gel, petroleum ether / EtOAc 6: 4).

2.137c. 4-pent-1-enyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide Prepared according to general procedure I from 2- (4-pyrrolidin-1-ylmethyl-phenyl ) -ethylamine (306 mg, 1.50 mmol) and 4-pent-1-enyl-benzoic acid (300 mg, 1.56 mmol) as a 2: 1 E / Z isomer mixture. Yield: 130 mg (23.0% of theory) C2δH ₃ 2N 0 (M = 376.547) calc .: Mol peak (M + H) +: 377 F: Mol peak (M + H) +: 377

Retention time HPLC: 6.9 min (Method A)

Example 2.138:

3-Chloro-4-cyclohexyl- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide

Prepared according to general procedure 1 from 2- (4-pyrrolidin-1-ylmethylphenyl) ethylamine (102 mg, 0.50 mmol) and 3-chloro-4-cyclohexylbenzoic acid

(119 mg, 0.50 mmol).

Yield: 46 mg (21.6% of theory)

C ₂ 6H ₃₃ CIN ₂ O (M = 425.019) calc .: Mol peak (M + H) +: 425/427 found: Mol peak (M + H) +: 425/427

Retention time HPLC: 4.7 min (Method B)

The following describes test methods for determining MCH receptor antagonist activity. In addition, further test methods known to the person skilled in the art, for example via the inhibition of the MCH receptor-mediated inhibition of cAMP production, as described by Hoogduijn M et al. in "Melanin-concentrating hormone and its receptor are expressed and functional in human skin", Biochem. Biophys. Res Commun. 296 (2002) 698-701 and the biosensing measurement of the binding of MCH to the MCH receptor in the presence of plasmon resonance antagonistic substances, as described by Karlsson OP and Lofas S. in "Flow-Mediated On-Surface Reconstitution of G-Protein Coupled Receptors for Applications in Surface Plasmon Resonance

Biosensors ", Anal. Biochem 300 (2002), 132-138.) Further test methods for MCH receptor antagonist activity are included in the introductory references and patent documents whose description of the test methods is hereby incorporated in this application.

MCH-1 receptor binding test

Method: MCH binding to hMCH-1 R transfected cells

Species: Human

Test cell: hMCH-1 R stably transfected in CHO / Galpha16 cells. Results: IC50 values Membranes from human hMCH-1R stably transfected CHO / Galpha16 cells are resuspended by syringe (0.6 x 25 mm needle) and assay buffer (50 mM HEPES, 10 mM MgCl ₂ , 2 mM EGTA, pH 7.00, 0.1%). Bovine serum albumin (protease-free), 0.021% bacitracin, 1 / g / ml aprotinin, 1 / g / ml leupeptin and 1 / M phosphoramidone) to a concentration of 5 to 15 // g / ml.

200 microliters of this membrane fraction (containing 1 to 3 μg of protein) are incubated for 60 minutes at room temperature with 100 pM ²⁵ L-tyrosyl melanin concentrating hormone ( ¹²⁵ I-MCH commercially available from NEN) and increasing concentrations of the test compound in a final volume of 250 microliters , After incubation, the reaction is filtered using 0.5% PEI-treated glass fiber filters (GF / B, Unifilter Packard) using a cell strainer. The membrane-bound radioactivity retained on the filter is then determined after addition of scintillator substance (Packard Microscint 20) in a measuring device (TopCount from Packard).

Non-specific binding is defined as bound radioactivity in

Presence of 1 micromolar MCH during the incubation period.

The analysis of the concentration-binding curve is performed assuming a

Receptor binding site. Default:

Unlabeled MCH competes with labeled ¹²⁵ I-MCH for receptor binding with an IC50 value between 0.06 and 0.15 nM. The KD value of the radioligand is 0.156 nM.

MCH-1 receptor-coupled Ca ²⁺ mobilization test

Method: Calcium mobilization test with human MCH (FLIPR ³⁸⁴ ) Species: Human

Test Cells: Stably-transfected CHO / Galpha 16 cells with hMCH-R1

Results:: 1. Measurement:% stimulation of the reference (MCH 10 ^"6 M)

2nd measurement: pKB value

Reagents: HBSS (10x) (GIBCO) HEPES buffer (1 M) (GIBCO)

Pluronic F-127 (Molecular Probes)

Fluo-4 (Molecular Probes)

Sample sathy (Sigma)

MCH (Bachern)

Bovine Serum Albumin (Serva)

(Protease free)

DMSO (Serva)

Ham's F12 (BioWhittaker)

FCS (BioWhittaker)

L-Glutamine (GIBCO)

Hygromycin B (GIBCO)

PENStrep (BioWhittaker)

Zeocin (Invitrogen)

Clonal CHO / Galpha16 hMCH-R1 cells are cultured in Ham's F12 cell culture medium (with L-glutamine; BioWhittaker; Cat. No .: BE12-615F). This contains per 500 ml of 10% FCS, 1% PENStrep, 5 ml L-glutamine (200 mM stock solution), 3 ml hygromycin B (50 mg / ml in PBS) and 1.25 ml Zeocin (100 // g / ml stock solution). One day prior to the experiment, the cells are plated on 384-well microtiter plate (black-walled with transparent bottom, manufacturer: Costar) at a density of 2500 cells per well and in the above-described medium overnight at 37 ° C, 5% C0 ₂ and 95% relative humidity cultured. On the day of the experiment, the cells are incubated with cell culture medium to which 2 mM Fluo-4 and 4.6 mM Probenicid are added at 37 ° C for 45 minutes. After loading with fluorescent dye, the cells are washed four times with Hanks buffer solution (1 × HBSS, 20 mM HEPES) supplemented with 0.07% Probenicid. The test substances are diluted in Hanks buffer solution, mixed with 2.5% DMSO. The background fluorescence of unstimulated cells is measured in the presence of substance in the 384-well microtiter plate five minutes after the last wash in the FLIPR ³⁸⁴ apparatus (Molecular Devices, excitation wavelength: 488 nm, emission length: bandpass 510 to 570 nm). For cell stimulation, MCH is diluted in Hanks buffer with 0.1% BSA, 35 minutes after the last wash to the 384-well cell culture plate pipetted and the MCH-stimulated fluorescence subsequently measured in the FLIPR ³⁸⁴ device.

Data analysis: 1st measurement: The cellular Ca ²⁺ mobilization is as a peak of the relative fluorescence minus the background and expressed as percentage of the maximum signal of the reference (MCH 10 ^"6 M) This measurement serves to identify any possible agonistic effect of a test substance.. 2nd measurement: the cellular Ca ²⁺ mobilization is as a peak of the relative fluorescence minus the background and measured as a percentage of the maximum signal of the reference (MCH 10 ^"6 M, signal is standardized to 100%), respectively. The EC50 values of the MCH dose-response curve with and without test substance (defined concentration) are determined graphically by the GraphPad Prism 2.01 curve program. MCH antagonists cause a right shift of the MCH stimulation curve in the generated graph.

The inhibition is expressed in pKB value: pKB = lθg (EC50 (test substance + CH) / ECso (CH) ^_ 1) "log C (test substance)

The compounds according to the invention, including their salts, exhibit an MCH receptor antagonistic action in the abovementioned tests. Using the MCH-1 receptor binding test described above is ^"to 10 ^{9" 6} M, obtain an antagonistic activity in a dose range of about 10 ^"10 to ^{10" 5} M, in particular of 10 degrees.

The following IC50 values were determined using the previously described MCH-1 receptor binding assay:

Compound according to example no. IC50

1.14 2.1 nM

2.4 3.5 nM

2.12 30.5 nM The following describes examples of administration forms in which the term "active ingredient" denotes one or more compounds according to the invention, including their salts. In the case of one of the combinations described with one or more further active substances, the term "active ingredient" also includes the other active substances.

Example 3

Capsules for powder inhalation with 1 mα active ingredient

Composition:

1 capsule for powder inhalation contains:

Active ingredient 1.0 mg lactose 20.0 mg

Hard gelatine capsules 50.0 mg

71.0 mg

Production method:

The active ingredient is ground to the particle size required for inhalation. The ground active substance is mixed homogeneously with the milk sugar. The mixture is filled into hard gelatin capsules.

Example 4

Inhalation solution for Respimat® with 1 mg active substance

Composition: 1 stroke contains:

Active ingredient 1.0 mg Benzalkonium chloride 0.002 mg

Disodium edetate 0.0075 mg

Water cleaned ad 15.0 μ \

Production method: The active ingredient and benzalkonium chloride are dissolved in water and filled into Respimat® cartridges.

Example 5

Inhalation solution for Vemebler with 1 mg active substance

Composition: 1 vial contains: active substance 0.1 g

Sodium chloride 0.18 g

Benzalkonium chloride 0.002 g

Water purified ad 20.0 ml

Production method:

Active substance, sodium chloride and benzalkonium chloride are dissolved in water.

Example 6

Propellant metered dose inhaler with 1 mg active substance

Composition: 1 stroke contains:

Active ingredient 1.0 mg

Lecithin 0.1% propellant ad 50.0 μ \

Production method:

The micronized drug is homogeneously suspended in the mixture of lecithin and propellant. The suspension is filled into a pressure vessel with metering valve.

Example 7

Nasalsprav with 1 mo active ingredient Composition:

Active ingredient 1.0 mg

Sodium chloride 0.9 mg

Benzalkonium chloride 0.025 mg Disodium edetate 0.05 mg

Water cleaned ad 0.1 ml

Production method:

The active ingredient and the excipients are dissolved in water and filled into a corresponding container.

Example 8

Injection solution with 5 mg of active substance per 5 ml

Composition:

Active substance 5 mg

Glucose 250 mg

Human serum albumin 10 mg

Glykofurol 250 mg

Water for injections ad 5 ml

production:

Glykofurol and glucose in water for injection dissolve (Wfl); Add human serum albumin; Dissolve active ingredient with heating; fill with Wfl to batch volume; Fill into ampoules under nitrogen fumigation.

Example 9

Injection solution with 100 mo of active substance per 20 ml

Composition:

Active substance 100 mg

Monopotassium dihydrogen phosphate = KH2P0 ₄ 12 mg

Disodium hydrogen phosphate = Na 2 HPO ₄ -2H 2 O 2 mg Sodium chloride 180 mg

Human serum albumin 50 mg

Polysorbate 80 20 mg

Water for injections ad 20 ml

production:

Dissolve polysorbate 80, sodium chloride, monopotassium dihydrogen phosphate and disodium hydrogen phosphate in water for injections (Wfl); Add human serum albumin; Dissolve active ingredient with heating; fill with Wfl to batch volume; fill in ampoules.

Example 10

Lvophilisate with 10 mg active substance

Composition:

Active substance 10 mg

Mannitol 300 mg

Human serum albumin 20 mg

production:

Dissolve mannitol in water for injections (Wfl); Add human serum albumin; Dissolve active ingredient with heating; fill with Wfl to batch volume; to fill in vials; freeze-dry.

Solvent for lyophilisate:

Polysorbate 80 = Tween 80 20 mg

Mannitol 200 mg

Water for injections ad 10 ml

Herstelluno:

Dissolve polysorbate 80 and mannitol in water for injections (Wfl); fill in ampoules. Example 11

Tablets with 20 mo of active substance

Composition:

Active substance 20 mg

Lactose 120 mg

Corn starch 40 mg

Magnesium stearate 2 mg

Povidone K 25 18 mg

production:

Mix active substance, lactose and maize starch homogeneously; granulate with an aqueous solution of povidone; mix with magnesium stearate; press on a tablet press; Tablet weight 200 mg.

Example 12

Capsules with 20 mg active substance

Composition:

Active substance 20 mg

Corn starch 80 mg

Silica, highly dispersed 5 mg

Magnesium stearate 2.5 mg

production:

Mix active substance, corn starch and silica homogeneously; mix with magnesium stearate; Fill mixture on a capsule filling machine into hard gelatin capsules size 3.

Example 13

Suppository with 50 mo of active substance

Composition:

Active substance 50 mg Hard fat (Adeps solidus) qs ad 1700 mg

production:

Melt hard fat at approx. 38 ° C; homogeneously disperse the ground active substance in the molten hard fat; after cooling to approx. 35 ° C pour into pre-cooled molds.

Example 14

Injection solution with 10 mg active substance per 1 ml

Composition:

Active substance 10 mg

Mannitol 50 mg

Human serum albumin 10 mg water for injections ad 1 ml

production:

Dissolve mannitol in water for injections (Wfl); Add human serum albumin; Dissolve active ingredient with heating; fill with Wfl to batch volume; Fill into ampoules under nitrogen fumigation.

Claims

claims 1. carboxamide compounds of the general formula I.

in the R ^1, R ² are independently H, an optionally substituted Cι ¹¹ _-8 alkyl or C ₃ -7-CycloalkyI group or an optionally monosubstituted with the group R by the group R ¹² or singly, multiply, and / or nitro substituted phenyl radical, or R ¹ and R ² form a C _2-8 alkylene bridge in which one or two -CH ₂ groups are independently -CH = N- or -CH = CH- may be replaced and / or one or two -CH ₂ groups can be replaced independently of one another by -O-, -S-, -CO-, -C (CHCH ₂ ) - or -NR ¹³ - such that heteroatoms are not directly linked to one another, wherein one or more H atoms in the above-defined alkylene bridge may be replaced by R ¹⁴ , and / or wherein the previously defined alkylene bridge may be substituted with one or two identical or different carbo- or heterocyclic groups Cy such that the bond between the alkylene bridge and the group Cy via a single or double bond, via a common C atom with formation of a spirocyclic ring system, via two common, adjacent C and / or N atoms to form a fused bicyclic ring system or - takes place via three or more C and / or N atoms to form a bridged ring system, ^R3 is H, Cι-6-alkyl, C _3-7 -CycloalkyI, C ₃ -7-cycloalkyl Cι- ₄ alkyl, C _3-7 - cycloalkenyl,

Phenyl, phenyl-Cι _-4 - alkyl-, Cι- ₃ -alkoxy-C ₂ - ₆ alkyl, amino-C _2-6 alkyl, Cι. _3- alkyl-amino-C ₂ -β-alkyl- or di- (C ₃ -alkyl) -amino-C ₂ - ₆ -alkyl-, X is a single bond or a _-8- alkylene bridge, in the - one or two -CH ₂ groups can be replaced independently of one another by -CH =CH- or -C≡C- and / or - one or two -CH groups independently of one another -O-, -S-, - (SO) -, - (S0 ₂ ) -, -CO- or -NR ⁴ - can be replaced such that in each case two O, S or N atoms or an O- are not directly connected with an S-atom, wherein one or two carbon atoms independently of one another with a hydroxy, co-hydroxy-C _1-3 -alkyl, ω- (-C ₃ -alkoxy) - C-ι- ₃ -alkyl and / or Cι _-3 Alkoxy radical and / or may be substituted in each case with one or two identical or different -C _-6- alkyl radicals, and / or wherein the alkylene bridge may be linked to R ¹ including the N atom joined to R ¹ and X to form a heterocyclic group, a Cι _-4 -alkylene bridge, wherein two adjacent carbon atoms may be connected to each other with an additional Cι _-4- alkylene bridge, wherein in the group Z is a -CH ₂ group by - O- or -NR ⁵ - can be replaced where one or two C atoms of the alkylene bridge independently of one another with a hydroxy ω-hydroxy-Cι-, ₃ alkyl, ω- (Cι-3-alkoxy) -C _1-3 alkyl, Cι _-3 alkoxy radical, amino-Cι _-3 alkyl, Cι _-3 alkyl-amino-Cι-3-alkyl or di- (Cι _-3 alkyl) amino-Cι _-3 -alkyI- and / or may be substituted with one or two identical or different Cι-β-alkyl radicals, and / or wherein R ^{3 may be} joined to Z including the N atom joined to R ³ to form a heterocyclic group, independently one of the Cy specified meanings wherein R ^{1 may be} joined to Y including the group X and the N atom joined to R ¹ and X to form a heterocyclic group fused to Y, and / or wherein R ^{3 may be} joined to Y including the group Z and the N atom connected to R ³ and Z to form a saturated or partially unsaturated heterocyclic group fused to Y, or where A and R ³ can be connected to each other in such a way that the group of formula I

a group of the partial formula II

means and Q is a group selected from the partial formulas IIIa to IIIg -CR ⁶ R ⁷ - IIIa -CR ^D = CR ⁷ lllb 8th -N = CR IIIc -N = N - IIIc -co- NR- llle

-CO- lllg L ¹ , L ² , L ^3, independently of one another, have the meanings given for R ²⁰ , B de alkyl, de-alkenyl, Cι- ₆ alkynyl, Cs ^ cycloalkyl-d-alkyl-, C _3-7 cycloalkenyl-Cι- ₃ alkyl, C ₃ - ₇ cycloalkyl-Cι- ₃ - alkenyl- or C ₃ -C ₇ -cycloalkyl-C _1-3 alkynyl, in which one or more C atoms are mono- or polysubstituted by halogen and / or simply by hydroxy or cyano and / or cyclic groups are mono- or polysubstituted by R ²⁰ may be substituted, or one of the meanings given for Cy, wherein the bond to the group W or optionally directly to the group A via a carbon atom of the carbocyclic part or the optionally fused phenyl or pyridine ring or via an N or C atom of the heterocyclic moiety, wherein for the case k = 0, the group B with the group A via a common carbon atom to form a spirocyclic ring system or can be connected to each other via two common, adjacent atoms to form a fused, bicyclic ring system, W is a single bond, -O-, a Cι _-4 alkylene, C2-4 alkenylene, C _2-4 alkynylene, Cι- alkyleneoxy, oxy-C-ι- alkylene-, Cι-Cι _-3 alkylene oxy _-3 alkylene-, imino, N- (Cι _-3 alkyl) -imino-, lmino-Cι _-4 - alkylene, N- (Cι _-3 alkyl) -imino-Cι-4-alkylene, Cι- alkylene-imino or Cι- _4- alkylene-N- (-C _3- alkyl) imino group, wherein one or two C atoms independently of one another with a hydroxy, ω-hydroxy-C ₃ -alkyl, ω- (C ₃ -alkoxy) -d-3-alkyl and / or C ₃ -alkoxy Rest and / or may be substituted with one or two identical or different Cι- ₆ alkyl radicals, and / or wherein W in the meanings alkylene, oxyalkylene and Alkylenoxyalkylen with B meaning Cy also has a Double bond may be associated k 0 or 1, Cy is a carbo or heterocyclic group selected from one of the following meanings a saturated 3- to 7-membered carbocyclic group, an unsaturated 5- to 7-membered carbocyclic group, a phenyl group, a saturated 4- to 7-membered or unsaturated 5- to 7-membered heterocyclic group having an N, O or S atom as heteroatom, a saturated or unsaturated 5- to 7-membered heterocyclic group having two or more N atoms or having one or two N atoms and one O or S atom as heteroatoms, an aromatic heterocyclic 5- or 6-membered group with one or more identical or different heteroatoms selected from N, O and / or S, wherein the above-mentioned 4-, 5-, 6- or 7-membered groups may be connected via two common, adjacent carbon atoms condensed with a phenyl or pyridine ring, and wherein in the aforementioned 5, 6 or 7-membered groups one or two non-adjacent -CH ₂ - groups by a - CO, -C (= CH ₂ ) -, - (SO) - or - (S0 ₂ ) Group can be replaced, and where the above-mentioned saturated 6- or 7-membered groups are also available as bridged ring systems with an imino, N- (C 1-6 -alkyl) -imino-, methylene-, (C 1-4 -alkyl) -methylene- or di ( Cι- ₄ alkyl) methylene bridge may be present, and where the abovementioned cyclic groups may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , and in the case of a phenyl group may also be additionally substituted simply by nitro, and / or by one or more N atoms with R ²¹ , R ⁴ , R ^5, independently of one another, have the meanings given for R ¹⁶ , R ⁶ , R ⁷ , R ^8, R ⁹ are independently H, a Cι _-6 alkyl, ω-Cι _-3 - _Alkoxy-3 Cι- alkyl or (o-hydroxy-Cι _-3 alkyl group and R ^6, R ^7, R ⁸ independently of one another can also be halogen, R ¹¹ R ¹⁵ -0-, R ¹⁵ -0-CO-, R ¹⁶ R ¹⁷ N-, R ¹⁸ R ¹⁹ N-CO- or Cy, R ^{12 is} one of the meanings given for R ²⁰ , R ^{13 is} one of the meanings given for R ¹⁷ , R ¹⁴ is halogen, C _1-6 alkyl, R ¹⁵ -0-, R ¹⁵ -0-CO-, R ¹⁶ R ¹⁷ N-, R ¹⁸ R ¹⁹ N-CO- , R ¹⁵ -O-C ₃ -alkyl, R ¹⁵ -O-CO-C _1-3 -alkyl, R ⁶ R ⁷ N-Cι_ ₃ -alkyl, R ¹⁸ R ¹⁹ N-CO-C _{3 -3} alkyl or Cy-C _1-3 -alkyl, R ¹⁵ is H, Cι- ₄ alkyl, C _3-7 cycloalkyl, C _3-7 cycloalkyl-Cι alkyl _-3, phenyl, Phenyl-C ₃ -alkyl or pyridinyl, R ¹⁶ H, de-alkyl, C _3-7 -cycloalkyl, C _3-7 -cycloalkyl-C _{3 -3} -alkyl-, C ₄ - ₇ - Cycloalkenyl, _C4 -7 cycloalkenyl Cι _-3 alkyl, ω-hydroxy-C2-3-alkyl, ω- (Cι _-3 alkoxy) -C2-3-alkyl-, amino alkyl--de- C 1 -C 3 -alkyl-amino-C 1 -C 6 -alkyl or di- (C 3 -alkyl) -amino-C 1 -C 6 -alkyl-, R ^{17 is} one of the meanings given for R ¹⁶ or Phenyl, phenyl-d _-3- alkyl, pyridinyl, dioxolan-2-yl, Cι. _3- alkylcarbonyl, hydroxycarbonyl -C. ₃ alkyl, Cι- ₄ alkoxycarbonyl, Cι _-3 alkylcarbonylamino-C ₂ - ₃ -alkyi-, Cι- ₃ alkylsulfonyl or Cι -AIkylsulfonylamino _{-3-C 2} - ₃ alkyl, R ¹⁸ , R ¹⁹ independently of one another denote H or d _-6- alkyl, R ²⁰ is halogen, hydroxy, cyano, _-4 alkyl, _C3 -7 cycloalkyl, hydroxy, d-3-alkyl, R ²² -Cι _-3 alkyl, or one of the meanings given for R ^22, R ^{21 is} ds-alkyl, ω-hydroxy-C ₂ . _3- alkyl, phenyl, phenyl-C _{3 -3} alkyl, C _1-3 Alkyl-carbonyl, carboxy, d-4-alkoxy-carbonyl, C _1-3 - alkylsulphonyl, phenylcarbonyl or phenyl-Cι _-3 alkyl-carbonyl, R ²² is pyridinyl, phenyl, phenyl-Cι _-3 -alkoxy, 3-alkoxy, Cι _-3 alkylthio, carboxy, H-CO-, Cι-3-alkylcarbonyl, Cι _-4 alkoxycarbonyl, Ami nocarbony I, Ci -3-AI ky lami nocarbonyl-, di (C _{3 -3} alkyl) aminocarbonyl, d _-3 alkyl sulfonyl, C _1-3 alkyl sulfinyl, Cι.3 Alkyl-sulfonylamino, amino, C 3 -alkylamino, di (C _{3 -3} -alkyl) amino, phenyl-C 3 -alkylamino or N- (C _{3 -3} -alkyl) phenyl-Cι 3-alkylamino, acetylamino, propionylamino, Phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxyalkylaminocarbonyl, (4-morpholinyl) carbonyl, (1-pyrrolidinyl) carbonyl, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl, (4 Methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonylamino or Alkylami nocarbony lami no- wherein in the groups and radicals A, B, W, X, Y, Z, R ¹ to R ⁹ and R ¹¹ to R ²² each one or more carbon atoms one or more times with F and / or in each case one or two C Atoms independently of one another can be substituted simply with Cl or Br, and / or in each case one or more phenyl rings independently of one another additionally one, two or three substituents selected from the group F, Cl, Br, I, Cι. _4- alkyl, d _-4 - alkoxy, difluoromethyl, trifluoromethyl, hydroxy, amino, Cι.3-alkylamino, di- (C ₃ -alkyl) -amino, acetylamino, aminocarbonyl, CN - Difluoromethoxy, trifluoromethoxy, _amino-3 Cι- alkyl, Cι _-3 alkylamino d-3-alkyl and include di- (Cι _-3 alkyl) amino-C _1-3 alkyl and / or may simply be substituted with nitro, and the H atom of an existing carboxy group or an H atom bound to an N atom can each be replaced by an in-vivo leaving group, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. 2. Carbonsäureamid compounds according to claim 1, characterized in that R ³ H, Cι. _6- alkyl, C _3-7 -cycloalkyl, C ₃ . ₇ -cycloalkyl-C _1-4 -alkyl-, Cι _-3 - Alkoxy-C ₂ - ₆ -alkyl, amino-C ₂ - ₆ -alkyl, C ₃ -alkyl-amino-C ₂ - ₆ -alkyl- or di- (C _{3 -3} -alkyl) -amino-C _{2 6-} alkyl, B is one of the meanings given for Cy, wherein the bond to the group W or optionally directly to the group A via a carbon atom of the carbocyclic part or the optionally fused phenyl or pyridine ring or via an N or C atom of the heterocyclic moiety he follows, wherein for the case k = 0, the group B with the group A via a common carbon atom to form a spirocyclic ring system or can be connected to each other via two common, adjacent atoms to form a fused, bicyclic ring system, R ¹⁵ H, d. _4- alkyl, C _3-7 -cycloalkyl, C ₃ -7-cycloalkyl-C _1-3 -alkyl, phenyl or phenyl-C. _3- alkyl, R ^{17 is} one of the meanings given for R ¹⁶ or Phenyl, phenyl-C ₃ -alkyl, dioxolan-2-yl, d. _3- alkylcarbonyl, hydroxycarbonyl -C. ₃ -alkyl, Cι. _3- Alkylcarbonylamino-C2. ₃ alkyl, Cι _-3 alkylsulphonyl or Cι- ₃ -Alkylsu! Fonylamino-C _2- 3-alkyl, R ²² is phenyl, phenyl-Cι _-3 alkoxy, d _-3 alkoxy, d _-3 alkylthio, carboxy, Cι-3-alkylcarbonyl, Cι _-3 alkoxycarbonyl, aminocarbonyl, d-3-alkylaminocarbonyl, di- (Cι _-3 alkyl) aminocarbonyl, d _-3 - alkyl-sulfonyl, Cι- alkyl sulfinyl ₃ - Cι _-3 alkyl-sulfonylamino, amino, Cι-3-alkylamino, di- (d _-3 alkyl) -amino, phenyl-Cι-3-- alkylamino or N- (Cι _-3 - Alkyl) -phenyl-C _1-3 -alkylamino, acetylamino, propionylamino, phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxyalkylaminocarbonyl, (4-morpholinyl) carbonyl-, (1-pyrrolidinyl) carbonyl-, ( 1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl, (4- Methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonylamino or alkylaminocarbonylamino, wherein in the groups A, B, W, X, Y, Z, R ¹ to R ⁹ and R ¹¹ to R ²² each one or more carbon atoms one or more times with F and / or each one or two carbon atoms independently of one another may simply be substituted by Cl or Br, and wherein the groups A, W, X, Y, Z, R ¹ , R ² , R ⁴ to R ⁹ , R ¹¹ to R ¹⁴ , R ¹⁶ and R ¹⁸ to R ²¹ and k have the meaning according to claim 1, and the H atom of an existing carboxy group or an H atom bound to an N atom can each be replaced by an in-vivo leaving group, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. Carboxylic acid amide compounds according to claim 1 or 2, characterized in that the group A has one of the meanings given for Cy in claim 1. Carboxylic acid amide compounds according to one or more of claims 1 to 3, characterized in that A and R ³ are connected together such that the group of the formula

a group of the partial formula II

means and Q is a group selected from the partial formulas IIIa to IIIg -CR ⁶ R ⁷ - IIIa -CR ^b = CR IIIb 8th -N = CR IIIc -N = N-III Cl-NR-IIle

CO lllg means, and L ¹ , L ² , L ³ , R ⁶ , R ⁷ , R ⁸ and R ^{9 have} the meanings given in claim 1. 5. Carboxylic acid amide compounds according to one or more of Claims 1 to 4, characterized in that R ^1, R ² are independently H, Ci-e-alkyl, C _3-7 cycloalkyl, C _3-7 cycloalkyl-Cι- ₃ alkyl, ω-hydroxy-C2 3-alkyl, o (C 1-3 -alkoxy) C 2-3 -alkyl, C 1-4 -alkoxycarbonyl-C ₁ . ₃ - alkyl, amino-C _2-alkyl, Cι-3-alkyl-amino-C ₂ -4-alkyl- or di- (Cι- ₃ alkyl) - _amino-C2-C4 alkyl, phenyl or phenyl-Cι mean _-3 alkyl, wherein in the groups and radicals given above one or more C atoms may be mono- or polysubstituted with F and / or one or two C atoms independently of one another can be substituted simply with Cl or Br, and where the phenyl radical may be mono- or polysubstituted by the radical R ¹² defined in claim 1 and / or simply by nitro. 6. Carbonsäureamid compounds according to one or more of claims 1 to 4, characterized in that R ¹ and R ² such a Alkylene bridge according to claim 1, that R ¹ R ² N- is a group selected from azetidine, pyrrolidine, piperidine, azepane, 2,5-dihydro-1 H-pyrrole, 1, 2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepinyl, 2,3,6,7-tetrahydro-1H-azepines, piperazine, wherein the free imine function may be substituted with R ¹³ , forms morpholine and thiomorpholine, wherein according to claim 1 one or more H atoms may be replaced by R ¹⁴ , and / or in the manner indicated in claim 1 with one or two identical or different carbo- or heterocyclic groups Cy may be substituted, wherein R ¹³ , R ¹⁴ and Cy have the meaning given in claim 1 or 2. 7. Carbonsäureamid compounds according to claim 6, characterized characterized in that the group

has a meaning according to one of the following Teilformein

wherein one or more H atoms of the heterocycle formed by the group R ¹ R ² N- may be replaced by R ¹⁴ and the ring connected to the heterocycle formed by the group R ¹ R ² N- one or more times on one or more several C atoms with R ²⁰ , in the case of one In addition, phenyl rings can additionally be substituted simply by nitro and wherein R ¹³ , R ¹⁴ , R ²⁰ , R ²¹ and X have the meanings given in claim 1 or 2. 8. Carboxylic acid amide compounds according to one or more of Claims 1 to 7, characterized in that X is a single bond or an unbranched bridge selected from Cι _-6 alkylene, C _2-6 - alkenylene, C2 ₆ alkynylene, Cι-6-alkylenoxy, carbonyl, carbonyl-Cι- ₆ -Alkylene or Cι- ₆ alkylene-amino, wherein the amino group may be substituted with R ⁴ , means wherein one or two C-atoms may be substituted as specified in claim 1 and / or the alkylene bridge with R ¹ as may be connected in claim 1. 9. Carboxylic acid amide compounds according to claim 8, characterized in that X is a single bond, carbonyl or an alkylene bridge selected from methylene, 1, 2-ethylene, 1, 3-propylene and 1, 4- Butylene means in which one or two C atoms independently of one another with a hydroxy, ω-hydroxy-d- _3- alkyl, ω- (-C 3 -alkoxy) -Cι _-3 alkyl and / or C 3 -alkoxy Remainder and / or each with one or two equal or different Cι-4-alkyl radicals may be substituted, and wherein in each case one or more C atoms can be mono- or polysubstituted by F and / or in each case one or two C atoms independently of one another can be substituted simply by Cl or Br. 10. Carboxylic acid amide compounds according to one or more of claims 1 to 9, characterized in that Z is methylene, 1, 2 Ethylene, 1,3-propylene, 1,4-butylene, methylenoxy, 1,2-ethyleneoxy, 1,3-propyleneoxy or 1,4-butyleneoxy, wherein one or two C atoms independently of one another with a hydroxy, _ω-hydroxy-3 Cι- alkyl, O (Cι _-3 alkoxy) -Cι _-3 alkyl and / or alkoxy Cι- ₃ Rest and / or in each case with one or two identical or different Cι. _4- alkyl radicals may be substituted, and in each case one or more C atoms may be mono- or polysubstituted by F and / or in each case one or two C atoms independently of one another can be substituted simply by Cl or Br, and wherein R ^{3 may be} joined to Z including the N atom joined to R ³ to form a heterocyclic group. 11. Carboxylic acid amide compounds according to claim 10, characterized in that Z is selected from the group of bridges -CH ₂ -, -CH ₂ -CH ₂ -, -CH ₂ -CH (CH ₃ ) -, -CH ₂ -C (CH ₃ ) ₂ -, -CH (CH ₃ ) -CH ₂ -, -C (CH ₃ ) ₂ -

or that Z is so connected to R ³ that the group of the sub-formula a meaning selected from 1,3-pyrrolidinylene,

1, 3-piperidinylene, 1, 2,5,6-tetrahydropyridin-1, 3-ylene and 3-hydroxy-1, 3-piperidinylen has. 12. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized in that R ^{3 is} selected from the group methyl, ethyl, n-propyl, iso-propyl, 2-hydroxyethyl, 3-hydroxy-n-propyl and 2-hydroxy 1-methyl-ethyl, wherein in said groups "". - ", 305 334 one, two or three H atoms may be replaced by F, or is selected from the group H, amino-C ₂ - ₃ -alkyl, C ₃ -alkyl-amino-C ₂ -3- alkyl- and di- (Cι _-3 alkyl) amino-C ₂ - alkyl. ₃ 13. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized in that the group Y is selected from the group of bivalent cyclic groups 1, 2-cyclopropylene, 1, 3-cyclobutylene, 1, 3-cyclopentylene, 1, 3rd Cyclopentenylene, 1, 3 and 1, 4-cyclohexylene, 1, 3-phenylene, 1, 4-phenylene, 1, 3 and 1, 4 Cyclohexenylene, 1,4-cyclpheptylene, 1,4-cycloheptenylene, 1,3-pyrrolidinylene, 1, 3-pyrrolinylene, 1, 3-pyrrolylene, 1, 4-piperidinylene, 1,4-tetrahydropyridinylene, 1,4-dihydropyridinylene, 2,4- and 2,5-pyridinylene or 1,4-piperazinylene, wherein the above-mentioned 5-, 6- or 7-membered groups may be connected via two common, adjacent carbon atoms condensed with a phenyl or pyridine ring, where the abovementioned cyclic groups may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , and in the case of a phenyl group may also be additionally substituted simply by nitro, and / or by one or more N atoms with R ²¹ , wherein R ^{1 may be} linked to Y and / or R ³ to Y as defined in claim 1, and R ¹ , R ³ , R ²⁰ and R ^{21 have} the meanings given in claim 1 or 2. 14. Carboxylic acid amide compounds according to claim 13, characterized in that R is connected to Y such that the group of partial formula a meaning selected from the following

subformulae

has.

15. Carboxylic acid amide compounds according to one or more of Claims 1, 2, 3 and 5 to 13, characterized in that the group A is selected from the group of bivalent cyclic groups 1, 2-cyclopropylene, 1, 3-cyclobutylene, 1, 3-cyclopentylene, 1, 3-cyclopentenylene . 1,1,3- and 1,4-cyclohexylene, 1,3- and 1,4-phenylene, 1,3- and 1,4-cyclohexenylene, 1,4-cycloheptylene, 1,4-cycloheptenylene, 1,3-pyrrolidinylene , 1, 3-pyrrolinylene, 1, 3-pyrrolylene, 1, 4-piperidinylene, 1, 4-tetrahydropyridinylene, 1, 4-dihydropyridinylene, 2,4- and 2,5-pyridinylene, 1, 4-piperazinylene, 7 aza-bicyclo [2.2.1] heptane-2,7-diyl and 8-aza-bicyclo [3.2.1] octane-3,8-diyl, wherein the above-mentioned 5-, 6- or 7-membered groups may be connected via two common, adjacent carbon atoms condensed with a phenyl or pyridine ring, and wherein the aforementioned cyclic groups one or more times to one or more C atoms with R ²⁰ , in the case of a phenyl ring also additionally with nitro, and / or may be substituted by one or more N atoms with R ²¹ , and R ²⁰ , R ²¹ and Y have the meanings given in claim 1 or 2. 16. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized in that the group B is selected from the group cyclopropyl, cyclobutyl, cyclopentyl, Cyclopentenyl, cyclohexyl, cyclohexanonyl, cyclohexenyl, phenyl, cycloheptyl, cycloheptenyl, aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, piperidinyl, tetrahydropyridinyl, dihydropyridinyl, pyridinyl, azepanyl, piperazinyl, 1H-pyrazolyl, imidazolyl, triazolyl, tetrazolyl, morpholinyl, thiomorpholinyl , Indolyl, isoindolyl, quinolinyl, Benzoimidazolyl, isoquinolinyl, furanyl and thienyl, wherein the bond to the group W or optionally directly to the group A via a carbon atom of the carbocyclic part or the optionally fused phenyl or pyridine ring or via a N- or C-atom of the heterocyclic part takes place, or B together with the group W connected via a double bond is selected from the group consisting of cyclopentylidene-methyl, cyclohexylidene-methyl and cyclohexanone-4-ylidene-methyl, and wherein the abovementioned cyclic groups may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , in the case of a phenyl group may also be additionally substituted simply by nitro, and / or by one or more N atoms with R ²¹ , and R ²⁰ and R ^{21 have} the meanings given in claim 1 or 2. 17. Carboxylic acid amide compounds according to one or more of claims 1 to 15, characterized in that the group B is selected from the group Ci-β-alkyl, -C ₆ -alkenyl, Ci-β- Aikinyl, C ₃ - ₇ cycloalkyl-Cι alkyl _-3, C _3-7 cycloalkenyl-Cι _-3 alkyl, C ₃ - ₇ - cycloalkyl-d- alkenyl or C 3-7 cycloalkyl ₃ Cι.3-alkynyl-, in which one or more C atoms may be mono- or polysubstituted by halogen and / or simply with hydroxy or cyano and / or cyclic groups mono- or polysubstituted by R ²⁰ , and W is a single bond, -O-, a d-4-alkylene, _C2 -4 alkenylene, _C2 -4 alkynylene, Cι _-4 alkyleneoxy, oxy-Cι- alkylene, C 1-3 alkylene oxy-C1.3- alkylene, imino, N- (Cι _-3 alkyl) -imino-, imino-Cι.4-alkylene-, N- ₍₃ Cι- alkyl) - imino-Cι-4 -Alkylen-, Cι. _4- alkylene-imino or -C-4-alkylene-N- (-C-3-alkyl) - imino group, wherein one or two carbon atoms independently of one another with a hydroxy, ω-hydroxy-C ₃ - alkyl, ω- (Cι- ₃ -alkoxy) -. ₃ -alkyl- and / or -C ₃ -alkoxy radical and / or may be substituted by one or two identical or different Cι- ₄ alkyl radicals, and k is 0 or 1 and R ^{20 has} the meanings given in claim 1 or 2. 18. carboxylic acid amide compounds according to one or more of claims 1 to 15, characterized in that k = 0 and the group A is connected to the group B via a common carbon atom to form a spirocyclic ring system, wherein the group A is a saturated 5- to 7-membered and the group B is a saturated 4- to 7-membered carbo- or heterocyclic group, and wherein the heterocyclic groups each have an N, O or S atom, and wherein a phenyl or pyridine ring may be fused to a 5- to 7-membered group B via two adjacent C atoms, and where the abovementioned cyclic groups may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , in the case of a fused-on phenyl ring additionally also simply by nitro, and / or by one or more N atoms with R ²¹ , R ²⁰ and R ^{21 have} the meanings given in claim 1 or 2. 19. Carboxylic acid amide compounds according to one or more of claims 1 to 15, characterized in that k = 0 and the group B with the group A via two common, adjacent atoms to form a fused, bicyclic saturated, unsaturated or aromatic, 8- is linked to a 12-membered carbo- or heterocyclic ring system, wherein the heterocyclic ring system has one or more identical or different heteroatoms selected from N, O and / or S, and wherein the bicyclic ring system may be monosubstituted or polysubstituted by one or more C atoms with R ²⁰ , in the case of a fused-on phenyl ring also additionally simply with nitro, and / or by one or more N atoms with R ²¹ , where R ²⁰ and R ^{21 have} the meanings given in claim 1 or 2. 20. Carboxylic acid amide compounds according to one or more of claims 1 to 16, characterized in that W is a single bond, -CH ₂ - or -CH =. 1. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized in that Y, A are independently selected from the group of the bivalent cyclic groups 1, 4-phenylene, 1, 4-cyclohexylene, 1, 4-cyclohexenylene, 1, 4-piperidinylene, 1, 2,3,6-tetrahydropyridine 1,4-ylene, 2,5-pyridinylene and 1, 4-piperazinylene, wherein A may also be connected to R ³ according to claim 3, and wherein the aforementioned cyclic groups one or more times to one or more carbon atoms with R ²⁰ , in the case of a phenyl group can also be additionally substituted simply with nitro, and / or to one or more N atoms with R ²¹ , B is phenyl or cyclohexyl, where the groups mentioned may be monosubstituted or polysubstituted by R ²⁰ and / or the phenyl ring additionally may be monosubstituted by nitro, where R ^{20 has} the meanings given in claim 1 or 2, and W is a single bond, -CH ₂ - or -CH =, and Z is -CH ₂ -CH ₂ -, -CH ₂ -CH (CH ₃ ) -, -CH ₂ -C (CH ₃ ) ₂ -, -CH (CH ₃ ) -CH ₂ -, -C (CH ₃ ) ₂ -CH ₂ - or -CH ₂ -Q- or is so connected to R ³ that the group of the sub-formula of the formula I according to claim 1 a meaning

selected from 1,3-pyrrolidinylene and 1,3-piperidinylene and R ³ , R ²⁰ and R ^{21 have} the meanings given in claims 1, 2 and / or 12. 22. Carboxylic acid amide compounds according to one or more of the preceding claims selected from the group of the formulas 1.1 to 1.14

wherein U, V independently of one another C or N, R ²³ , R ²⁴ independently of one another are H, F, methyl, trifluoromethyl, ethyl, iso- Propyl or n-propyl, wherein in the formulas 1.1 to I.6 R ^{24 are} so connected to R ³ that can be the group of the subformula

a meaning selected from 1, 3-pyrrolidinylene and 1, 3 Possesses piperidinylene, and R ²⁵ , R ²⁶ , R ²⁷ are each independently one of the meanings given for R ²⁰ according to claim 1 or 2 or in the case of Phenyl group also simply nitro, where multiple occurring radicals R ²⁵ , R ²⁶ , R ^{27 may have the} same or different meanings, and j is 0, 1, 2, 3 or 4 and m, n are independently 0, 1 or 2 and L ¹ , L ² , L ³ , R \ R ² , R ³ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ²⁰ and X are as defined in claims 1, 2, 5 to 9 and / or 12 have. 23. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized by the formula 1.15

wherein B is selected from the group Cι _-6 alkyl, d _-6 alkenyl, d _-6 - alkynyl, C ₃ - ₇ cycloalkyl-Cι- -alkyl _3, C. _{3 7 cycloalkenyl-d-3} alkyl, C _3-7 cycloalkyl-Cι-3-alkenyl or C _3-7 cycloalkyl-Cι- ₃ alkynyl group, wherein one or more C atoms may be mono- or polysubstituted with halogen and / or simply with hydroxy or cyano and / or cyclic groups may be mono- or polysubstituted with R ²⁰ , and W is a single bond, -O-, a Cι ~ _-4 alkylene, C _2-4 alkenylene, C ₄ alkynylene _2-, Cι- ₄ alkyleneoxy, oxy-C. _{1 4} alkylene, Cι _-3 alkylene oxy-Cι.3 alkylene, imino, N- (Cι _-3 alkyl) -imino-, imino-Cι _-4 - alkylene, N- (Cι- _3- alkyl) -imino-Cι _-4 -alkylene, Cι- alkylene-imino or Cι-4-alkylene-N- (Cι _-3 alkyl) imino group, wherein one or two carbon atoms independently of one another with a hydroxy, ω-hydroxy-d- _3- alkyl, ω- (Cι- ₃ -alkoxy) -Cι- ₃ alkyl and / or -C. ₃ -alkoxy radical and / or may be substituted by one or two identical or different Cι- alkyl radicals, and 0 or 1 means and U, V, R ²³ , R ²⁴ , R ^2δ , R ²⁷ , m, n, L ¹ , L ² , L ³ , R ¹ , R ² , R ³ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ²⁰ and X have the meanings given in claim 22. 24. Carboxylic acid amide compounds according to claim 22 or 23, characterized in that U and V are each C-atom. 25. Carboxylic acid amide compounds according to claim 21, 22, 23 or 24, characterized in that R ¹ , R ^{2 are} independently of one another meaning according to claim 5 and / or 6 and R ^{3 is} a meaning according to claim 12 and X have a meaning according to claim 8 or 9, where the group R ¹ R ² NX- also has a meaning according to Claim may have 7. 26. Carboxylic acid amide compounds according to one or more of claims 21 to 25, characterized in that X is -CH-, -CH (CH ₃ ) - or -C (CH ₃ ) ₂ -. 27. Carboxylic acid amide compounds according to one or more of claims 21 to 26, characterized in that R ²⁵ , R ²⁶ , R ²⁷ independently of one another are F, Cl, Br, I, OH, cyano, methyl, difluoromethyl, trifluoromethyl, ethyl, n-propyl, isopropyl, methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, n-propoxy or isopropoxy , in the case of a substitution of a phenyl group also simply nitro, where multiple occurring radicals R ²⁵ , R ²⁶ , R ^{27 are} identical or different May have meanings, and j is 0, 1 or 2, and m, n are independently 0 or 1. 28. Carboxylic acid amide compounds according to one or more of the preceding claims, characterized in that R ⁶ , R ⁷ , R ⁸ and / or R ^{9 are} independently H, methyl, trifluoromethyl, ethyl, iso-propyl or n-propyl, in the case R ⁶ , R ⁷ also denote F. 29. Carboxylic acid amide compounds according to claim 1 or 2 selected from the group of the formulas (1) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one (2) 3- [2- (4-Pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7-p-tolyl-3 / -quinazolin-4-one (3) 3- [2- (4-Pyrrolidin-1-ylmethylphenyl) ethyl] -7- (4-trifluoromethylphenyl) -3H-quinazolin-4-one (4) 7- (4-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3 / -quinazolin-4-one (5) 7- (3,4-Dichloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethoxy] -3r7'-quinazolin-4-one (6) 7- (4-Fluoro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3-quinazolin-4-one (7) 7- (4-Ethylphenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3- / -quinazolin-4-one (8) 2-Methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7- (4-trifluoromethyl-phenyl) -3H-quinazolin-4-one (9) 2-Methyl-3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -7-p-tolyl-3H-quinazolin-4-one (10) 7- (4-Chloro-phenyl) -2-methyl-3- [2- (4-pyrrolidin-1-yl-phenyl) -ethyl] -3 / - / - quinazolin-4-one (11) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -1H-quinazoline-2,4-dione (12) 7- (4-Chloro-phenyl) -3- {2- [4 - ((S) -2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one (13) 7- (4-Chloro-phenyl) -3- [2- (4-dimethylaminomethyl-phenyl) -ethyl] -3H-quinazolin-4-one (14) 7- (4-Chloro-phenyl) -3- [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one (15) 7- (4-Chloro-phenyl) -3- [2- (4-morpholin-4-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one (16) 7- (4-Chloro-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-benzo [α] [1,2,3] triazine-4 on (17) 5- (4-Fluoro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -isoindole-1,3-dione (18) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (19) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide (20) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-piperidin-1-ylmethyl-phenyl) -ethyl] -amide (21) 4'-Methoxy-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -amide (22) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-diethylaminomethyl-phenyl) -ethyl] -methyl-amide (23) 4- (4-Chloro-phenyl) -cyclohexanecarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (24) 4-Methylphenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (25) 4- (4-Chloro-phenyl) -3,6-dihydro-2H-pyridine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (26) 4- (4-Chloro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (27) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -propyl] -amide (28) 4'-Chloro-biphenyl-4-carboxylic acid (4-pyrrolidin-1-ylmethyl-benzyloxy) -amide (29) 4-Cyclohexyl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (30) 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methoxy-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (31) 7- (4-Chloro-phenyl) -3- {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -3H-quinazolin-4-one (32) 4'-Chloro-biphenyl-4-carboxylic acid {2- [6- (4-methylpiperazin-1-yl) -pyridin-3-yl] -ethyl} -amide (33) 7- (3-Methoxy-phenyl) -3- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -3H-quinazolin-4-one (34) 4- (4-Oxo-cyclohexyl) -Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (35) 4-Cyclohexyl-1-cyclohexylcarboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (36) 4-Benzyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (37) 4-Cyclohexyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (38) 4- (4-Chloro-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (39) 4- (4-Fluoro-phenyl) -piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-yl-methyl-phenyl) -ethyl] -amide (40) 4- (4-Methoxy-phenyl) -piperazine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (41) 4-phenyl-piperidine-1-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (42) (4'-Chlorobiphenyl-4-yl) - [3- (4-pyrrolidin-1-ylmethyl-phenyl) -piperidin-1-yl] -methanone (43) 4'-Chloro-biphenyl-4-carboxylic acid [2-methyl-2- (4-pyrrolidin-1-yl-methyl-1-phenyl) -propyl] -ami d (44) 4'-Chloro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-cyclohexyl) -ethyl] -amide (45) 4-Benzyl- / V- [2- (4-pyrrolidin-1-yl-methyl-phenyl) -ethyl] -benzamide (46) 4- (4-Oxo-cyclohexylidenemethyl) - / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (47) 4'-Chloro-biphenyl-4-carboxylic acid [2- (2-fluoro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (48) 5- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-yl-phenyl) -ethyl] -2,3-dihydro-isoindol-1-one (49) 4-Piperidine-1 -yl- / V- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (50) 7- (4-Chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-benzo [d] [ 1, 2,3] triazin-4-one (51) 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one (52) 7- (4-Chloro-phenyl) -3- {2- [4- (3-aza-spiro [5.5] undec-3-ylmethyl) -phenyl] -ethyl} -3H-benzo [c] [ 1,2,3] triazine-on-4 (53) 7- (4-chloro-phenyl) -3- {2- [4- (4-hydroxy-4-phenyl-piperidin-1-ylmethyl) -phenyl] -ethyl} -3H-quinazolin-4-one (54) 7- (4-Chloro-phenyl) -3- (2- {4- (pyridin-2-yloxy) -piperidin-1-ylmethyl] -phenyl} -ethyl) -3H-quinazolin-4. on (55) 6- (4-Chloro-phenyl) -2- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -H-isoquinolin-1-one (56) 4'-Chlorobiphenyl-4-carboxylic acid [2- (3-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (57) 4'-Chloro-biphenyl-4-carboxylic acid [2- (3-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (58) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-ethyl-piperidin-2-yl) -phenyl] -ethyl} -amide (59) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (4-acetylpiperazin-1-ylmethyl) -phenyl] -ethyl} -amide (60) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (2-azabicyclo [2.2.1] hept-5-en-2-ylmethyl) -phenyl] -ethyl} -amide (61) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (1,3-dihydro-isoindol-2-ylmethyl) -phenyl] -ethyl} -amide (62) 4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(diisopropylamino) -methyl] -phenyl} -ethyl) -amide (63) 4'-Chlorobiphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide (64) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-dimethylaminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide 322/334 (65) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (3-dimethylamino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide (66) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-bromo-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (67) 4-Pent-1-ynyl-Λ / - [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide (68) 4'-Chloro-biphenyl-4-carboxylic acid [2- (6-pyrrolidin-1-ylmethyl-pyridin-3-yl) -ethyl] -amide (69) 4'-Chlorobiphenyl-4-carboxylic acid [2- (1-pyrrolidin-1-yl-indan-5-yl) -ethyl] -amide (70) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-nitro-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (71) 2 ', 4'-Dichlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (72) 4'-Chlorobiphenyl-4-carboxylic acid {2- [4- (3-amino-pyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide (73) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-aminomethylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide (74) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methyl-2,6-diazo-spiro [3,4] oct-6-ylmethyl) -phenyl] -ethyl} -amide (75) 4'-Chloro-biphenyl-4-carboxylic acid [2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -ethyl] -amide (76) 4'-Chlorobiphenyl-4-carboxylic acid [2- (3-ethyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (77) 4'-Bromo-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide (78) 4- (5-Chloro-thiophen-2-yl) -N- [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -benzamide 323/334 (79) 4'-Chlorobiphenyl-4-carboxylic acid [2- (2-methyl-4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (80) 4'-Bromo-3-fluoro-biphenyl-4-carboxylic acid {2- [3-bromo-4- (2,5-dihydro-pyrrol-1-ylmethyl) -phenyl] -ethyl} -amide (81) 4'-Chloro-2-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (82) 4'-Ethyl-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (83) [1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-2-ylmethyl] -carbamic acid tert-butyl ester (84) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpiperidin-1-ylmethyl) -phenyl] -ethyl} -amide (85) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2-methylpyrrolidin-1-ylmethyl) -phenyl] -ethyl} -amide (86) 4'-Chloro-biphenyl-4-carboxylic acid (2- {4 - [(cyclopropylmethyl-amino) -methyl] -phenyl} -ethyl) -amide (87) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (3,4-dihydro-1H-isoquinolin-2-ylmethyl) -phenyl] -ethyl} -amide (88) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4 - {[(2-hydroxy-ethyl) -methyl-amino] -methyl} -phenyl) -ethyl] -amide (89) [1- (4- {2 - [(4'-Chloro-biphenyl-4-carbonyl) -amino] -ethyl} -benzyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester (90) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (2,6-dimethyl-1-piperidin-1-ylmethyl) -phenyl] -ethyl} -amide (91) 4'-Chlorobiphenyl-4-carboxylic acid [2- (4-azetidin-1-ylmethyl-phenyl) -ethyl] -amide (92) 3,4'-dichlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide O 2004/02470 324/334 (93) 4'-Fluorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (94) 4'-Chloro-3-fluoro-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (95) 2'-Fluoro-4'-chlorobiphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (96) 5- (4-Chloro-phenyl) -pyridine-2-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (97) 4'-chloro-biphenyl-4-carboxylic acid {2- [4- (2,5-dihydro-pyrrol-1 ^■ ylmethyl) -phenyl] -ethyl} -amide (98) 4'-Bromo-biphenyl-4-carboxylic acid [2- (4-pyrrolidin-1-ylmethyl-phenyl) -ethyl] -amide (99) 4'-Chloro-biphenyl-4-carboxylic acid {2- [4- (1-pyrrolidin-1-yl-ethyl) -phenyl] -ethyl} -amide 30. Carboxylic acid amide compounds according to claim 29 selected from the group of the formulas (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22 23, 24, 25, 25, 26, 27, 28, 29, 30, 47, and 50 to 99. 31. Process for the preparation of carboxylic acid amide compounds of the formula I.

wherein A, B, W, X, Y, Z, R ¹ , R, R ³ and k are as defined in claims 1 to 28 have meanings indicated in the Case A of a radical R ^{3 which is} not connected to the group A: a) in the case where A is a nitrogen-heterocyclic group linked to the carboxylic acid amide group via a nitrogen atom, which besides the nitrogen atom also contains one or more heteroatoms selected from N, O and S may mean at least one amine compound of formula 1-1

in which R ¹ , R ² , R ³ , X, Y and Z have the meanings given above, with CDT (1,1'-carbonyldi (1,2,4-triazole)) and at least one secondary amine compound of the formula I-2 -W- B I-2 wherein A, B, W and k have the meanings given above and the group A is the sec. Has amine function, is reacted in a solvent or solvent mixture in the presence of at least one base, and b) for the remaining cases at least one carboxylic acid compound of formula I-3

wherein A, B, W and k have the meanings given above, with TBTU (2- (1H-benzotriazol-1-yl) -1,3,3,3-tetramethyluronium 326/334 tetrafluoroborate) and at least one amine compound of the formula 1-1

in which R ¹ , R ² , R ³ , X, Y and Z have the meanings given above, is reacted in a solvent or solvent mixture in the presence of at least one base, and in Case B of a radical R ³ connected to the group A: a) in the case of a group -CR ⁶ R ⁷ - (IIIa) having the group Q, wherein R ⁶ and R ^{7 are} as defined above, an amine compound of formula la.1

in which R ¹ , R ² , X, Y and Z have the meanings indicated, with an o-bromomethyl-benzoic acid derivative of the formula la.2

in which R ⁶ , R ⁷ , W, B and k have the meanings indicated, is reacted, b) in the case of a group -CR ⁶ = CR ⁷ - (IIIb) having the group Q, wherein R ⁶ and R ^{7 are} as defined above, an isoquinolinone derivative of 327/334 Formula lb.2

in which R ⁶ , R ⁷ , W, B and k have the meanings indicated, with an electrophilic compound of the formula Ib.3

in which Y and Z have the meanings indicated and OMs is a suitable leaving group, preferably mesylate, to give an isoquinoline derivative of the formula Ib.4

in which R ⁶ , R ^{7 have} W, B, Y, Z and k have the meanings indicated, and the isoquinoline derivative of the formula Ib.4 is further derivatized by known processes to the compound of the formula I, c) in the case of a group -N = CR ⁸ - (IIIc) having the group Q in which R ^{8 is} as defined above, a phthalazinone derivative of the formula lc.4

in which R ⁸ , W, B and k have the meanings indicated, with an electrophilic compound of the formula Ic.5

in which Y and Z have the meanings indicated and OMs is a leaving group, preferably mesylate, to give a phthalazinone derivative of the formula Ic.6

in which R ⁸ , W, B, Y, Z and k have the meanings indicated, is reacted, and the resulting phthalazinone derivative of formula lc.6 further by known methods to the compound of formula I in which Q is -N = CR ⁸ - (IIIc), is derivatized, d) in the case of a group having the meaning -N = N- (ldd) Q is an o-amino-benzamide derivative of formula ld.1

in which R ¹ , R ² , W, B, X, Y, Z and k have the meanings indicated, in the presence of a suitable nitrite compound and an acid to the compound of formula I, in which Q is -N = N- , is implemented, e) in the case of a -CO-NR ⁹ - (llle) having group Q in which R ^{9 is} as defined above, an o-amino-benzamide derivative of the formula le.1

in which R ¹ , R ² , R ⁹ , W, B, X, Y, Z and k have the meanings indicated, in the presence of CDI (carbonyldiimidazole) to give the compound of formula I in which Q is -CO-NR ⁹ - means, is implemented, f) in the case of a group -CR ⁸ = N- (Ulf) having group Q, in which R ^{8 is} as defined above, an o-amino-benzamide derivative of formula lf.1

o " 330/334 in which R ¹ , R ² , W, B, X, Y, Z and k have the meanings indicated, with a carboxylic acid R ⁸ COOH as defined for R ⁸ and / or a corresponding activated carboxylic acid derivative to the quinazolinone derivative of Formula I, in which Q - CR ⁸ = N-, is reacted, g) in the case of the group Q having the meaning -CO- (IIIg) an isobenzofurandione derivative of the formula Ig.2

in which W, B and k have the meanings indicated, with an amine of the formula Ig.1

in which R ¹ , R ² , X, Y and Z have the meanings indicated, to the compound of formula I, in which Q is -CO-, is reacted. 32. Physiologically acceptable salts of the carboxylic acid amide compounds according to one or more of claims 1 to 30. 33. A composition comprising at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32, optionally together with one or more Physiologically acceptable excipients. 34. A pharmaceutical composition containing at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 in addition to optionally one or more inert carriers and / or diluents. 35. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for influencing the eating behavior of a mammal. 36. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for reducing the body weight and / or preventing an increase in the body weight of a mammal. 37. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for the preparation of a medicament with MCH receptor antagonistic activity. 38. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for the preparation of a medicament, which for the prophylaxis and / or treatment of phenomena and / or diseases caused by MCH or with MCH in another causal relationship, is suitable. 39. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for the preparation of a medicament which is used for the prophylaxis and / or treatment of metabolic disorders and / or eating disorders, in particular of obesity, bulimia , Bulimia nervosa, cachexia, anorexia, anorexia nervosa and hyperphagia, is appropriate. 40. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for the preparation of a medicament which is used for the prophylaxis and / or treatment of obesity-associated diseases and / or disorders, in particular diabetes , especially Type II Diabetes, diabetic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, insulin resistance, pathological glucose tolerance, encephalorrhagia, cardiac insufficiency, cardiovascular diseases, especially arteriosclerosis and hypertension, arthritis and gonitis. 41. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 for the preparation of a medicament which is used for the prophylaxis and / or treatment of hyperiipidemia, cellulitis, fat accumulation, malignant mastocytosis, systemic mastocytosis, emotional disorders, mood disorders, depression, anxiety, sleep disorders, reproductive disorders, sexual disorders, memory disorders, epilepsy, forms of dementia and hormonal disorders. 42. Use of at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to Claim 32 for the preparation of a medicament which is suitable for the prophylaxis and / or treatment of micturition disorders, such as, for example, urinary incontinence, overactive bladder, urinary urgency, nocturia and / or enuresis. 43. A process for the preparation of a medicament according to one or more of claims 33 to 38, characterized in that non-chemical way at least one carboxylic acid amide compound according to one or more of claims 1 to 30 and / or a salt according to claim 32 in one or more inert carriers and / or diluents is incorporated. 44. Medicaments containing a first active ingredient selected from the carboxylic acid amide compounds according to one or more of claims 1 to 30 and / or the salts according to claim 32, as well as a second active ingredient selected from the group consisting of drugs for the treatment of diabetes, drugs for the treatment of diabetic complications, drugs for the treatment of obesity, preferably other than MCH antagonists, drugs for the treatment of hypertension, drugs for the treatment of Hyperiipidemia, including arteriosclerosis, agents for the treatment of arthritis, drugs for the treatment of anxiety and drugs for the treatment of depression, optionally together with one or more inert carriers and / or diluents.