TW200922561A - Azoloarine derivatives, process for their preparation, medicaments comprising these compounds and their use - Google Patents

Abstract

The invention relates to compounds of the formula I in which the radicals R, M, W, X, A, B, D and Y have the indicated meanings, and the physiologically tolerated salts thereof. The compounds are suitable for example for the treatment of the metabolic syndrome, insulin resistance, obesity and diabetes.

Description

200922561 VI. Description of invention:

A tolerable salt. [Prior Art] WO 99/11627 discloses a phenyl benzoate saliva which does not have antibacterial efficacy. WO 03//G32984 discloses a benzo miso as a checkpoint kinase inhibitor. SUMMARY OF THE INVENTION US 2/019965 discloses the promotion of gonadotropin-releasing hormone receptors. The object of the present invention is to provide novel compounds which exhibit medically useful effects. Specific U, the purpose is to find that it is suitable for the treatment of blood and tissue lipid concentration increase, metabolic syndrome, obesity (especially visceral (abdominal) obesity, including prevention of related sequelae), diabetes, insulin resistance, l〇L, A novel compound of HLD and VLDL disorders or cardiovascular disease. Accordingly, the present invention is directed to a compound of formula i:

The definition is: R1-N(R2)-C(=0)-, r5_C(=0)_N(:r1)... R5-S(0)〇.2-N(R1). ^ R1-N( R2)-S(0)〇.2-; 200922561 W Ο, CH2, 〇=〇; X N-R4, Ο, s; A, B, D, Y are independently C(R3) or n, ,, Up to two of the intermediate groups AB, D, and Y are defined as N; R (Cl_Cl6)-alkyl, (Cl-C5)-alkyloxy, (cvcy-alkyl hydrazine, amine group, base 'two ( C2_QH^ylamino, (C1_C6)-alkyl& ylamino, (C1-C6)-homolyl-amino, halogen, thiol, mono-(CrQ)-alkylaminocarbonyl, _(C2_c-alkylaminocarbonyl, (CrQ)-alkoxy, (Ci_c6), burnt base, aryl, trimethyl, trimethylol, (CrC6)-alkyl Sulfhydryl or aminosulfonyl; Ri (C2-c1())-alkyl, wherein alkyl can be dentate, (Crc6)-alkyl, (Ci_c3)-alkyloxy, sea-based, (C1_C6 )-alkylthiol, amine, (crc6)-alkylamino, ^(CrC 2)-alkylamino, _(c6_Cl〇)-aryl, one (C3-C12)-hetero a group, a _(CVCi2)_heterocyclyl or a _(C3_Ci2)_cycloalkyl group, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may be Halogen, (CrC6)-alkyl, (crc3)-alkyloxy, benzyl, (Ci-C6)-alkylthio group, amine group, (Ci-CJ-alkylamino group, di-(C^) -C! 2)-alkylamino group substituted one or more times, (ci-cio)-alkyl group, wherein the alkyl group is -(CVC^aryl, -(C3_C12)-heteroaryl, (G C12) -heteroJ-extension or -(C3 alkyl group substitution, 200922561 wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may optionally be halogen, (CrC6)-alkyl, (crc3)-alkyloxy, hydroxy , (CrQ)-alkylthiol, amine, (CpCA alkylamino, bis-(C^-C)2)-alkylamino substituted one or more times; -(C6-C10)-aryl a group, _(c3_Cl2)_heteroaryl, _(c3_Ci2), a ring group or a -(C3-C12)-cycloalkyl group, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may optionally be halogen, (CrC6)-alkyl, (CVC3)-alkyloxy, thiol, (c^-Q)-alkylthio group, amine group, (crc6)-alkylamino group, bis-(Qc^ alkyl group Substituting an amine group one or more times; R2 hydrogen, (c2_c16)-alkyl, _((VCi〇)_aryl, (Ci_c4)_alkylene-(C6-Ci〇)-aryl; or R1 and R2 Together with the nitrogen atom to which it is attached, it forms a single ring and is saturated. Or a partially unsaturated 4- to 7-membered ring system or a bicyclic saturated or partially unsaturated 8 to 14 membered ring system, wherein each member of the ring system may be 1 to 3 atoms or atoms selected from the group consisting of Group substitution: _CHR4_, _CR4R5_, -(〇R4)-, -NR6-, -C(=〇)...〇_, each, _8〇_ and _3〇2_; R3 hydrogen 2 (Cl_C6)_alkyl, ((VC3)_alkyloxy, hydroxy, (c "c alkyl alkylthio group, amine group, (CrC6)-alkylamino group, bis(c2-c12)-alkyl-moon group, cyano group (CVC6)-alkylcarbonyl, halogen, trifluoromethyl, trifluoromethyloxy, (CrC6)·alkylsulfonyl, aminosulfonyl; hydrogen, (CrCy-alkyl; R5 hydrogen, ( CrCl6)-alkyl, amine group, (c "Ci6)-alkylamino group, two 200922561 -(C2-C!2)-alkylamino group, wherein the alkyl group may be halogen, (crc6)-alkyl, (crc3)-alkyloxy, light base, (Ci_C6)-alkylthiol, amine, (Ci-Cg)-alkylamino, bis-(C2-C12)-alkylamino, -( C6-C10)-aryl, 5 _(C3_Ci2)-heterocyclyl, -(C3-Ci2)L bad group or _(C3-Ci2)_cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclic The base or cycloalkyl group may be optionally halogenated, (Q-C6)-alkane , (CVC3)-alkyloxy, light base, (Ci-C6)-alkylthiol, amine, (Ci-C6)-10 alkylamino, bis-(C2-Ci2)-alkyl Substituting an amine group one or more times; -(C6_Ci〇)-aryl, -(C3-C12)-heteroaryl, -(C3-Ci2)-heterocyclyl or -(c3-c12)-cycloalkyl Wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be 15 13⁄4 , (Ci-Cg)-alkyl, (C1-C3)-alkyloxy, light base, (C!-C6) --- Hyunyl thiol, amine, (C1-C6)-alkylamino, bis-(C2-C12)-''alkylamino substituted one or more times; and physiologically tolerable salt. Preferred compounds of formula I are those wherein 20 M R1-N(R2)-C(=0)-, R5-C(=0)-N(R1)-, R5-S(0)〇.2-N(R1 )-' R1-N(R2)-S(0)〇_2-; WO, C=0; X N-R4 ; A, B, D, Y are independently C(R3) or N, 200922561 Up to two of the groups A, B, D, Y are defined as N; R (Ci-C16)-alkyl, (CrC5)-alkyloxy, alkylthio, amine, (CrC5)-alkylamine , bis-(C2-C8)-alkylamino, (Q-C6)-alkylcarbonylamino, (CrC6)-alkoxycarbonyl-amino, halogen, hydroxy, mono-(crC6)-fired Aminocarbonyl, bis(C2_c8)-alkylaminocarbonyl, (CrC6)-alkoxycarbonyl, (CVC6)-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (CrC6 -alkylsulfonyl or aminosulfonyl; R1 (C2-C)G)-alkyl, wherein the alkyl group may be halogen, (CrC6)-alkyl, (Ci-C3)-alkyloxy, Hydroxy, (Crc6)-alkyl thiol, amine, (Ci_c6)- leumino, bis-(c2-c12)-alkylamino, _(c6_C1())-aryl, -(C3 -C12)-heteroaryl, _(C3_Ci2)_heterocyclyl 4_(c3_Ci2; Mt, substituted, wherein the group, heteroaryl, heterocyclyl or ring group may be halogenated , (rcc6)-alkyl, (crc3)-alkyloxy, per group, (CrC6)-alkylthiol, amine, (crc6)-alkylamino, bis-(qc) 2- Alkylamino group substituted one or more times; (Ci-C1G)-alkyl group, wherein alkyl group is via _(C6-C10)-aryl, -(C3-CI2)-heteroaryl, -(C3-C12 a heterocyclic group or a _(c3_Ci2)_cycloalkyl group in which an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may optionally be halogen, (CrC6)-alkyl, (CrC3)-alkyloxy Substituting, (Crc6)-alkylthiol, amine, 200922561 alkylamino, bis-(C2-C12)-alkylamine substituted one or more times; · R2 ^ oxygen (C2-C16) - an alkyl group, _(C6-C).)-aryl, (CVC4)-extended 5 aryl; -Rl- and H2 together with the nitrogen atom to which they are attached form a monocyclic, saturated or partially Unsaturated 4- to 7-membered ring or bicyclic saturated or partially unsaturated to 14-membered ring system' Members of the ring system can be replaced by 1 to 3 atoms or atomic groups selected from the lower 10 columns :_CHR4-,, :(C==R4)·, _NR6_, -C(=〇)_, _0-, -S-, -SO- and s〇2_; gas (Ci-C6)-shallow base, Calcium-based oxygen, thiol, (c-c) Amine rclylamino, bis-(c-di, yl, fluorenyl, (CVC6)-alkylcarbonyl, dentate, trifluoromethyl, trifluoromethyloxy, (CrC6)-alkylsulfonyl Aminosulfonate R4 hydrogen, ((VC5)-alkyl' 15 (Cl-C! 6)-alkylamino, di-R5 oxime, alkyl, amine-(C2-C12)-alkylamine Base, : calcined base, (CrC3> burning its hepta group, (CrC6)-alkyl sulphur group, scorpion-like amino group, *ylamino group

(CVCl2)-heterocyclic group or tCA cycloalkyl group substituted 3,12), anthracene aryl group, heterofilament, miscellaneous county A Saki kiln, ~C her gas = can; = _ thio group, amine group, (Cl-c6)i-based amino group,: soil lanthanum substituted one or more times; one (2-7 sinyl group 20 200922561 and its physiologically acceptable salt. Particularly preferred compound I is M Rl-N (R2)-C(=〇)- . R5-C(=0)-N(R1)-; W 〇, 〇〇; X NH ; A, B, D, Y CH ; R (crc:16)· Silk, (cvcm-based oxygen, (CrC5 ice-based sulfur, amine group, 10 15 (f rCy-alkylamino group, bis-(C2_C8)-alkylamino group, (Ci_c-alkylcarbonylamino group, (CrC6)) - alkoxycarbonyl-amino, halogen, hydroxy, mono-(CrC6)-alkylaminocarbonyl, diaminocarbonylcarbonyl, (Ci-C6)-alkoxycarbonyl, (CrC6)-alkylcarbonyl, Cyano, trifluoromethyl, difluorodecyloxy, (CrC6)-alkyl yl or amine thiol; R1 (CrC1()H complete, ', among which alkyl--(CVQo) -aryl, -(C3-C12)-heteroaryl, -(C3_C]2)-heterocyclyl or -(c3-c12)-cycloalkyl, wherein aryl, heteroaryl, heterocyclyl or The ring-burning base can be halogenated, (C-C6)- Substituent, (Ci-Cg)-alkyloxy, hydroxy, (cvc6)-alkyl thiol, amine, (crc6)-alkylamino, bis-(C2-C12)-alkylamino Or multiple times; R2 hydrogen, (C2-C16)-alkyl, -(C6_C10)-aryl, (CrQ)-alkyl-(C6-C10)-aryl; R5 hydrogen, (Crc16)-alkyl , Amino, (rcc16)-alkylamino, bis(C2-C12)-alkylamino, 20 200922561 wherein alkyl is halogen, alkyl, (seven alkyloxy, hydroxy, (Cl_C6) -alkyl thiol, amine, (rcc6)-alkylamino, bis-(c2-c12)-alkylamino, _(C6_C10)-aryl, -(C3-C12)-heteroaryl , _(c3_Ci s heterocyclyl or _(c3_Ci2)_cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may be optionally required, (crc6)-alkyl, (q- Co-alkyloxy, a starting group, a (CrC6)-alkylthio group, an amine group, a (crC6)-alkylamino group, a bis(C2-C12)-alkylamine group substituted one or more times; a physiologically tolerable salt. Very particularly preferred compound of formula I is M Rl-NH-C(=〇)-; W ο, c=o ; χ ΝΗ ; A, Β, D, γ CH ; R ( CrC〗 6) _ alkyl, (CrC5)-alkyl oxygen (CVCs)-alkylsulfide, amine group, (CrC5)-alkylamino group, bis(C2_C8)-alkylamino group, (CrC6)-alkylamino group, (CrC6)-alkoxy group Carbonyl-amine, dentate, hydroxyl, mono-(CrC6)-alkylaminocarbonyl, bis(C2_c8)-alkylaminocarbonyl, (CrC6)-alkoxycarbonyl, (Cl_C6)-alkylcarbonyl , cyano, trifluorodecyl di-mercapto based milk, (C 〗 - C6) - burnt stone yellow wine base or amine broth yellow base; Rl (CrC). )-alkyl, wherein the alkyl group is -(C6-C10)-aryl, -(C3-C12)-heteroaryl, -11 - 200922561 -(C^C)2)-heterocyclyl or -(Cs -C! 2)-cycloalkyl substituted, wherein an aryl, heteroaryl, heterocyclyl or cycloalkyl group may optionally be halogen, (Q-C6)-alkyl, (CrC3)-alkyloxy, via , (Ci-C6)-Hyun-based thiol group, amine group, (c!_c) alkylamino group, bis-(C^C!2)-fluorenylamine group substituted once bite; and its physiology A tolerable salt. Also particularly preferred are compounds of formula I wherein M Ri-nh-c(=〇)-; w ο, CO ; x ΝΗ ; A, Β, D, Υ CH ; R (Ci-c) 6-alkyl, (c"C5)-alkyloxy, (Q-C5)-alkylthio, amine, (C1-C5)-alkylamino, bis-(C2_C8)-alkylamino, alkylamine , (Ci-C6)-alkoxy-based amino group, amino group, hydroxyl group, mono-(CVC6)-dishylamino group, bis-(CVCs)-alkylamino group, ( C--C6)-Alkoxy group, (Ci-C6)-alkyl group, cyano group, trifluoromethyl group, trifluoromethyl oxygen, (CrC6)-alkyl group or amine group continued Stiff base; Rl -(CH2)n-(C6-C10)-aryl, -(CEyn-A-Cn)-heteroaryl, -(CH2)n-(C3-C12)-heterocyclyl or -( CH2)n-(C3-CI2)-cycloalkyl, wherein an aryl, heteroaryl, heterocyclyl or cycloalkyl ring may optionally be halogen, (CrC6)-alkyl, (CrC3)-alkyloxy, Hydroxy, (CrC6)-alkyl thiol, amine, (crc6)-alkylamino, bis-(CVC! 2)-alkylamino substituted one or more times; • 12- 200922561 η 2 3, 4; and its physiologically tolerable salt. [Embodiment] - In a specific embodiment, the preferred formula Wherein W is 0. 5 In a particular embodiment, preferred compounds of formula I are those wherein W is ch2. In a particular embodiment, preferred compounds of formula I are those wherein W is c= o In a particular embodiment, the preferred compounds of formula I are those wherein X is N-R4. In a particular embodiment, the preferred compounds of formula I are those wherein X is hydrazine. Preferred compounds of formula I are those wherein X is S. In a particular embodiment, preferred compounds of formula I are those wherein R1 is: R1(C2-C1G)-alkyl, 'wherein alkyl It can be halogen, (CrC6)-alkyl, (CrQ)-alkyl 'oxy, thiol, (Ci-C6)-alkylthio group, amine group, (Ci_C6)-alkylamino group, di-( C2-C12)-alkylamino, -(Cg-Cio)-aryl, 15-(C3-Ci2)-heterocyclyl, _(匸3-(^12)_heterosystem or-(C3- C12)-cycloalkyl substituted, wherein an aryl, heteroaryl, heterocyclic or cycloalkyl group may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, thiol, (Ci-C6 )-alkyl radical, amino group, (Ci_C6)-20 alkyl group, bis-(C2-C12)-alkylamino group substituted one or more times, one In a particular embodiment, preferred compounds of formula I are those wherein R1 is: (Cl_ClQ)-alkyl, wherein alkyl is via -(c6-c10)-aryl, -(c3-c12)-heteroaryl, 13 - 200922561 -(CVC!2)-heterocyclyl or -(C3-C12)_cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (CVC6)- Substituting one or more times of alkyl, (Ci_c3)-yloxy, hydroxy, (CrC6)-alkylthiol, amine, (Ci_c6)-pyringoamine, bis(C2_C12)-alkylamine . In a particular embodiment, the preferred compounds of formula I are those wherein a, b, d, Y are C(R3), C(R3), C(R3), C(R3). In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, ίο Y are NH, C(R3), C(R3), C(R3). In a particular embodiment, the preferred compounds of formula I are those wherein A, B, D, Y are C(R3), NH, C(R3), C(R3). In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, Y are C(R3), C(R3), NH, C(R3). In a particular embodiment, the preferred compounds of formula I are those wherein A, B, D, Y are C(R3), C(R3), C(R3), NH. In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, Y are NH, NH, C(R3), C(R3). In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, 2〇 Y are C(R3), NH, NH, C(R3). In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, Y are C(R3), C(R3), NH, NH. In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, Y are NH, C(R3), NH, C(R3). In a particular embodiment, the preferred compounds of formula I are those wherein A, B, D, Y are NH, C(R3), C(R3), NH. In a particular embodiment, preferred compounds of formula I are those wherein A, B, D, Y are C(R3), NH, C(R3), NH. In a particular embodiment, preferred compounds of formula I are those wherein R3 is hydrogen. In a particular embodiment, preferred compounds of formula I are those wherein R3 is (CrC6)-alkyl, (CrC3)-alkyloxy, thiol, (QQ)-alkylthiol, amine, ( CrC6)-alkylamino, bis-(CVC^2)-alkylamino, cyano, (Ci-C6)-alkyl, halogen, trifluoromethyl, trifluoromethyl, (Ci_c6 An alkylsulfonyl or an aminosulfonyl group. In a particular embodiment, the preferred compounds of formula I are those in which R is he. In a particular embodiment, preferred compounds of formula I are those in which R ^ c is a particular embodiment, and preferred compounds of formula I are those in which a preferred embodiment of the compound of formula I is Wherein 'Cp3° R5-S(〇V2-N(Rl)- or Rl-N(R2)-S(0)〇-2-. ', Μ is a specific embodiment, preferably Formula I The compounds are those having 1 to 4 hetero atomic diheterocyclic rings selected from the group consisting of: N, 0, and S groups may be substituted by (crc16)-alkyl or double bond oxygen. In a specific embodiment, the preferred formula The compound I is # R1-N(R2)-C(=0)-. In a specific embodiment, the preferred compound of formula I is R5-C(=0)-N(R1)'. Use of a compound of formula I: wherein the enthalpy is -15- 20 200922561

The definition is: M R1-N(R2)-C(=0)-, R5-C(=0)-N(R1)-, 5 R5-S(0)〇_2-N(R1)- , R1-N(R2)-S(0)〇_2-, which may comprise from 2 to 4 heterocycles selected from the group consisting of: heteroatoms in the N, oxime, and S groups, wherein the heterocyclic ring may pass (CrC16) -Alkyl or double bond oxygen substitution; W 0, ch2, 〇〇; X N-R4, Ο, S; ίο A, B, D, Y are each independently C(R3) or N, wherein groups A, B Up to two of D, Y are defined as N; R hydrogen, (Q-ce-alkyl, (q-cy-alkyloxy, (crc5)-alkylsulfide, amine, (C1-C5) - anthranyl, bis-(Cz-Cs)-alkylamino, (Ci-Ce)-alkylcarbonylamino, (Crc6)-alkoxycarbonylamino, halogen, hydroxy, 15 mono-( Q-C6)-alkylaminocarbonyl, bis-(C2-C8)-alkylaminocarbonyl, (C!-C6)-alkyloxy group, (Ci-C6)-alkyl group, cyanide , trifluoromethyl, trifluoromethyloxy, (crc6)-alkylsulfonyl or aminosulfonyl; R1(C2-C1G)-alkyl, wherein alkyl can be halogen, (crc6)- Alkyl, (crc3)-alkyl 20 milk, thiol, (Ci-C6)-alkylthione, amine, (Ci_C6)-alkylamino, bis-(c2-c12)-alkylamine Base, -(c 6-c10)-aryl, -16- 200922561 -(C3-C12)-heteroaryl, -(C3-C12)-heterocyclyl or -(c3-c12)-cycloalkyl substituted, wherein aryl, A heteroaryl, heterocyclyl or cycloalkyl group may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, 5 hydroxy, (crc6)-alkyl thiol, amine, (crc6) - an alkylamino group, a bis-(C2_Ci2)-alkylamino group substituted one or more times, (Ci_Ci〇)-homo-based, wherein the alkyl group is -(c6-c10)-aryl, -(c3-c12 )-heteroaryl, 10 _(C3_Ci2)_heterocyclyl or -(C3-Ci2)-cycloalkyl substituted 'wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may be considered to be halogen, (crc6)-alkyl, (crc3)-alkyloxy, thiol, (Ci_C6)-alkylthiol, amine, (Ci_C6)-alkylamino, bis-(C2-Ci2)-alkyl Substituting an amine group once or more than 15 times; -(c6-c10)-aryl, -(c3-c12)-heteroaryl, -(c3-c12)-heterocyclyl or -(C3-C12)-ring Wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may optionally be halogen, (Ci-Q)-alkyl, (CVC3)-alkyloxy, hydroxy, (CrC6)-20 alkyl hydrogen sulfide Base, amine group, (C1-C6)-alkylamino group, di-(C2-Ci2)_ Substituted one or more times; R2 hydrogen, (c2-c16)-alkyl, -(C6-C1())-aryl, (CVC4)-alkyl-(C^-Cio)-aryl Or R1 and R2 together with the nitrogen atom to which they are attached form a monocyclic, saturated or -17-200922561 partially unsaturated 4- to 7-membered ring system or double-ring saturated or partially unsaturated 8- to 14 A ring system in which each member of the ring system can be replaced by 1 to 3 atoms or atomic groups selected from the group consisting of -CHR4-, -CR4R5-, -(C=R4)-, -NR6-, -C( =0) -, -0-, -S-, -SO- and -S02-; 5 R3 hydrogen, (CrC6)-alkyl, (CrC3)-alkyloxy, hydroxy, (CVQ)-alkyl nitrogen Amino group, amine group, (Ci-Cg)-alkylamino group, bis-(C2-C12)-alkylamino group, gas group, (Ci_C6)-alkyl group, halogen, trifluoromethyl group, three mice Mercapto oxygen, (Cl-C6)-alkyl group, amine group, R4 hydrogen, (CrC5)-alkyl; 10 R5 hydrogen, (Ci_Ci6)-dishyl, amine group, (Ci-Ci6 )-alkylamino, bis-(C2-C12)-alkylamino" wherein the alkyl group can be substituted by ii, (crc6)-alkyl, (alkyl milk, light base, (Ci-Cg)- Alkylthio group, amine group, (Ci_C6)-alkylamino group, di-(c2-c12)-alkane Amino, -(c6-c10)-aryl, 15-(C3-Ci2)-heteroaryl, -(C3-Ci2)-heterocyclyl or _(C3-Ci2)-cycloalkyl substituted, wherein aryl The base, heteroaryl, heterocyclic or cycloalkyl group may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, phenanthyl, (Ci-C6)-alkylthione, amine , (Ci-Cg) _ 20 alkylamino group, bis-(C2-C12)··----------(c6-c10)-aryl, -(C3-C12)- Aryl, -(c3-c12)-heterocyclyl or -C3-C12)····························· (Ci_C6)-alkyl, (Ci-C))-alkyloxy, thiol, (c^_c6) alkylthione, amine, (rcc6)-alkylamino, bis(c2_ci2) • a one or more substitutions with a aryl group; and a physiologically pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of obesity. Preferably, a compound of formula I is used, which is defined as M R1-N (R2) )-C(=0)- , R5-C(-0)_N(R1). , R5-S(O)0.2-N(Rl)-, Rl-N(R2)-S(O)0-2 - may comprise from 2 to 4 heteroatoms selected from the group consisting of: heteroatoms in the N, 0, and S groups, wherein the heterocyclic ring may pass through (Cr C16)-alkyl or double bond oxygen substitution; ^ 0, 〇〇; X N-R4 ; A, B, D, Y are each independently C(R3) or N, wherein the groups A, B, D, Y Up to two are defined as ]^[; R hydrogen, (Cl-Cl6)-alkyl, (C1-C5)-alkyloxy, (CVC5)-alkylsulfide, amine, (CrC5)-alkyl Amino, bis(C2_C8)-alkylamino, (CVC6)-alkylamino, (CrC6)-alkoxycarbonylamino, halogen, hydroxy, mono-(CrC6)-alkylamino Carbonyl, bis(C2_C8)-alkylaminocarbonyl, (CrC6)-alkylmercaptocarbonyl, (crc6)-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (Crc6)-alkane Sulfosyl or aminosulfonyl; Rl (C2-C!. a calcinyl group, wherein the alkyl group may be halogen, (CrQ)-alkyl, (crC3)-alkyloxy, hydroxy, (CrC6)-alkyl thiol, amine, (Crc6)·alkylamino , bis-(CVCu)-alkylamino, _(c6-c1())-aryl, •19·200922561 -(C3-C12)-heteroaryl, -(c3-c12)-heterocyclyl or -(c3-c12)-cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, 5 via , (Ci-Cg)-calcinyl thiol' amine group, (Ci_C6)-alkylamino group, bis-(C2-C12)-alkylamino group substituted one or more times; (Cl-ClQ)·&quot An alkyl group via -(c6-c10)-aryl, -(c3-c12)-heteroaryl, 10-(〇3-(^12)-heteronucleonyl or -(C3- C12)-cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, light base, ((^1) -匚6)-alkylthio group, amine group, (Ci_C6)-alkylamino group, di-(C2-Ci2)-alkylamino group substituted once or more than 15 times; R2 hydrogen, (c2-c16) -alkyl, -(C6-C10)-aryl, (CrC4)-alkylene-(C6-C1(3)-aryl; Or R1 and R2 together with the nitrogen atom to which they are attached form a monocyclic, saturated or partially unsaturated 4- to 7-membered ring system or a double-ring saturated or partially unsaturated 8- to 20-membered ring system, Wherein each member of the ring system may be replaced by 1 to 3 atoms or atomic groups selected from the group consisting of -CHR4-, -CR4R5-, -(C=R4)-, -NR6-, -C(=0)- , -Ο-, -S-, -SO- and -so2-; R3 hydrogen, (CrC6)-alkyl, (CrC3)-alkyloxy, hydroxy, (CrC6)-alkyl thiol, amine, (Ci-Cs)-alkylamino, bis-(C2-Ci2)-alkyl-20- 200922561 Amino, cyano, (Ci_C6)-pyrylyl, halogen, trifluoromethyl, trigas Base oxygen, (Ci_C6)-alkyl radical, amine acid group; R4 hydrogen, (CrC5)-alkyl; R5 chlorine, (Ci_Ci6)-alkyl, amine, (Ci_Ci6)-alkylamino , bis 5-(C2-C12)··Huntylamino group, wherein the alkyl group may be halogen, (CrC6)-alkyl, (CrC3)-alkyloxy, hydroxy, (Ci-C6)-alkyl hydrazine Amino group, amine group, (Ci-C6)-alkylamino group, bis-(C2-C12)-alkylamino group, _(C6-Ciq)-aryl group, -(C3-C12)-heteroaryl group, -(匸3-〇12)-hetero group or -(^3-(^12)_cycloalkyl substituted ' 1 Wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may be a desired functional element, (crc6)-alkyl, (Ci-Cs)-alkyloxy, hydroxy, (crc6)-alkyl thiol , an amine group, a (Ci-C6)-alkylamino group, a bis-(C2-Ci2)-alkylamino group substituted one or more times; and a physiologically tolerable salt thereof for use in the manufacture of a therapeutic obesity 15 medicines. It is especially preferred to use a compound of formula I, defined as M R1-N(R2)-C(=0)-, R5-C(=0)-N(R1)-; X ο, c=o ; X N -R4 ; 20 A, B, D, Y are each independently C(R3) or N, wherein at most two of the groups A, B, D, Y are defined as N; R hydrogen, (crc16)-alkyl , (crc5)-alkyloxy, (crc5)-alkylthio, amine, (C1-C5)-alkylamino, bis-(C2-C8)-alkylamino, (Ci_C6)-alkyl Carbonylamino, (rcc6)-alkoxycarbonylamino, halogen, hydroxy, -21 - 200922561 mono-(C1-Q)-alkylaminocarbonyl, bis-(C2-C8)-alkylaminocarbonyl , (Ci-C6)-alkoxycarbonyl, carbonylcarbonyl, cyano, trifluoromethyl, diindenyloxy, (CrC6)-alkyl fluorenyl or amine thiol; Ri (c2-c1Q) - an alkyl group, wherein the alkyl group may be halogen, (crc6)-alkyl, (crc3)-alkyloxy, hydroxy, (CrC6)-alkyl thiol, amine, (Ci_c6)-alkylamino , (CVC! 2)-alkylamino, _(c6-C1())-aryl, -(C3-CI2)-heteroaryl, -(c3-c12)-heterocyclyl or _(c3 -c12)-cycloalkyl substituted, 10 wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (CrC 6)-alkyl, (Q-C3)-alkyloxy, & base, (Ci_C6)-alkylthiol, amine, ((^-(^6)-alkylamino, bis-(() CVCi2)-alkylamino group substituted one or more times; 15 (CrC1G)-alkyl group, wherein the alkyl group is -(C6-C10)-aryl, -(C3-C12)-heteroaryl, -(( VC] 2)-heterocyclyl or _(c3-c12)-cycloalkyl substituted, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may be optionally subjected to a li-, (CrC6)-alkyl group, Crc3)-alkyloxy, benzyl, (CrC6)-alkylthiol, amine, (crc6)-alkylamino, bis-(Cs-C!2)-alkylamine substituted one or more times Secondary; R2 hydrogen, (C2-Ci6)-alkyl, _(C6_Cl〇)-aryl, (Ci_c4)_alkyl-(C6-C10)-aryl; -22- 200922561 or R1 and R2 The attached nitrogen atoms together form a monocyclic 'saturated or partially non- and 4- to 7-membered ring or double-ringed and or partially unsaturated to a 14-membered ring system, wherein each member of the ring system can Replaced by 1 to 3 atoms or atomic groups selected from the following: -CHR4-, _CR4R5_, -(OR4)_, _NR6 ...-C, each, milk and _s〇2_; R3 hydrogen, (crc6)- Burning base, (CrC3)_burning oxygen, warp group, (Ci_c Homothiol, amine, (Ci-c(tetra)ylamino, bis(C2-Cl2)alkyl 10 15 20 amine, cyano, (q-C6)-alkylcarbonyl, halogen, trifluoromethyl , trifluorodecyloxy, (CVC6)-alkylsulfonyl, aminosulfonyl; R4 hydrogen, (crc5)-alkyl R5 nitrogen, (Cl-Cl6)-alkyl, amine, (cvc16 - an alkylamino group, a bis-(C2-C12)-alkylamine group, wherein the alkyl group can be passed through i, (CrC6), alkoxy, thiol, (Q-C6)-hydrogen Mercapto, phenanthrenyl, (Ci_cssylamino, bis-f2-Cl2)-based amine, melon c1G)-aryl, _(c3_Cl2)_heteroaryl, or _(CVCi2)_^&amp Substituted, ^ aryl, heteroaryl, heterocyclic or cycloalkyl may optionally be (tetra), = (tetra), (Crc3)-alkyloxy, minus, (Crc(tetra)yl chloride di, base: (°1 -°6). The hydrazino group, the bis(C2_C12)-alkylamino group are substituted one or more times; the salt of the sputum is used in the manufacture of medicines, and the medicine for the treatment of obesity is defined as =0)-N(Ri); It is particularly preferred to use a compound of formula I, M Rl-N(R2)-C(=0)-, R5_c( -23- 200922561 W ο, c=o ; X N-R4 ; A, B, D, Y CH ; R hydrogen, (crc 16; l·alkyl, (cvcy-alkyloxy, (cvcy-alkylthio, 5 amine, (C1-C5)-alkylamino, bis-(C2-Cg)-alkylamino), Ci_C6) _ burnt-based amino group, (C1-C6)-alkoxyamino group, halogen, arginyl, early _(Ci_C6)-alkylamino group, bis-(C2-C8) - anthranylamino, (QQ)-alkoxycarbonyl, (CrQ)-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (QQ)-alkylsulfonyl or amine Alkyl sulfonyl; ίο Rl (C2-C10)-alkyl group wherein alkyl group can be halogen, (CVC6)-alkyl, (crc3)-alkyloxy, light base, (Ci-C6)-alkyl nitrogen Thio group, amine group, (Ci_C6)-alkylamino group, di-(C2-Ci2)-alkylamino group, -(C6-Ci〇)-aryl group, -(C3_Ci2)_hetero square group, -( C3-Ci2)-heteroyl or -(C3-C12)-cyclic 15 alkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, light-weight, (Ci_C6)-alkylthiol, amine, (Ci_C6)-alkylamino, bis-(C2-C!2)-alkylamino substituted once or 20 times; (Cl_ClQ)-alkyl, wherein the alkyl group is -(c6-c10)-aryl, - (c3-c12)-heteroaryl, _(匸3-(^12)-heterocyclyl or -(C3_Ci2)_cycloalkyl substituted' wherein aryl, heteroaryl, heterocyclyl or cycloalkyl is visible Requires -24- 200922561 to pass halogen, (CrC6)-alkyl, (crc3)-alkyloxy, light-based, (Crc6)-homothiol, amine, alkylamino, di-(C2- Substituting C12)-alkylamine groups one or more times;

At 虱, (C2-CI6)-alkyl, _(C6_Ci〇)_ aryl, (Ci_c4)_alkylene~(C6-C10)-aryl; , and R2 together with the nitrogen atom to which it is attached Forming a single-ring, saturated or 4-injured 4- to 7-membered ring system or a double-ring saturated or partially unsaturated 8_ to W-membered ring system' in which each member of the ring system can be picked up to 3 Substitution from the following atom or atomic group: -CHR4-, -CR4R5-, -(C=R4)-, -NR6-, ~C(=0)-, -〇-, -S-, -SO- and -S02-; R4 hydrogen; R5 hydrogen, (CrC16)-alkyl, amine group, (CrCl alkylamino group, bis-(C2-Ci2)-alkylamino group, wherein the alkyl group can be passed through Crc6)-alkyl, (Cl_C3)-alkyloxy, hydroxy, (CrQ)-alkylthiol, amine, (Ci_C6)-alkylamino, bis-(c2-c12)-alkylamino , _(C6_Ci〇)_aryl, -(C3-C12)-heteroaryl, -(C3-C12)-heterocyclyl or _(c3-c12)-cycloalkyl substituted, wherein aryl, heteroaryl The base, heterocyclic group or cycloalkyl group may optionally be halogen, (CrC6)-alkyl, (Ci-CJ-alkyloxy, hydroxy, (CrQ)-alkylthiol, amine, (Ci_c6)-alkane Substituting one or more times with a aryl group or a bis-(CVC) 2)-alkylamine group -25- 200922561 and its physiologically tolerable salt for the manufacture of a medicament for the treatment of obesity. The present invention relates to a salt form, a racemate, an optical isomer, a rotamer of a compound of formula j. , racemic mixture and pure enantiomers and their diastereomers and mixtures thereof. The mixture is separated by chromatography. The invention includes all possible tautomeric forms of the compounds of formula I. The invention further includes Derivatives of hydrazine compounds, for example, solvates (e.g., hydrates and alcohol adducts), esters, prodrugs, and other physiologically acceptable derivatives of the compounds of formula I, and active metabolites of the compounds of formula I. The invention also includes all crystalline modifications of the hydrazine compound. The alkyl groups in the substituents R, R1, R2 and R3 may be straight or branched. Halogen is fluorine, chlorine, desert or moth, specific δ' Bromo or chloro. The aryl group is a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 10 ring atoms, which may be independently substituted by 1 to 4, preferably 1 or 2, substituents as illustrated. The base is a monocyclic group having 5 to n ring atoms: Less than one aromatic ring has 2 or 3 hetero atoms selected from Ge 2 'the rest is C. The ring alkyl group includes saturation of one or more rings (which consists only of carbon). The unsaturated ring-based heterocyclic group is composed of one or more rings and contains at least one hetero atom. S 4 parts of the unsaturated ring system is a double ring saturated or partially unsaturated and 戸 / or 3 Each member of the group may only include a charcoal atom or contain 1, 1, _ series 'where the ring system

It is selected from the ring heteroatoms of Ν, Ο and S -26- 200922561, and the rest is c. One of the rings in the bicyclic system may be a fused aromatic ring such as benzene. If a group or substituent in a compound of formula I occurs more than once (eg, for example, "R3"), each of them may independently have a defined definition and may be the same or 5 different. Due to physiological tolerance Salts have a higher solubility in water than the original or basic compounds and are therefore particularly suitable for pharmaceutical use. These salts must have physiologically tolerable anions or cations. Suitable physiologically acceptable acid addition salts of the compounds of the invention Salts of inorganic acids, such as hydrochloric acid, 10 hydrobromic acid, phosphoric acid, metaphosphoric acid, nitric acid, amine sulfonic acid and sulfuric acid, and salts of organic acids, such as, for example, acetic acid, benzenesulfonic acid, benzoic acid, Citric acid, ethanesulfonic acid, fumaric acid, gluconic acid, glycolic acid, isethionic acid, lactic acid, lactose-uronic acid, maleic acid, malic acid, methanesulfonic acid, succinic acid, p-toluenesulfonic acid It is especially suitable for medical purposes with tartaric acid. Suitable physiologically tolerable salts are ammonium salts, metal salts (such as sodium and unloading salts) and soil metal salts (such as : magnesium and calcium salts) and 2-amino-2-hydroxyindenyl-1,3-propane a salt of an alcohol (tretin tris-ol; trometamol), diethanolamine, lysine, arginine, biliary, decyl glucosamine or ethylenediamine. The scope of the invention also includes physiologically intolerable An anionic or a cation of a cation of 20 cations which is suitable for the preparation or purification of intermediates of physiologically tolerable salts and/or for non-medical, eg, in vitro use. Another aspect of the invention A prodrug of a compound of the present invention. Such prodrugs can be metabolized in vivo to the compounds of the invention. Such prodrugs are not necessarily active per se. -27- 200922561 The compounds can also be present in a variety of different polymorphic forms, for example: Amorphous and in the form of a day. The scope of the invention includes all polymorphs of the compounds of the invention which form a further aspect of the invention. Hereinafter, "all references to a compound of formula 1" Compound I and its salts, solvates and physiological functional derivatives in (4). (4) The physiological tolerance of the substance and its physiological tolerance. Derived spleen: increased lipid concentration in the night, night and tissues, metabolic syndrome, hypertrophic disease 2 island resistance, LDL, HLD and VLDL disorders or sagittal 1 C 1 metabolism damage, especially the ideal drug for hyperlipidemia. 匕 can also be combined with its n-sex component. 15 20 —, to the desired biological effect of the formula t Many factors and the specific compounds selected by East It, the use of the drug, the mode of administration and the true ro-ro disease. Usually, the daily dose range is 0.1 mg/8/kg of housewife per kilogram of body weight (typically 0,1亳) Gram to 50 mg), for example: 0·1-10 blood test λ λ / day. Rotating agent or capsule may contain, for example, 0.01 to 100 mg, open 3d horse 〇 02 $ itself „ mg ° for prevention or treatment of the above conditions Formula I compounds such that Z is used as the compound 'but preferably forms a pharmaceutical group with an acceptable carrier and does not harm the string carrier. Of course, it must be compatible with the other components of the composition or both. Below the patient's health is acceptable. The carrier can be a solid or a liquid^ and is formulated to be formulated in a single dose with the compound', e.g., a tablet, including other compounds of formula I. The pharmaceutical compositions of the present invention can be prepared by a pharmaceutically acceptable method which essentially comprises a mixed component and a pharmaceutically acceptable carrier and/or excipient. -28- 200922561 The pharmaceutical compositions of the present invention are suitable for oral and oral administration (for example, sublingual). However, the most suitable mode of administration is still the nature and severity of the condition of the disease transferred and the compound of formula I used in each case. Nature depends. Coating formulation 2 and coating sustained release formulations are also included within the scope of the invention. It is preferred to use an acid-resistant and anti-gastric solution. Suitable coatings for anti-gastric juice include cellulose acetate vinegar tartaric acid, polyethylene acetate citrate, propyl methyl cellulose ouic acid and anionic polymers of methacrylic acid and decyl methacrylate. . The pharmaceutical preparation suitable for oral administration may be in separate units, such as sigma, for example, a capsule, a cachet, a film-coated tablet, a buccal tablet or a lozenge, each containing a specified amount of a compound of formula I; in the form of a powder or granule; A solution or suspension contained in an aqueous or non-aqueous liquid; or an oil-in-water or oil-in-water emulsion. As indicated above, such compositions may be prepared according to any suitable pharmaceutical method which comprises the step of contacting the active ingredient with a carrier which may include one or more other compositions. In general, the compositions are prepared by uniformly mixing the active ingredient with a liquid. 15 and / or finely divided solid carrier, and then, if necessary, the product is shaped. Thus, for example, the powder or granule of the compound, if appropriate, may be compressed or formed using one or more other constituents. In the form of a tablet, the compressed tablet is prepared in a free-flowing form such as, for example, a powder or granules, if appropriate, with a binder, a slip agent, an inert diluent and/or 20 or more interfacial activities. The agent/smoothing agent is mixed in a suitable machine. The shaped tablet preparation method can make the powdered compound wet-formed in an appropriate machine using an inert liquid release agent. The pharmaceutical composition suitable for oral (sublingual) administration includes Oral ingot comprising at least one compound of formula I with a flavoring agent (usually a sugar) and gum arabic yellow -29-200922561, and a sugar-coated tablet; Wherein the compound is contained in the inert sugar and the gum arabic. Combination with other pharmaceuticals such as: gelatin and glycerol or sugar cane f compound of the invention can be administered alone or in combination with a variety of other medical orders == right, for example: it can be combined for metabolic disorders Or often with: Guanzhi double active ingredients with beneficial effects. These medicines are 10 1. Drugs that lower blood sugar, anti-diabetic agents 2. Active ingredients for treating dyslipidemia 3. Anti-atherosclerosis drugs 4 Anti-obesity agent 5. Anti-inflammatory active ingredient 6. Active ingredient for treating malignant tumor 7. Antithrombotic active ingredient 15 8. 9. 10 Active ingredient for treating hypertension, treating active ingredients of heart failure, and treating and/or preventing diabetes Or the active ingredient of the complications of diabetes. The active ingredients of other suitable combination products caused by the disease are specifically described as 20. All the reductions in Chapter xi of the R^teListe 2006 in Chapter 12 of the anti-RoteUsW (4) (10) 2: All lipid-lowering agents in Chapter 58 of Rote Liste 2006. It can be combined with the compound of formula I to specifically improve the synergistic effect. Active ingredient ^ human administration The active ingredient is administered to the patient to the patient with a number of active ingredients 2-30 200922561 to synthesize a single pharmaceutical preparation. Most of the activities listed below become US AN and disclosed in US Pharmacopeia, Rockville 2001. USP Dictionary of US AN and International Drug Names. 5 Antidiabetic agents include insulin and insulin derivatives such as, for example:

LantusR (see www.lantus.com) or HMR 1964 or they are described in WO2005005477 (Novo Nordisk), fast acting insulin (see US 6,221,633), inhaled insulin such as, for example, Exubera® or oral insulin such as ' For example: IN_105 (Nobex) or Oral-lynTM (Generex 10 Biotechnology), GLP-1 derivatives such as, for example, Exenatide, Liraglutide or those disclosed in Novo Nordisk A/S 98/08871 or WO2005027978, WO 01/04156 to Zealand or WO 00/34331 by Beaufour-Ipsen, pramlintide acetate (Symlin; Amylin Pharmaceuticals) and a hypoglycemic active ingredient with 15 oral potency. Preferably, the active compound comprises sulfonylureas, biguanides, meglitinides, 20 guanidine diketones, thiazolidinediones, glycosidase inhibitors, hepatic sulphate inhibitors , Glucagon antagonist, 31-200922561 Glucose kinase activator, . Fructose-1,6-bisphosphatase inhibitor, Glucose transporter 4 (GLU4) modulator, glutamine, fructose-6-phosphate Indoleamine-converting enzyme (GFAT) inhibitor, 5 GLP-1 agonist, unloading channel opener such as 'for example: those described in Novo Nordisk A/s, w〇97/26265 and WO 99/03861 Peptidyl peptidase IV (DPP-IV) inhibitor insulin sensitizer 10 / step and inhibitor of liver enzymes that stimulate glucose production and / or hepatic glucose production • glucose absorption, glucose transport and glucose reuptake regulator, Inhibitor of ΙΙβ-HSD1, inhibitor of protein tyrosine phosphatase ΡΤΡΙΒ(ΡΤΡΙΒ), 15 a regulator of sodium-dependent glucose transporter 1 or 2 (SGLT1, SGLT2), a compound that alters lipid metabolism, such as: high resistance Jk lipid active ingredient and anti-lipid active ingredient, reduced Food intake of compounds, the compounds that enhance thermogenesis, 20 PPAR and RXR-control agents, active ingredients acting on the ATP-dependent β- cells of the potassium channels. In a specific embodiment of the invention, the compound of formula I is administered in combination with an HMG_c〇A reductase inhibitor, such as: simvastatin, fluvastatin, pravastatin, lovastatin (1〇vastatin), Teva•32- 200922561 sputum (atorvastatm), cerivastatin, r〇suvastatin or L-659699. In a specific embodiment of the invention, the compound of formula I is combined with cholesterol absorption inhibition, such as ezetimibe, tiqueside, 5 Pamaqueside, FM- VP4 (sitostanol / campesterol anti-spleen sulphate; Forbes Medi-Tech, W02005042692) 'MD-0727 (Microbia Inc., W02005021497) or 5 children in W02002066464 (Kotobuki Pharmaceutical

Co. Ltd.), WO2005062824 (Merck & Co.) or W02005061451 ίο and W02005061452 (AstraZeneca AB) compounds. In a specific embodiment of the present invention, a compound of the formula I is administered in combination with a ΡΡΑΙΙγ·· agonist, such as, for example, rosiglitazone, pigtosa pine (^1 such as 2〇1^), ^-50 Bu 01 262570, 11-483 or €8-011 (rivoglitazone). In a particular embodiment of the invention, the compound of formula I is administered in combination with a PPARa agonist, such as, for example, GW9578, GW-590735, K-111, LY-674, KRP-101 or DRF-10945. In a particular embodiment of the invention, the compound of formula I is administered in combination with a mixed PPARa/gamma-agonist, such as, for example, mulglitazar, tesaglitazar, naveglitazar ), LY_510929, ONO-5129, E-3030, AVE 8042, AVE 8134, AVE 0847 or TRENDS in Pharmacological Sciences described in POT/US 00/11833, PCT/US 00/11490, DE10142734.4 or JP Berger et al. 28(5), 244-251, 2005. -33- 200922561 In a specific embodiment of the invention, a compound of formula I is administered in combination with an ΡΡΑΙΙδ agonist, such as, for example, GW-501516. In a particular embodiment of the invention, the compound of formula I is administered in combination with metaglidasen or indole-2044 or other partial ΡΡΑΙΙγ agonist/antagonist 5 agents. In a particular embodiment of the invention, the compound of formula I is administered in combination with a novolac ethyl ester formulation, such as, for example, fenofibrate, clofibrate or bezafibrate. In a particular embodiment of the invention, the compound of formula I is administered in combination with an MTP inhibitor, such as, for example, implitapide, BMS-201038, R-103757 or as described in WO2005085226. In a particular embodiment of the invention, the compound of formula I is administered in combination with a CETP inhibitor, such as, for example, torcetrapib or JTT-705. In a particular embodiment of the invention, the compound of formula I is administered in combination with a bile acid absorption 15 inhibitor (see, for example, US 6,245,744, US 6221,897 or WOOO/61568), such as, for example, HMR 1741 or their description. On DE 1〇I 2005 033099.1 and DE 10 2005 033100.9. In a particular embodiment of the invention, a compound of formula I is administered in combination with a polymeric bile acid adsorbent, such as, for example, cholestyramine or colesevelam. A particular embodiment of the invention The compounds of formula I are administered in combination with an LDL receptor inducer (see US 6,342,512), such as, for example, HMR1171, HMR1586 or as described in WO2005097738. In a specific embodiment of the invention, the compound of formula I and -34· 200922561

Omacor® ((〇-3 fatty acid; high concentration of eicosapentaenoic acid and ethyl docosahexaenoic acid) is administered in combination. In a specific embodiment of the invention, the compound of formula I and ACAT inhibits the formulation Combination administration, such as 'for example: avasimibe. 5 In a specific embodiment of the invention, a compound of formula I is administered in combination with an antioxidant, such as, for example, OPC-14117, pro; fp. probucol In a specific embodiment of the present invention, a compound of the formula I is administered in combination with a vitamin, such as, for example, vitamin Β6 or vitamin Β12. In a specific embodiment, the compound of the formula I is administered in combination with a lipoprotein lipase modulator, such as, for example, sputum (丨131: 〇邱丨111) (]^0-1886). In an embodiment, a compound of formula I is administered in combination with a citrate citrate lyase inhibitor, such as, for example, SB-204990. In one embodiment of the invention, a compound of formula I is combined with a shark synthesis 15 enzyme inhibitor Dosing, eg, for example: BMS-188494 or instructions on W02005077 907. In a particular embodiment of the invention, the compound of formula I is administered in combination with a lipoprotein antagonist, such as, for example, gemcabene (CI-1027). In one embodiment of the invention, Compound I is administered in combination with HM74A in combination with a 20 agonist, such as, for example, niacin. In a particular embodiment of the invention, a compound of formula I is administered in combination with a lipase inhibitor, such as, for example, Orlistat. Or cetilistat (ATL-962). In a specific embodiment of the invention, a compound of formula I is administered in combination with insulin group -35-200922561. In a particular embodiment of the invention, a compound of formula I is The sulfonylurea combination administration, such as 'tolbutamide, glibenclamide, glipizide or glimepiride. In a specific embodiment of the invention, The compound of formula I is administered in combination with a double vein, such as, for example, metformin. In another embodiment of the invention, a compound of formula I is administered in combination with meglitinide, such as, for example, Rieger. Resistant (repagiini (ie) or Natnay (nateglinide) In a specific embodiment of the invention, a compound of the formula I is administered in combination with a thiazolidine dice, such as, for example, troglitazone, ciglitazone, pitasone (pi〇) Glitaz〇ne), rosiglitazone or Dr. Reddy Research Foundation's WO 97/41097 compound, specifically 5-[[4-[(3,4-dihydro) -3-Methyl-4-oxo-2-quinazolinyloxy)phenyl]methyl]_2,4-thiazolidinone. In a specific embodiment of the invention, a compound of formula I is administered in combination with an alpha-glucosidase inhibitor, such as, for example, migrating migrating or acarbose. In the case, a compound of the formula is administered in combination with an active ingredient acting on an ATP-dependent potassium channel of a cell, such as, for example, 4 inch tolbutamide, glibenclamide, Gypsy ( Glipicide), gHmepiride or repaglinide. In a specific embodiment of the present invention, a compound of the formula I is administered in combination with the above-mentioned compounds, for example, in combination with a sulfonylurea and a diterpene, a -36-200922561 with a urea amide and an acarbus ( Combination of acarbose), combination with repaglinide and diterpene, combination with insulin and sulfonylurea, combination with membrane and a double pulse, combination with membrane and troglitazone , combined with mesin and lovastatin (l〇vastatin) and so on. In a particular embodiment of the invention, the compound of formula I is administered in combination with a glycophosphorylase inhibitor such as, for example, PSN-357 or FR-258900 or as described in WO200308422, WO2004007455, WO2005073229-31 or WO2005067932. In a particular embodiment of the invention, the compound of formula I is administered in combination with a glucagon receptor antagonist, such as, for example, A-770077, NNC-25-2504 or as described in WO2004100875 or WO2005065680. In a specific embodiment of the invention, the compound of formula I is administered in combination with a glucose _ / ligating agent, such as, for example, LY-2121260 (W02004063179), PSN-105, PSN-110, GKA-50 or their description For example: W02004072031, W02004072066 or W02005080360. In a specific embodiment of the invention, the compound is administered in combination with an inhibitor of glucose production, such as, for example, FR-225654. In a specific embodiment of the invention, the compound of formula I is administered in combination with an inhibitor of fructose-1,6-bisphosphatase (FBPase), such as, for example, CS-917. In a specific embodiment of the invention, the compound of formula I is administered in combination with a modulator of glucose transporter 4 (GLUT4), such as, for example, KST-48 (D, 〇. Lee et al., Arzneim.-F0rsch. Drug Res 54(12), 835 (2004)). In a particular embodiment of the invention, the compound of formula I is administered in combination with an inhibitor of glutamine--37-200922561 fructose-6-phosphate guanylamine converting enzyme (GFAT), which is described, for example, in WO2004101528. 5 10 15 20 In a specific embodiment of the invention, a compound of formula I is administered in combination with an inhibitor of dipeptidyl peptidase IV (DPP-IV), such as, for example, vildagliptin (LAF-237) , Sitagliptin (MK-0431), Segdin (5 & parent & 1 1^1) ((3]^8_477118), 〇81^-823093, ?3> 1-9301, SYR -322, SYR-619, TA-6666, TS-021, GRC-8200, GW-825964X or as described in: W02003074500, W02003106456, W0200450658, W02005058901, W02005012312, W02005012308, PCT/EP2005/007821, PCT/EP2005/008005 PCT/EP2005/008002, PC/EP2005/008004 > PCT/EP2005/008283 'DE 10 2005 012874.2 or DE 10 2005 012873.4. In a particular embodiment of the invention, a compound of formula I and ll-β-hydroxysteroid Inhibitors of dehydrogenase-l (llB-HSDl) are administered in combination, for example, as BVT-2733 or as described in, for example, WO200190090-94, WO200343999, WO2004112782, W0200344000, W0200344009, WO2004112779, W02004113310, W02004103980 > W02003104207 , W02004011410, W02004037251, W02004089367, WO200 4112784 > WO 2003065983 'W02003104208, WO2004106294, W02004033427, W02004041264, W02004056744, W02004065351, W02004089380, W02004089470-71, W02004089896, W02005016877 or WO2005097759. -38- 200922561 In a specific embodiment of the invention, the compound i and the protein are cool A combination of an inhibitor of the phosphatase phosphatase (ΡΤΡΙΒ) is described, for example, in W0200119830-31, W0200117516, W02004506446, W02005012295, PCT/EP2005/005311, 5 PCT/EP2005/00532, PCT/EP2005/007151 or DE 10 2004 060542.4. In a specific embodiment of the invention, the compound of formula I is administered in combination with a modulator of sodium-dependent glucose transporter 1 or 2 (SGLT1, SGLT2), such as, for example, KGA-2727, T-1095 and SGL-0010, AVE 2268 and 10 SAR 7226 are described, for example, in WO2004007517, WO200452903, W0200452902 > PCT/EP2005/005959 'W02005085237' JP2004359630 or AL Handlon Expert Opin. Ther. Patents (2005) 15(11), 1531-1540. In a specific embodiment of the invention, the compound of formula I is administered in combination with a modulator of GPR40. In a particular embodiment of the invention, the compound of the formula I is administered in combination with an inhibitor of hormone-sensitive lipase (HSL), as described, for example, in: WO2005073199 ° In a specific embodiment of the invention The compound I is administered in combination with an inhibitor of acetyl-CoA 20 carboxylase (ACC) as described, for example, in W0199946262, WO200372197, WO200372197 or WO2005044814. In a particular embodiment of the invention, the compound of formula I is administered in combination with an inhibitor of a ketol carboxylate kinase (PEPCK) as described in -39-200922561, for example: WO2004074288. In a particular embodiment of the invention, the compound of formula I is administered in combination with an inhibitor of glycogen synthase kinase-3p (GSK-3p) as described, for example, in US2005222220, WO2005085230, PCT/EP2005/005346, 5 W02003078403 > W02004022544 > W02003106410 ' W02005058908 ' US2005038023 ' W02005009997 ' US2005026984 > W02005000836 ' W02004106343 ' EP1460075 , W02004014910 , W02003076442 , W02005087727 or W02004046117 . In a specific embodiment of the invention, a compound of formula I is administered in combination with an inhibitor of protein kinase Cp (PKC β), such as, for example, ruboxistaurin. In a specific embodiment of the invention, the compound of formula I is administered in combination with an endothelin_A receptor antagonist, such as, for example, avosentan (SPP-301). In a specific embodiment of the invention, the compound of the formula I is administered in combination with an inhibitor of "μκΒ kinase" (IKK inhibitor), as described, for example, in W02001000610 'W02001030774 ^ W02004022553 or W02005097129. In a particular embodiment, the compound of formula I is administered in combination with a modulator of a glucocorticoid stature, as described, for example, in WO2005090336. In another embodiment of the invention, a compound of formula 1 is combined with the following: CART modulators (see, Gucun-Amphetamine-regulated 200922561 transcripts affecting energy metabolism, anxiety and gastric emptying in mice) (Cocaine-amphetamine-regulated transcript influences energy mretabolism, anxiety and gastric emptying in mice)" Asakawa , A, et al.: Hormone and Metabolic Research (2001), 33(9), 5 554-558); NPY inhibitors, such as, for example, naphthalene-1-sugar acid {4-[(4-amino hydrazine) Salicyl-2-ylamino)mercapto]-cyclohexylmethyl}decylamine hydrochloride (CGP 71683A); peptide YY3-36 (PYY3-36) or a similar compound, such as, for example, CJC-1682 (with Human serum albumin Cys34 flattened PYY3-36), 1〇CJC-1643 (a derivative of PYY3-36, which is combined with serum albumin in vivo) or as described in WO2005080424; • CB1R (cannabinoid receptor 1) antagonist (e.g., rimonabant, SRI 47778, SLV-319, AVE-1625, MK-0364 or the like, for example: EP 0656354, WO 00/15609, 15 WO2001/64632, WO2001/64633, WO2001 /64634, WO02/076949, W02005080345, W02005080328, W02005080343 'W02005075450 'W02005080357 'W0200170700, W02003026647-48, W0200302776,

W02003040107 ' W02003007887 ' W02003027069 > US 20 6,5 0 9,3 6 7 , WO200132663 , W02003086288 , W02003087037 , W02004048317 , W02004058145 , W02003084930 ' W02003084943 ' W02004058744 > W02004013120 > W02004029204. W02004035566 ' W02004058249 , W02004058255 , W02004058727 , 41 - 200922561 5 W02004069838 US20040214856 W02004096794 US20040266845 W02004000817 W0200500974 > W02005016286 US20050054679 'US20040214837 > W02004096209 > W02005000809' W02004110453 'W02005000820 W02004111033-34, W02005007111' W02005027837, US20040214855,, W02004096763,, W02004099157,, W02004108728,, US20050009870,, W0200411038 -39, , W02005007628, , W02005028456, W02005063761-62 > W02005061509 'W02005077897 > 10 W02006047516, W02006060461, W02006067428 or W02006067443); 15 MC4 agonist (eg 1-amino-1,2,3,4- Tetrahydro-naphthalene-2-carboxylic acid [2-(3a-phenylhydrazino-2-methyl-3-yloxy-2,3,3a,4,6,7-hexahydro-pyrazolo[4, 3-c] acridine-5-yl)-1-(4-chlorobenzene )-2-oxoethyl]-decylamine; (WO 01/91752)) or LB53280, LB53279, LB53278 or THIQ, MB243, RY764, CHIR-785, PT-141 or their descriptions are: W02005060985, W02005009950 , W02004087159, W02004078717, W02004078716, W02004024720, US20050124652, W02005051391, WO2004112793, 20 WOUS20050222014, US20050176728, US20050164914, US20050124636, US20050130988, US20040167201, W02004005324, W02004037797, W02005042516, W02005040109, W02005030797, US20040224901, W0200501921, W0200509184, W02005000339, -42- 200922561 EP1460069 'W02005047253 'W02005047251 > EP1538159 > W02004072076 or W02004072077; orexin receptor antagonist (for example: 1-(2-mercaptobenzox-6-yl)-3-[1,5] Naphthyridin-4-ylurea hydrochloride (SB-334867-A) or as described, for example, in WO200196302, WO200185693, WO2004085403 or WO2005075458); histamine H3 receptor agonist (eg 3-cyclohexyl-l) -(4,4-Dimethyl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl)-propan-1-one oxalate (WO 00/63208 ) or their description on W0200064884, W02005082893); ίο 15

CRF antagonist (for example: [2-methyl-9-(2,4,6-tridecylphenyl)-9Η-1,3,9-triazaindole-4-yl]dipropylamine ( WO 00/66585)); CRF BP antagonists (eg, urocortin); urocortin agonists; β3 agonists (eg, 1-(4-chloro-3-) Methanesulfonyl decyl phenyl)-2-[2-(2,3-dimercapto-1 Η-σ π-tox-6-yloxy)ethylamino]ethanol hydrochloride (WO 01/83451) )); MSH (melanocyte stimulating hormone) agonist; MCH (melanin-concentrating hormone) receptor antagonist (eg, for example: ΝΒΙ-845, Α-76 Α-665798, Α-798, ATC-0175, Τ -226296, 20 Τ-71, GW-803430 or their descriptions are: W02005085200 ' W02004012648 ' W02005070898 ' W02003033476 , W02005019240 > W02003015769 , W02005070925 ' W02002006245 , WO2003/15769 > W02004011438 , W02004072025 , W02004039780 , W02002002744 , -43 - 200922561 W02003004027 or FR2868780); CCK-A agonist (eg, for example: {2-[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)) _thiazole-2-aminoamine]-5,7-dimercapto-l-yl}acetic acid trifluoro Acetate (WO 99/15525), SR-146131 (WO 5 0244150) or SSR-125180); serotonin reuptake inhibitors (eg dexfenfluramine); mixed A-clearin-induced and adrenal gland a stimulating compound (for example: WO 00/71549); a 5HT receptor agonist, for example: 1-(3-ethylbenzofuran-7-yl) piperidine oxalate (WO 01/09111); 5-HT2C receptor agonists (eg, APD-356, BVT-933 or those described in WO200077010, W020077001-02, WO2005019180, WO2003064423, WO200242304 or WO2005082859); 15 5-HT6 receptor antagonists, eg, They are described, for example, in W02005058858; scorpion receptor agonist (BRS-3 agonist); sorghum curcumin receptor antagonist; growth hormone (eg human growth hormone or AOD-9604) 20; a compound that releases growth hormone (6-benzoquinone-1-(2-diisopropylaminoethylcarbamic acid)-3,4-dihydro-1H-isoindolene-2-tagacid Third Dingzhi (WO 01/85695)); a growth hormone secretagogue receptor antagonist (growth chemokine antagonist), such as, for example, A-778193 or their description in WO2005030734; -44·2 00922561 TRH agonist (see for example: EP 0 462 884); decoupled protein 2 or 3 modulator; obesity protein agonist (see for example: Lee, Daniel W.; Leinung, Matthew C.; Rozhavskaya-Arena, Marina ; Grasso, Patricia. 55 5 Leptin agonists as a potential approach to the treatment of obesity. Drugs of the Future (2001), 26(9), 873-881) DA agonist (bromocriptine, Doprexin); lipase/amylase inhibitor (described in, for example, WO 00/40569); ίο dimercaptoglycerol 0-thiol conversion Inhibitors of the enzyme (DGAT) are described, for example, in US 2004/A0224997, WO2004094618, W020005849, WO2005044250, WO2005072740, JP2005206492 or WO2005013907; fatty acid synthase (FAS) inhibitors such as, for example, C75 or their descriptions 15 to WO2004005277; Oxyntomodulin; oleoyl-estrone; or scorpion gonadotropin receptor agonist such as, for example, ΚΒ-2Π5 or as described in WO20058279, WO200172692, WO200194293, 20 W02003084915, W02004018421 or W020050 92316. In a particular embodiment of the invention, the other active ingredient is an obese protein; see for example: 'Perspectives in the therapeutic use of leptin", Salvador, Javier; Gomez-Ambrosi, Javier; Fruhbeck, Gema, Expert Opinion on •45· 200922561

Pharmacotherapy (2001), 2 (10), 1615-1622. In one embodiment of the invention, the other active ingredient is dextroamphetamine or amphetamine. In a particular embodiment of the invention, the other active ingredient is fenfluramine or dexfenfluramine. In another embodiment of the invention, the other active ingredient is sibutramine. In another embodiment of the invention, the other active ingredient is mazindol or phentermine. In a particular embodiment of the invention, the compound of formula I is administered with a bulking agent, preferably with an insoluble bulking agent (see for example: croton gum/Caromax® (Zunft HJ; et al. Carob pulp preparation for treatment of hypercholesterolemia, ADVANCES IN THERAPY (2001 15 Sep-Oct), 18(5), 230-6). Caromax is a kind from Nutrinova.

Nutrition Specialties & Food Ingredients GmbH (Industriepark H6chst, 65926 Frankfurt/Main) is a product containing locust bean gum. The combination with Caromax® can form the same formulation, or the compound of formula I can be administered separately with Caromax®. Caromax® can also be used as a food product, such as, for example, in baked goods or breakfast cereal bars. It is to be understood that a suitable combination of a compound according to the invention with one or more of the abovementioned compounds and one or more other pharmaceutically active substances as desired is included within the scope of the invention. -46- 200922561

Liver

47- 200922561

HO

OH

ATL-962

HO

FR-258900

OH

Ο NNC-25-2504

-48- 200922561

ο NIS.

-49- 5 200922561

ATC-0175

GW-803430 -50- 200922561

The following examples illustrate the invention in more detail, but do not limit the products and specific examples illustrated in the examples which follow. Table 1: -51 - 200922561

I Instance RWXABDYM [bonding position on atom] 2 Η 0 ΝΗ CH CH CH CH CONHCH2CH2CH2-(pyridine-3-yl); [B] 3 Η 0 ΝΗ CH CH CH CH CONHCH2CH2CH2-stupid; [B] 4 Η 0 ΝΗ CH CH CH CH CONHCH2CH2-phenyl; [B] 5 Η 0 ΝΗ CH CH CH CH CONHCH2CH2CH(CH3)2; [B] 6 Η 0 ΝΗ CH CH CH CH CONHCH2CH2-cyclopropyl; [B] 7 Η 0 ΝΗ CH CH CH CH CONHCH2-cyclopropyl; [B] 8 Η 0 ΝΗ CH CH CH CH CONHCH2-(5-chlorothiophen-2-yl); [B] 9 Η 0 ΝΗ CH CH CH CH CONHCH2-( Thiazol-2-yl); [B] 10 Η 0 ΝΗ CH CH CH CH CONHCH2CH2CH2-O-CH2CH2CH2CH3; [B] 12 2-C1 0 ΝΗ CH CH CH CH CONHCH2CH2-phenyl; [B] 13 2-C1 0 ΝΗ CH CH CH CH CONHCH2CH2CH(CH3)2; [B] 14 2-C1 0 ΝΗ CH CH CH CH CONHCH2CH2-cyclopropyl; [B] 15 2-C1 0 ΝΗ CH CH CH CH CONHCH2-(5-chlorothiophene -2-yl);[B] 16 2-C1 0 ΝΗ CH CH CH CH CONHCHr(thiazol-2-yl); [B] 18 2-CF3 0 ΝΗ CH CH CH CH CONHCH2-(5-chlorothiophene-2 -Base); [D] 19 2-CF3 CO ΝΗ CH CH CH CH CONHCHr (thiazol-2-yl); [B] 20 2-CF3 CO ΝΗ CH CH CH CH CONHCH2CH(CH3)2; [B] 22 2 -CF3 0 S CH CH CH CH conhch2ch(ch3)2; [D] •52- 200922561 Example RWXABDYM [Atomic bonding position J 23 2-CF3 0 NH CH CH CH CH CONHCH2CH2-cyclopropyl; [D] 24 2- CF3 0 NH CH CH CH CH CONHCH2CH(CH3)2; [D] 25 2-CF3 0 NH CH CH ^ CH CH CONHCH2-(thiazol-2-yl); [D] 26 2-CF3 0 NH CH CH CH CH CONHCH2CH2CH2-styl; [D] 27 2-CF3 CO NH CH CH CH CH CONHCH2-(5-athiophen-2-yl); [D] 28 2-CF3 CO NH CH CH CH CONHCH2-(thiazole-2 -Base); [B] The activity of the compound of the formula i of the present invention is examined by microsomal enzymes according to the following analysis system: The liver of a Wistar rat that has been fed a high-carbohydrate, low-fat diet (for inducing SCD1 expression) The Potter tissue homogenizer was ground and differentially centrifuged in a buffer containing 250 mM sucrose and 5 mM HEPES (pH 7.0). The portion of the resuspended microsome is stored under "(9). In the thin layer chromatography, stearic acid _c〇A desaturase activity was determined using stearic acid labeled 1-14C. Briefly, each compound of the invention (containing a final concentration of 1% [v/v] in dmso) and 15 pg of rat liver microsomes in 200 μM assay buffer (6 mM MgCl2, 250 mM Yan sugar) , 150 mM KC1, 40 mM NaF, l mM Na2HP04 (pH 7.4), l.3mMATP, h5mM glutathione, 60 μΜ C〇A, 0.33 mM nicotinic amide and 0.94 mM NADH) I〇min was incubated at room temperature. Add ο” stearic acid (55 mCi/mmol) and mix at 37. (: culture for 1 h. Take the labeled fatty acid via 2.5 M KOH/MeOH: H2〇(4:1) at 65. (: hydrolysis for 4 h, protonation with 280 μΐ formic acid, 5 μμ1 Alkane extraction. Take -53- 200922561 TLC analysis plate private brain AgN〇3 t, add time & (four) plus 15 〇 to burn the phase to the analysis plate, TLC plate in the buffer two, imitation. methanol. acetic acid: water [ 9G : 8 : ! ·· 〇.8]) and dry ^ in the Phospholmager instrument readings, quantitative scm activity. The board in this related art can modify the conditions of this analysis under the condition of hard soil _ ^ money (four) miscellaneous In the analysis of K.2, it is expressed as a percentage inhibition of the activity of St SCD1 as an inhibitor of SCD1. The injection is shown in Table 2: Biological activity of a specific compound

•54· 200922561

Metabolism (2005), 2(4), 251-261 and Warensjoe et al., Diabetologia (2005), 48(10), 1999-2005). Since the compounds of formula I inhibit SCD activity, they are also useful in the treatment or prevention of other s c D -mediated diseases or SCD-mediated disorders in mammals, preferably humans. 10 15 20 The compounds of the invention are particularly suitable for the treatment and/or prevention of 1.1,... 2. 3. 4. Obesity, especially visceral (abdominal) obesity - fatty acid metabolism lesions and glucose utilization lesions - which involve insulin resistance The lesion. Diabetes, especially type 2 diabetes, including prevention of this aspect, especially refers to fork retreats • to blood sugar, - improve insulin resistance, - improve glucose tolerance, _ protect whole island beta cells, - prevent macrovascular and microvascular disease . ^lipid abnormalities and Wei fine, such as, for example, Misaki arterial heart disease, cerebrovascular disease, etc., especially one or more of the following characteristics of: 〜, 峨: - not limited to: - high plasma triglyceride Ester concentration, high postprandial plasma low HDL cholesterol concentration I oil ester concentration • low ΑροΑ lipoprotein concentration - high LDL cholesterol concentration - low fee LDL cholesterol particles • *55- 200922561 - sorghum ροβ lipoprotein concentration - ancient (four) σ know number ( For example: ratio 18 : 1 /18 : 0η_9, 〇 or 18. 1η-9+ 16 : 1η_7/16 : 〇 fatty acid) 5- · i / 1 〇: =: Γα: high (four) glycerol slightly, or low chaos) - excessive coagulation jk 10 - uric acid ash - microalbuminuria - thrombosis, hypercoagulability and procoagulant disorders (arteries and veins) - hypertension 15 - heart failure such as, but not limited to: myocardial infarction, Hypertensive heart disease or myocardial lesions 6. Liver disease and related disorders - fatty liver 20 - liver steatosis - non-alcoholic hepatitis - non-alcoholic steatohepatitis (N ASH) - alcoholic hepatitis acute fatty liver - pregnancy fatty liver - Drug-induced hepatitis - iron storage disease • 56- 200922561 - Liver fibrosis-cirrhosis-liver tumors--viral hepatitis5 7. Skin diseases and conditions and their diseases and conditions related to polyunsaturated fatty acids-Eczema-acne-dryness10-Formation or prevention of crab foot swelling - Other diseases related to mucosal fatty acid composition' 8. Primary high blood triglyceride or subsequent follow-up of the following diseases • High blood triacetin - familial reticulosis 15 - lipoprotein lipid Enzyme deficiency - hyperlipoproteinemia - apolipoprotein deficiency (eg: apoCII or apoE deficiency) 9. Diseases or conditions associated with neoplastic cell proliferation - benign or malignant tumors 20 - cancer - newborn 赘Tumor-metastasis-cancer lesions 10_ Diseases or conditions associated with neurological, psychological or immune diseases or conditions-57-200922561 π. Other diseases or conditions that may involve, for example, inflammatory responses, cell differentiation and/or other SCD-mediated aspects : - atherosclerosis such as: (but not limited to): coronary arteriosclerosis, including angina or myocardial infarction, stroke, acute stroke, and 5 temporary extinct jk stroke (TIA) - peripheral obstructive disease - vascular surgery Posterior restenosis or reocclusion - chronic inflammatory bowel disease such as, for example, Crohn's disease and ulcerative colitis 1 - pancreatitis - sinusitis - other inflammations - nephropathy, renal nephropathy - Adipocytoma 15 - lipoma, such as, for example, liposarcoma - solid tumors and neoplastic tumors - such as (but not limited to): gastrointestinal cancer, liver cancer, bile duct and pancreatic cancer, endocrine tumor , lung cancer, kidney and urinary tract cancer, genital tract cancer, prostate cancer, etc. 20 - acute and chronic spinal hyperplasia and lymphoma - neovascularization - neurodegenerative lesions - Alzheimer's disease - Multiple sclerosis-58 - 200922561 - Parkinson's disease - erythema - squamous skin diseases such as: Cognac - Acne vulgaris _ - Other skin lesions and skin diseases regulated by PPAR 5 - Wet therapy and neurodermatitis - dermatitis such as: sebum leakage dermatitis or photodermatitis - keratitis and keratosis such as: sebum leakage keratosis, senile keratosis, actinic keratosis, photo-induced keratosis Or follicular keratosis 1〇-kelsy and prevention Tumor-weakness, including wetness or sexually transmitted diseases, wet-hepatic human papillomavirus (HPV) infection, such as: sexually transmitted diseases, nipples, tumors, viral fatigue, such as: infectious soft fatigue, mucosal leukoplakia 15 - mound Therapeutic skin diseases such as, for example, lichen planus - skin cancer such as, for example, basal cell carcinoma, melanoma or cutaneous T-cell lymphoma - local benign epidermal tumors such as, for example, keratoderma, epidermal cancer 20 - Hypertension-X Syndrome - Polycystic ovary syndrome (PCOS) - Asthma-fibrocyst - 59- 200922561 • Osteoarthritis., Lupus erythematosus (LE) or inflammatory rheumatoid lesions such as rheumatoid joints Inflammation _ vasculitis 5 - weak (malignant disease) gout - anemia / reperfusion syndrome _ acute dyspnea syndrome (ARDS) - viral diseases and infections 10 - fat loss of the body and body fat dystrophy 'can also Treatment of adverse drug reactions (eg, after taking drugs for treatment of HIV or cancer) - Muscle lesions and fatty muscle lesions (eg, carnitine palmitoyl-transferase I or II deficiency) Animal management and human muscle formation and Lean body or muscle 15 into the shape. Process The compounds of the formula I according to the invention are prepared according to methods known in the literature (for example: McClure, Kelly J.; Huang, Liming; Arienti, Kristen L.; Axe, Frank U.; Brunmark, Anders; Blevitt, Jon; Guy 20 Breitenbucher, J.; Bioorganic & Medicinal Chemistry Letters (2006), 16(7), 1924-1928; Arienti, Kristen L.; Brunmark, Anders 1 Axe, Frank U.; McClure, Kelly; Lee, Alice; Blevitt, Jon; Neff, Danielle K.; Huang, Liming; Crawford, Shelby; Pandit, Chennagiri R., Karlsson, Lars; 200922561

Breitenbucher, J. Guy, Journal of Medicinal Chemistry (2005), 48(6), 1873-1885), and can be prepared according to the following reaction sequence, wherein the group is as defined above.

(8) (ΠΙ) (I) The compound used as the starting material can be obtained from the product or can be prepared according to methods known in the literature; for example, the 4-phenoxy-substituted benzoquinone can be prepared from an appropriately substituted phenol. Reaction with 4-fluoro- or 4-chlorobenzaldehyde in the presence of a base (eg: Pfefferkom, Jeffrey A.; Greene, Meredith L.; Nugent, Richard A.; Gross, Rebecca J.; Mitchell, Mark A.; Finzel, Barry C. ; Harris, Melissa S. ; Wells, Peter A. ; Shelly, John A. ; Anstadt, Robert A. ; Kilkuskie, Robert E. ; Kopta. Laurice A. ; Schwende, Francis J Bioorganic & Medicinal — Chemistry Letters (2005), 15(10), 2481-2486). On the other hand, these compounds can also be reacted with a 4-bromophenol and a halogenated aromatic compound, and then converted into a corresponding thiophene.

-61 - 20 200922561 Diamine hydrazide can be prepared according to the method described by P. Chand et al., Bioorganic & Medicinal Chemistry Letters (2005), 13(7), 2665-2678. The substituted 4-benzylbenzoquinone can be prepared by a method similar to that of Langle, Sandrine; Abarbri Mohamed; Duchene, Alain, 5 Tetrahedron Letters (2003), 44 (52) 9255-9258. The benzofurfural substituted with benzhydryl group can be obtained by oxidation of the corresponding alcohol. This method is described in Kashiwagi, Yoshitomo; Ikezoe, Hiroshi; Ono, Tetsuya. Synlett (2006), (1), 69-72; Smith, Amos B., Ill; Rucker, Paul V.; Brouard, Ignacio; Freeze, B Scott; Xia, ίο Shujun; Horwitz, Susan Band. Organic Letters (2005), 7(23), 5199-5202.

Another method uses the Friedel-Crafts deuteration method followed by side chain halogenation and hydrolysis: Nakatani, Kazuhiko; Dohno, Chikara; Saito, Isao. Journal of Organic Chemistry (1999), 64 (18), 6901-6904. 62- 200922561

If the acid is released during these reactions, it is advisable to add an assay (eg tl bite, triethylamine, sodium hydroxide solution or alkali metal carbonate) to increase the reaction rate. The reaction can be carried out in a wide temperature range. It has been proven that it is appropriate. 〇 Operate between the boiling points of the solvent used. Examples of solvents used are methylene chloride, THF, DMF, toluene, ethyl acetate, n-heptane, dioxane, diethyl ether or pyridine. It has also been found to be suitable for the use of strong bases under anhydrous conditions, such as: lithium hydride, sodium hydride or potassium butoxide, in the aprotic solvent (eg THF or DMF) in the form of the compounds of the formula I in a manner known per se. (eg extraction, crystallization or chromatography) isolated and purified from the reaction mixture. The following examples are intended to illustrate the invention, but are not intended to be limiting. These compounds can be identified by mass spectrometry. Example 1: 2-(4-phenoxyphenyl)_311_benzimidazole-5-carboxylic acid ethyl ester dropwise addition of 50 ml of water-containing solution containing sodium metabisulfite (10.55 g, M.49 mmol) to nitrogen The next $ oxy acyl acid: (ι. 〇g, 55.49 mmol) -63 ** 200922561 250 ml ethanol solution. The separated thick precipitate was diluted in 50 ml of ethanol, stirred at room temperature for 4 h, and stored in a refrigerator overnight. The precipitate was filtered off with suction, washed with ethanol and dried. The intermediate was taken up in 100 ml of DMF, and ethyl 3,4-diaminobenzoate (10.0 g, 55.49 mmol) was added and stirred at 5130 ° C for 4 h. DMF was removed by vacuum distillation, the residue was combined with water and ethyl acetate. The organic phase was separated, washed with water, dried and concentrated. The resulting crude product (18.3 g) was further reacted. Example 2: ίο 2-(4-phenoxyphenyl)-3H-benzimidazole-5-(3-acridin-3-ylpropyl)carboxamide 2a: 2-(4-phenoxybenzene Base-3H-benzimidazole-5-carboxylic acid - Ethyl 2-(4-phenoxyphenyl)-3H-benzimidazole-5-carboxylate (2.0 g, 5.58 mmol) was dissolved in 10 mL THF. After adding a 30 ml aqueous solution containing hydrazine hydroxide hydrate (1.64 g, 15 39.08 mmol), it was stirred at room temperature for 22 h. The THF was distilled off and the aqueous phase was extracted with ethyl acetate. The aqueous phase was further acidified with 4N hydrochloric acid, and the product was filtered off with suction, washed with water and dried. Yield: 1.64 g (89%), M+H+: 331.09. 2b : 2-(4-phenoxyphenyl)-3H-benzimidazole-5-(3-u-bipyridin-3-ylpropanyl 20-yl)carbenamide added triethylamine (0.15 ml, 1· 078 mmol) and HATU (0.246 mg, 0.647 mmol) to 2-(4-phenoxyphenyl)-3H-benzene. Sodium-5-formic acid (178 mg, 0.539 mmol) and 3-σ ratio -3-propylpropylamine (80.09 mg, 0.594 mmol) in 10 ml of DMF were stirred at room temperature for 6 h. The reaction mixture was -64 - 200922561, and the residue was combined with water and ethyl acetate. The organic phase was separated, washed with water, dried and concentrated. The crude product obtained was purified by preparative HPLC (RP18, EtOAc / EtOAc. Yield: 217 mg (90%), M+H+: 449.29. Example 3: 2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-phenylpropyl)carboxamide from 2-(4-phenoxyphenyl)-3H-benzimidazole- 5-carboxylic acid was reacted with 3-phenylpropylamine analogously to the method of Example 2b. Yield · 97 mg (40%), M+H+ : 448.28. Example 4: 2-(4-Phenoxyphenyl)-3H-benzimidazole-5-phenethylguanamine from 2-(4-.Phenoxyphenyl)-3H-benzimidazole_5-carboxylic acid The reaction with phenethylamine is similar to the method of Example 2b. Yield: 70 mg (30%), M+H+: 434.26. Example 5: 2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-decylbutyl)decylamine from 2-(4-phenyloxyphenyl)·3Η-benzoimidazole The citric acid was reacted with 3-mercaptobutylamine similarly to the method of Example 2b. Yield: 58 mg (27%), Μ+Η+: 400.27. Example 6: 2-(4-Phenoxyphenyl)-3H-benzimidazole_5-(2-cyclopropylethyl)phosphonium-65- 200922561 Amine from 2-(4-phenoxyphenyl)- 3H-benzimidazole-5-carboxylic acid was reacted with 2-cyclopropylethylamine hydrochloride analogously to the method of Example 2b. Yield: 26 mg (12%) M+H+ : 398.16. Example 7: 2-(4-Phenoxyphenyl)-3H-benzimidazole-5-cyclopropylmethylformamide from 2-(4-phenoxyphenyl)-3H-benzimidazole- 5-carboxylic acid was reacted with C-cyclopropylmethylamine analogously to the method of Example 2b. Yield: 74 mg (36%), ίο M+H+ : 384.14. _ Example 8: • 2-(4-Phenoxyphenyl)-3H-benzoquinone. m^-5-(5-chloro-11-cephen-2-ylmethyl)guanamine 15 from 2-(4-phenoxyphenyl)-3H-benzimidazole-5-carboxylic acid and C-(5 -Chlorothiophen-2-yl)decylamine The reaction was similar to the method of Example 2b. Yield: 65 mg (26%), M+H+: 460.06. Example 9: 20 2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(thiazol-2-ylindenyl)carhamamine from 2-(4-phenoxyphenyl)-3H Benzimidazole-5-decanoic acid is reacted with C-(thiazol-2-yl)decylamine analogously to the method of Example 2b. Yield: 84 mg (37%), M+H+: 427.09. -66- 200922561 Example ίο: 2-(4-phenoxyphenyl)-3H-benzimidazole _5-(3-butoxypropyl)decylamine from 2-(4-phenoxyphenyl) -3H-Benzamidox-5-decanoic acid was reacted with 3-butoxypropylamine analogously to the method of Example 2b. Yield: in mg (46%), M+H+ : 444.17. Example 11: 2-[4-(2-Chlorophenoxy)phenyl]_3]9;-Benzimidazole-5-decanoic acid ethyl ester from 4-(2-chlorophenoxy)benzofural and 3 Ethyl 4-diaminobenzoate was reacted similarly to the method of Example 1. Yield: 1.75 g (100%), M+H+: 393.17. Example 12: 2-[4-(2-Vinylphenoxy)phenyl]_31^_benzimidazole_5-phenethylcarbamamine 12a · 2-[4-(2·Chlorophenoxy)benzene The group of -3H-benzimidazole-5-decanoic acid is reacted by [methodyloxy)phenyl]-3H-benzoxime-5-carboxylic acid ethyl ethane in a similar manner to that of Example 2a. Yield: 1.49 g (100%), Μ+Η+: 365.08. 12b : 2'[4-(2·Gaphenoxy)phenyl]-3H-benzimidazole-5-phenethyldecanoic acid amine from 2_[4_(2-phenoxy)phenyl]-3H Benzimidazole-5-carboxylic acid is reacted with phenethylamine in a similar manner to Example 2b. Yield: 65 mg (34%), M+H+: 468.36. -67- 200922561 Example 13: 2-[4-(2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-(3-indolylbutyl) decylamine 5 from 2-[4- (2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-decanoic acid was reacted with 3-mercaptobutylamine analogously to the method of Example 2b. Yield: 117 mg (66%), M+H+: 434.35. Example 14 ίο 2-[4-(2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-(2-cyclopropylethyl)guanamine 'from 2-[4-(2- The gas phenoxy)phenyl]-3H-benzimidazole-5-nonanoic acid was reacted with 2-cyclopropylethylamine hydrochloride analogously to the method of Example 2b. Yield: 79 mg (45%), M+H+: 432.33. 15 Example 15: 2-[4-(2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-(5-chlorothiophen-2-yl-methyl)carhamamine from 2-[4 -(2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-decanoic acid was reacted with 20 C-(5- gas σ-s-phen-2-yl) decylamine analogously to the procedure of Example 2b. Yield: 95 mg (47%), M+H+: 494.28. Example 16: 2-[4-(2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-(thiazol-2-ylindole-68-200922561) decylamine from 2-[4- (2-Chlorophenoxy)phenyl]-3H-benzimidazole-5-decanoic acid was reacted with C-(carbazol-2-yl)methylamine analogously to the procedure of Example 2b. Yield: 99 mg (52%), M+H+: 461.29. Example 17: 2-[4-(2-Trifluoromethylphenoxy)phenyl]_3H-benzimidazole-5-carboxylic acid ethyl ester 17a: 4-(2-trifluorodecylphenoxy)phenylhydrazine The aldehyde was taken from 4-fluorobenzaldehyde (397 mg, 3.2 mmol), 2-hydroxybenzene trifluoride (1.14 g, 7.04 mmol) and yttrium sulphate (1·4 g, 7.04 mmol) in 20 ml of DMF. Stir at 90 ° C for 6 h. The reaction mixture was concentrated in vacuo and the residue dissolved in water and ethyl acetate. The crude product obtained was purified by preparative HPLC (EtOAc EtOAc (EtOAc) Yield: 108 mg (13%%), M+H+: 267.15. 17b : 2-[4-(2-Trifluoromethylphenoxy)phenyl]_3H_benzimidazole _5-carboxylic acid ethyl ester dropwise addition of 5 ml aqueous solution containing sodium metabisulfite (71.5 mg, 0.376 mmol) To a solution of 4-(2-trifluorodecylphenoxy)benzaldehyde (1 mg, 0.376 mmol) in 10 ml of ethanol under argon. The reaction mixture was stirred at room temperature for 4 h and kept in a refrigerator overnight. The reaction mixture was concentrated in vacuo. EtOAc mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj The DMF was removed by vacuum distillation, the residue was combined with water and ethyl acetate, and the organic phase was separated, washed with water, dried and concentrated with -69-200922561. The crude product obtained was purified by preparative HPLC (EtOAc EtOAc (EtOAc) Yield: 24 mg (14%%), M+H+: 427.08. Example 18: 5 2-[4-(2-Trifluorodecylphenoxy)phenyl]-3H-benzimidazole-5-(5-chlorothiophen-2-ylmethyl)-decylamine 18a 4-(2-Trifluorodecylphenoxy)bromobenzene was dissolved in ruthenium (5.06 g, 90 mmol) dissolved in 58 ml of 17/1 DMS0/H20 mixture. The whole amount of 4-bromophenol (13.5 g, 78 ίο mmol) was added in one portion, and the mixture was stirred and stirred at 80 ° C for 5 minutes. Then, 1-fluoro-2-trifluorodecylbenzene (10 g, 61 mmol) was added dropwise rapidly, and the mixture was stirred at 120 ° C for 2 h. After cooling to room temperature, 100 ml of water was added. The aqueous phase was extracted three times with 150 mL of EtOAc. EtOAc (EtOAc)EtOAc. Yield: 13.4 g (69%), M+H+: 317.2. 15 18b : 4-(2-Trifluoromethylphenoxy)benzofural was dissolved in 4-(2-trifluoromethylphenoxy)bromobenzene (1.0 g, 3.15 mmol) under inert atmosphere. Cool to -78 ° C in 20 mL dry THF. 6.31 ml of a butyllithium solution (2N hexane solution) was added dropwise with stirring. After 5 minutes, 1.46 ml of DMF (18.9 mmol) was added and the solution was allowed to warm to room temperature with stirring. After adding 20 ml of ammonium chloride, it was extracted with dichloromethane, and the organic phases were combined, washed, dried over magnesium sulfate and concentrated. The residue was purified by chromatography (silica gel, mobile phase heptane / ethyl acetate 90: 10). Yield: 340 mg (15%), M+H+: 267". 18c : 2-[4-(2-Trifluorodecylphenoxy)phenyl]-3H-benzimidazole-5-曱-70- 200922561

Add 3,4-diaminobenzoic acid (〇.465 g, 3.〇6 mmol) and sodium metabisulfite (0_67 g, 3.612 mmol) to 4-(2-trifluorodecylphenoxy) ) benzaldehyde (0.74 g, 2.78 mmol) in 3 ml DMF solution. The mixture was stirred in a Biotage® microwave reactor for 5 min at i〇〇°c, cooled, diluted with 20 ml of ethyl acetate, and washed twice with 1 ml of water, dried over magnesium sulfate and concentrated. . Yield: 780 mg (70%%), M+H+: 399.0. 18d: 2-[4-(2-Trifluorodecylphenoxy)phenylbenzimidazole_5_(5-chlorothiophen-2-ylindenyl)methanoamine added 1,3-diethylcarbodiimide Amine (Π2.5 mg, 0.9 mmol), HOBT (172.5 mg, 0.9 mmol), triethylamine (0.25 ml) and (5-chlorothiophen-2-ylmethyl)amine (82.8 mg, 0.45 mmol) 2 ml of 2-[4-(2-trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-decanoic acid (0.1793 g, 0.45 mmol) was used. The reaction mixture was stirred overnight under warming, mixed with 20 ml of dichloromethane and washed with 10 ml of water. The residue was purified by chromatography (gluent' mobile phase gradient heptane/ethyl acetate 94: 6 to 40: 60). Yield: 87 mg (37%), M+H+: 528.0. 2〇Example 19: 2-[4-(2-Trifluoromethylphenylindenyl)phenyl]_311_benzimidazole_5-(thiophen-2-ylindenyl)-carboxamide 19a: 4-( 2-trifluoromethylphenyl hydrazide) phenylhydrazine was added to 4.43 ml of 4M hydrochloric acid solution to contain (4_[ι,3]dioxane-2-phenylbenzene-71 · 200922561 base)-(2-trifluoromethyl) The phenyl) ketone (2.0 g, 5.95 mmol) in 13 ml of the dioxane/water mixture was stirred at room temperature for 60 h. After concentrating the solvent in vacuo, the mixture was extracted with dichloromethane. 5 Yield: 1·31 g (79%), M+H+: 279.3. 19b : 3,4-Dinitro-N-thiophen-2-ylmercaptobenzamine added oxalic acid chloride (2.27 ml, 26.4 mmol) with one drop of DMF to -3 °C containing 3,4-dinitrogen Benzophthalic acid (1.0 g, 4.71 mmol) in 11 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. Residue 10 was dissolved in 11 ml of dichloropurine and pyridine (1 ml) containing p-phen-2-ylmethylamine (0.56 g, 4.95 mmol) and dichloromethane (1 ml) were added dropwise at -5 °C. 〇ml) solution. The reaction mixture was stirred at room temperature for 4 h and concentrated in vacuo. The crude product was purified by hydrazine using methylene chloride / decyl alcohol 98: 2 for mobile phase. Yield: 0.996 g (69%), M+H+: 308.0338. 15 19c : 3,4-Diamino-indole-α-cephen-2-ylmercaptobenzoylamine, 3,4-distone succinyl-hydrazine-°cephen-2-ylmercaptobenzoic acid amine (0.41 g, 1.33 mmol) was filtered and concentrated in 10 ml of ethanol/THF (1/1) in the presence of 40 mg of 10% Pd/C at room temperature for 2 h. Yield: 320 mg (97%), M+H+: 248.2. 2〇19d : 2-[4-(2-Trifluoromethylphenylindenyl)phenyl]-3H-benzimidazole-5-(thiophen-2-ylindenyl)-decylamine 3,4 -Diamino-N-thiophen-2-ylmercaptobenzamide (1 mg, 0.4 mmol) and 4-(2-trifluoromethyl-phenylhydrazino)benzaldehyde (110 mg, 0.4 Methyl) was stirred at room temperature for 2 h with 8 ml of serotonin with diethyl ethoxy iodobenzene (191 mg, 0.59 mmol) -72 - 200922561. Then diethyl ethoxy iodobenzene (191 mg, 0.59 mmol) was added and the mixture was stirred at room temperature overnight and concentrated. The residue was purified by crystallization (EtOAc, using mobile phase ethyl acetate/hexanes 1: 6). Yield: ' 168 mg (84%), M+H+ : 506.2. 5 Example 20: 2-[4-(2-Trifluoromethylbenzylidene)phenyl]-3H-benzimidazole-5-isobutylguanamine The compound was prepared in a similar manner to the above. 10 Example 23: 2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(2-cyclopropylethyl)-decylamine The present compound is similar The procedure of Example 18d was prepared by reaction with 2-cyclopropylethylamine 15. Revenue: 14%, M+H+: 466. Example 24: 2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(3-indolylbutyl)decylamine 20 This compound is analogous to Example 18d The method is prepared by reacting with 3-mercaptobutylamine. Yield: 25%, M+H+: 468. Example 25: 2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(thiazole-73 - 200922561-2-ylindenyl)guanamine The present compound A method similar to that of Example 18d was prepared by reaction with thiazol-2-ylmercaptoamine. Revenue: 40%, M+H+: 495. 5 Example 26: 2-[4-(2-Trifluorodecylphenoxy)phenyl]-3H-benzimidazole-5-(3-phenylpropyl)metholamine This compound is similar to Example 18d. The method is prepared by reacting with 3-phenylpropylamine. Revenue: 22%, M+H+: 516. 10 Example 27: 2-[4-(2-Trifluoromethylbenzylidene)phenyl]-3H-benzimidazole-5-(5-chlorothiophen-2-ylmethyl)-carbenamide 15 Example 27a: 4-(2-Trifluoromethylphenylindenyl)benzofural (4-[1,3]dioxan-2-ylphenyl)-(2-trifluoromethylphenyl) Anthrone (10_0 g, 29.7 mmol) was stirred in a mixture of 50 ml of 80:20 acetic acid:water at 65 ° C for 5.5 h. After cooling to RT, the reaction mixture was poured into EtOAc EtOAc EtOAc. The organic phase was washed with water and aq. The residue was purified by column chromatography using a heptane:methylene chloride 95:5 to 50:50 gradient. The solvent was removed to give 6.51 g of 4-(2-trifluoromethyl-benzhydryl)benzaldehyde. -74- 200922561 Example 27b: Addition of 3,4-diaminobenzoic acid to 2-[4-(2-trifluoromethylphenylf-yl)phenyl]-1 oxime-benzimidazole-5-decanoic acid (1.8 g, 11.86 mmol) and Na2S205 (2.66 g, 14.02 mmol) to a solution of 4-(2-trifluoromethylbenzoic acid) 5 benzaldehyde (3.0 g, 10.78 mmol) in 18 ml DMF . The reaction mixture was heated to 100 ° C for 3 minutes in a microwave reactor and filtered. The filtrate was concentrated in vacuo and the residue was purified eluting with EtOAc EtOAc EtOAc EtOAc After concentration, 3.49 g of 2-[4-(2-trifluoromethylbenzylidinyl)phenyl]-1H-1? benzophenanthene 0--5-carboxylic acid was obtained. M+H+: 411. 'Example 27c: This compound is based on 2-[4-(2-trifluoromethylphenyl)phenyl]-1H-benzimidazole-5-decanoic acid and 5-chlorothiophen-2-ylindenyl The amine was prepared in a similar manner to the method 15 of Example 18d. Yield: 41%, M+H+: 540. Example 28: 2-[4-(2-Trifluoromethylbenzylidene)phenyl]-1 H-benzimidazole-5-(thiazol-2-ylmethyl)-decylamine 20 This is a compound. A method similar to that of Example 27c was prepared by reaction with thiazol-2-ylmethylamine. Revenue: 19%, M+H+: 507. Examples 1, 11 and 17 are intermediates for the preparation of compounds of formula I. -75 -

Claims (1)

200922561 VII. Scope of application for patent: A compound of formula I: I 5 10 is defined as: Μ W R1-N(R2)-C(=0)_, R5-C(=0)-N(R1)- R5's(〇)o-2-N(R1)- ^ R1-N(R2)-S(0)〇.2-; 〇, CH2, 〇=〇; ^ N-R4 ' 〇λ § ; t' B ' D, Y are independently C(R3) or N , R, the middle group a, b, d, y, at most two are defined as N; f rCl6)-alkyl, (Cl_C5)-alkyl oxygen, (Crc5)-alkyl sulfur, amine, burning Base yarn, bis(CVQ)·filament, (C“C6)_filament T-amine, (C1-C6)-alkoxycarbonyl-amine, halogen, hydroxy, mono-Ci-C6)-alkyl Aminocarbonyl, bis(C 2 -C alkylaminocarbonyl, methoxycarbonyl, (Crc6)-alkylcarbonyl, cyano, trifluoromethyl-oxymethyl, (CI-C6)-alkyl Sulfonyl or aminosulfonyl; (C2-C)+morphyl, ^alkyl group can be halogen, (Crc6)-alkyl, (Ci_c3)·alkyl 1 group, (Ci_C6)-alkyl hydrogen Thio, amine, (rcc6)-alkylamino, bis-(c2-c12)-alkylamino, -(c6-c1())-aryl, -76· 20 200922561 -(C3-C12 a heteroaryl group, a -(c3-c12)-heterocyclyl group or a -(c3-c12)-cycloalkyl group, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group As desired 'to be halogen, (crc6)-alkyl, (crc3)-alkyloxy, 5 hydroxy, (CrC6)-alkyl thiol, amine, (CVC6)-alkylamine, bis-( a c2-c12)-alkylamino group substituted one or more times, (crc1())-alkyl, wherein the alkyl group is via -(c6-c10)-aryl, -(c3-c12)-heteroaryl, 10 _(匸3-(^12)-heterologous or -(C3-Ci2)-cycloalkyl substituted 'wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (crc6) -alkyl, (crc3)-alkyloxy, light base, (Ci-C6)-alkyl chlorothio, amine, (C!-C6)-alkylamino, bis-(C2-C12)- Substituted once or more than 15 times; -(c6-c10)-aryl, -(c3-c12)-heteroaryl, -(c3-c12)-heterocyclyl or _(〇3_匚12 ) - a bad alkyl group wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may optionally be halogen, (Ci_C6)-alkyl, (C1-C3)-alkyl, gas, (Ci_C6)- 20 calcined thiol, amine, (C1-C6)-alkylamino, bis-(C2-Ci2)-alkylamino substituted one or more times; R2 hydrogen, (C2-C16)-alkyl , -(C6-C10)-aryl, (CrC4)-alkylene-(C6_CI0)-aryl; or R1 and R2 The attached nitrogen atoms together form a monocyclic, saturated or -77 - 200922561 partially unsaturated 4- to 7-membered ring system or a double-ring saturated or partially unsaturated 8- to 14-membered ring system' Each member of the system can be replaced by 1 to 3 atoms or atomic groups selected from the group consisting of: _CHr4-, -CR4R5-, -(OR4)-, -NR6-, -C(=0)-, -〇-, -S-, -S0-|^_S02-; R3 hydrogen, (crC6)-alkyl, (Ci-CJ-alkyloxy, light base, (CrC6)-alkylthiol, amine, (CrC6) - anthranyl, bis-(C2-C12)-alkylamino, cyano, (CrC6)-alkylcarbonyl, halogen, trifluoromethyl, trifluoromethyloxy, (CrC6)-alkyl sulfonate Sulfhydryl, aminosulfonyl; R4 hydrogen, (CrC5)-alkyl; R5 hydrogen, (CrC16)-alkyl, amine' (cVcy-alkylamino, bis-(Ca-Cu)-alkyl Amino group, wherein the alkyl group can be via __, (Ci-Cg)-alkyl, (C1-C3)-alkyloxy, hydroxy, (CVC6)-alkyl thiol, amine, (Ci-C : sulphate, mono-(Cs-Cn)-alkylamino, -(C6-C10)-aryl, -(C3-C12)-heteroaryl, -(c3_c12)-heterocyclyl or _(c3-Ci2; Mf alkyl group substituted, wherein aryl, heteroaryl, heterocyclic Or a cycloalkyl group may optionally be halogen, (Ci-C6)-homo, (C1-C3)-alkyloxy, thiol, (CVC6)-alkylthiol, amine, alkylamine, two -(C2-C12)-alkylamino group substituted one or more times; -(C6_CI0)-aryl, -(C3_C12)-heteroaryl, -(c3-cI2)-heterocyclyl or -C3-C12) a cycloalkyl group, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may be optionally subjected to -78-200922561, a (CrC6)-histyl group, a (crc3)-alkyloxy group, a thiol group, (C) 】 _C6) _ alkyl thiol group, amine group, (crc6)-alkylamino group, bis(C2_Ci2)-alkylamino group substituted one or more times; and its physiologically acceptable salt. 2. A compound of formula j according to the scope of the patent application, wherein M Rl-N(R2)-C(=〇)., R5_C(=〇).N(R1)_, R5-S(0 〇, 2-N(R1)- n Rl-N(R2)-S(〇)0 2_ ; WO, c=o ; 10 X N-R4 ; u I is independently C(R3) or N, 15 20 wherein at most two of the groups A, B, D, Y are defined as N; R (crc16)·silk, (Cl_c5)_ silk oxygen, (CVC5)_sulphur, amine (Crcy-alkyl) Amino, bis(CVC8)-alkylamino' (Ci_c6(8) arylamino, (qQ)-alkoxy-amino, cyclin, silk, 』-(CrQ decylamine county, ^( C2_C8) _ s-amino group (cvcy aryl group, (Ci_C6m yl, cyano, trifluoro] I' 'If H (tetra) yl or amine thiol (C2_Ci 〇) _ , f, ke (4), (Ci_C6)-alkyl, (CrC3), 3 oxyl, (C1-C6)-alkyl thiol, amine, leucine, (C2~C12 )-alkylamino, -(c6-c10)-aryl-(CrCl2)__,, -(C3-C12)-heterocyclyl or -(C3-C12:M alkyl group, R1 -79 - 200922561 wherein an aryl, heteroaryl, heterocyclyl or cycloalkyl group may optionally be halogen, (cvc6)-alkyl (CVC3)-alkyloxy, hydroxy, (CrC6)-alkylthiol, amine, (Ci_c6)-alkylamino, bis-(C^C!2)-alkylamine substituted one or more times (C1-C1())-alkyl, wherein the alkyl group is -(C6_C10)-aryl, _(c3-CI2)-heteroaryl, -(Cs-C!2)-heterocyclyl or -(CrCy-cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclic or cycloalkyl may be optionally halogen, (CVC6)-alkyl, (Cl_c3)-alkyloxy, thiol, (Q- C6)-alkylthiol, amine, (Ci_c6)-alkylamino, bis-(cvce-alkylamino substituted one or more times; aryl, (CrCO-extended R2 hydrogen, (c2) -c16)-alkyl-(C6-CI0)-aryl; or R1^R2 together with the nitrogen material thereof to form a mono-, saturated or σ/no I and 4- to 7-membered ring or bicyclic Saturated or partially unsaturated to a 14-membered ring system, each member of the ring system may be replaced by 1 to 3 atoms or atomic groups selected from the group consisting of: -CHR4-, -CR4R5-, jC R4)-, -NR6 -, ((=〇)_, _〇_, _s_, _s〇 and s〇2_ ; 越, 丝 丝 丝, silk, (ci_C6)-alkane, amine group, (Crc6)-alkylamino group, two _(CVCi Shiki base wide gas base (cvc: 6) - alkyl group, halogen, trifluoromethyl, trimethyl sulfhydryl, (Cl_C6) - decyl fluorenyl, amine phosphatidyl; 20 200922561 R4 hydrogen, (CrC5)-alkyl R5 Chlorine, (cvc16)-alkyl, amine, (CrC)6)-dishylamino, bis-(C2-C12)-alkylamine, wherein the alkyl group can be dentate, (Ci_c6)-alkyl , (Ci_c3)_Hyunyloxy, thiol, (CrQ)-alkyl thiol, amine, (CVC6)-alkylamino, bis(C2-C12)-alkylamino, _(C6_Ci〇 _ aryl, _(C3_Ci2)_heteroaryl, -(q-Cu)-heterocyclyl or _(C3_Ci2)_cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl Depending on the desired halogen, (CrQ)-alkyl, (Crc3)-alkyloxy, hydroxy, (C1_C6)-alkylthiol, amine, (CVC6)-alkylamine, _(〇2< 12) The alkylamino group is substituted one or more times; and its physiologically tolerable salt. 3. A compound of formula j according to claim 1 or 2 of the patent application, wherein the definition is M R1-N(R2)-C(=0)- >R5-C(=0)-N(R1)-; W Ο, c=〇; X NH ; A, B, D, Y CH ; R (CrCi6)-alkyl, (CVCs)-alkyloxy, (CrC5)-alkylthio, amine, (crC5)- Alkylamino group, di-(C2-C8)-alkylamino group, (QQ)-alkyl group amine group, (Ci-C6)-alkoxy-Wiki-amino group, halogen, thiol group, single • (CrQ)-alkylaminocarbonyl, bis(c2_c8)•alkylaminocarbonyl, (CrC:6)-alkoxycarbonyl, (Cl_c6)-alkylcarbonyl, cyano, trifluoromethyl, Trifluoromethyloxy, (CrC6)-alkylsulfonyl or aminosulfonyl; • 81- 200922561 R1 (CrC1(])-alkyl, which gives the alkyl group -(c6-c10)-aryl a group, a -(C3-Cl2)-heteroaryl, a (C3-C12)-heterocyclyl or a _(c3_Ci2)-cyclodecyl group, wherein an aryl group, a heteroaryl group, a heterocyclic group or a cycloalkyl group may be optionally required By halogen, (CrQ)-alkyl, (Cl_c3)-alkyloxy, thiol, (Crc6)-alkylthiol, amine, (Ci_c6), alkylamine, di-(C^C) 2)-Alkylamino group substitution one or more times; R2 虱(C2-C16)-based group , _(c6_c10)-aryl, (q-CU)-alkylene-(C6-C10)-aryl; R5 hydrogen, (CrC16)-alkyl, amine, ((^(^)alkylamine a bis-(c2-c12)-alkylamino group, wherein the alkyl group is halogen, (CVC6)-alkyl, (qQ)-alkyloxy, thiol, (CVC6)-alkyl thiol, amine , (qQ)-alkyl-indolyl, mono-(Cs-Cu)-alkylamino, -(C6-C1())-aryl, -(C3-C12)-heteroaryl, -( C3_C12)-heterocyclyl or -(c3-c12)-cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (CrC6)-alkyl, (Q-C3 )-alkyloxy, hydroxy, (c "c6)-alkyl thiol, amine, (cvc6) alkylamino, bis-(C^-C)2)-alkylamino substituted one or more And its physiologically acceptable salt. 4. According to one or more of the scope of claims 1 to 3, the formula is defined as M R1-NH-C ( =0)-; W ο, oo ; X ΝΗ ; 10 A, Β, D, Υ CH ; R (CVCW-alkyl, (CrC5)-alkyloxy, (CrC5)-alkylthio, amine, ( CrC5)-alkylamino group, di-(c2-c8)-alkylamino group, (crc6)_ Base Ik-based, (Ci-C6)-alkoxy-amino, halogen, trans-, mono-(CVC6)-alkylaminocarbonyl, bis-(cvc:8)-alkylamine Alkyl, (CrQ)-alkoxycarbonyl, ((^-(: alkylcarbonyl, cyano, trifluoromethyl-fluorofluorenyl), (Ci-C6)-alkyl or acid group Renewed base; R1 (Ci-C). )-alkyl, 15 wherein alkyl is substituted by -(C6_c10)-aryl, -(cvcy-heteroaryl, -(q-Ci2)-heterocyclylcycloalkyl, wherein aryl, heteroaryl, hetero The cycloalkyl or cycloalkyl group may be subjected to alizarin, (CVQH^ group, (Cl_C3)_thyloxy, I group, (c]-C6)-homohydrothio group, amine group, (c=amine group, Di-(C2_CI2)_sucrose-substituted - one or more times 6 times, X 20 and its physiologically tolerable salt. 5. According to the patent scope, the definition is Mr1-NH-C (=〇)-; w ο, co ; to one or more of the four formulas -83 - 200922561 X NH ; A, B, D, Y CH ; R (CrC16)-alkyl, (CVCs) -alkyloxy, (CrC5)-alkylthio, amine, 5 10 15 20 (Crc5)-alkylamino, bis-(C2-C8)-alkylamino, (crc6)-alkylcarbonylamine , (CVC6)-alkoxycarbonyl-amino, halogen, hydroxy, mono-(CVC6)-alkylaminocarbonyl, bis-(c2-c8)-alkylaminocarbonyl, (CVQ)-alkoxy Carbocarbonyl, (crC6)-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (CVC6)-alkylsulfonyl or aminosulfonyl; R1 -(CH2)n-(C6 -C1())-aryl, -(C H2) n-(C3-C12)-heteroaryl, -(CH2)n-(C3-C12)-heterocyclyl or -(CH2)n-(C3-C12)-cycloalkyl, wherein aryl , heteroaryl, heterocyclyl or cycloalkyl ring may optionally be halogen, (CrC6)-alkyl, (crc3)-alkyloxy, hydroxy, (Crc6)-alkyl thiol, amine, (Crc6 _ alkylamino, bis-(Cs-C^)-alkylamino substituted one or more times; η 1, 2, 3, 4; and its physiologically tolerable salt. A combination of multiples, according to the scope of patent application Nos. 1 to 5, which are used as pharmaceuticals. - A type of medicine that contains one or more compounds that are one or more of the five orders applied for. (5) Medicine, which comprises one or more compounds according to the scope of the patent application! = in the item or item, and at least one other activity. 84 - 8. 200922561 According to the medicine of claim 8 of the scope of the patent application, which includes Other active ingredients are one or more of the following: antidiabetic agents, hypoglycemic active ingredients, HMG-CoA reductase inhibitors, cholesterol absorption inhibitors, PPARy-agonists, PPARot agonists, PPARa/Y effects^, ΡΡ ΙΙδ agonist, fibric acid derivative (senior rate), MTP inhibitor cholic acid absorption inhibitor, MTP inhibitor, CETP inhibitor, poly-human cholic acid adsorbent, LDL receptor inducer, ACAT inhibitor oxidant, Lipoprotein lipase inhibitor, Ατρ citrate lyase: preparation, f-ene synthase inhibitor, lipoprotein antagonist, ΗΜ74α as a agonist, lipase inhibitor, insulin, continued sputum, double pulse ^ "Migga eglitinide" "Securone diketone, ... enzyme enzyme inhibitor, 作用 作用 作用 作用 作用 作用 β β β β β β β β β β β 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖 糖Inhibition of glucose and glucose production (4) glycosylation 15 20 heart inhibitor, fructose-1,6-bisphosphorus: sugar 6 ::!, regulator of glucose transporter 4, inhibitor of face amine brewing aminotransferase , inhibitor of dipeptidyl peptidase W, ll-β-hydroxysteroid destabilization _ luciferase 1 Β inhibitor, = inhibitor, protein M2 modulator, GP (four) modulating reliance; Agent, acetyl-CoA carboxylase 丄=素-sensitive lipase _based kinase inhibitor, liver enzyme Ingredients, inhibitors of dilute alcohol pyruvate protein kinase cp, endothelium: %: inhibitor of sputum, inhibitor of kinase, glucoside f hormone = reading antagonist, sputum agent, NPY agonist, brain Promoter, CART promotes agonist, H3 -85- 200922561 agonist, TNF agonist, CRF agonist, CRF BP antagonist, urocortin agonist, CB1 receptor antagonist, β-3 agonist, MSH (melanocyte stimulating hormone) agonist, CCK agonist, serotonin reuptake inhibitor, mixed serotonin-induced and positive-renal adrenaline a lead compound, a quinone agonist, a campanin agonist, a sorghum curcumin antagonist, a growth hormone, a compound that releases growth hormone, a TRH agonist, a decoupled protein 2 or 3 modulator, Obesity protein agonist, DA agonist (bromocriptine, D opr exin), lipase/housemic enzyme inhibitor, PPAR regulatory LYO, RXR modulator or TR-β Activating agent or amphetamine. 10. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for the treatment of obesity. 11. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for the treatment of diabetes. 15 12. Use of a compound according to one or more of claims 1 to 5 for the preparation of a lipid-lowering pharmaceutical product. 13_ - The use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for treating metabolic syndrome. 14. Use of a compound according to one or more of items 1 to 5 of the scope of the patent application for the preparation of a medicament for the treatment of insulin resistance. 15. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for the treatment of cardiovascular diseases. 16. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for treating a CNS lesion. -86- 200922561 17. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for the treatment of schizophrenia. 18. Use of a compound according to one or more of claims 1 to 5 for the preparation of a medicament for the treatment of Alzheimer's disease. 5 19. A method of making a medicament comprising one or more compounds according to one or more of claims 1 to 5, which comprises mixing the active ingredient with a pharmaceutically suitable carrier and converting the mixture to form a suitable The type of medication. 20. Use of a compound of formula I: The definition is: M R1-N(R2)-C(=0)-, R5-C(=0)-N(R1)-, 15 R5-S(O)0-2-N(Rl)- , R1-N(R2)-S(0)〇_2-, may comprise from 2 to 4 heteroatoms selected from the group consisting of: heteroatoms in the N, oxime, and S groups, wherein the heterocyclic ring may pass (CrC16)- Alkyl or double bond oxygen substitution; W 0, CH2, c=o; X N-R4, Ο, S; 20 A, B, D, Y are each independently C(R3) or N, wherein groups A, B Up to two of D, Y are defined as N; -87- 200922561 R Hydrogen, (CrC16)-alkyl, (CVC5)-alkyloxy, (crc5)-alkylsulfide, amine, (CrC5) -alkylamino, bis-(C2-C8)-alkylamino, (crc6)-alkylcarbonylamino, (crc6)-alkoxycarbonylamino, halogen, hydroxy, mono-(Q-C6 -alkylaminocarbonyl, bis(C2-C8)-alkylaminocarbonyl, (Ci-Q)-alkoxycarbonyl, (Crc6)•alkylcarbonyl, cyano, trifluoromethyl, tri Fluoromethyloxy, (CVC6)-alkylsulfonyl or aminosulfonyl; R1 (C2-C1())-fluorenyl, wherein alkyl can be halogen, (C^Cd-alkyl, (crc3) -alkyloxy, hydroxy, (CrC6)-alkyl thiol, amine, (crc6)-alkylamino, bis-(c2-c12)-alkyl , -(C6-C1G)-aryl, -(C3-C12)-heteroaryl, _(c3_Ci-heterocyclyl or _(c3_Ci2)_cycloalkyl substituted, wherein aryl, heteroaryl, hetero The cyclo or cycloalkyl group may be optionally subjected to i, (CVC6)-alkyl, (Cl_c3)-alkyloxy, per group, (CVC: 6)-alkylthiol, amine, (Ci_c6)-alkane. The amino group, the bis-(C2-C1; 2)-alkylamino group is substituted one or more times, (CrC 〇)-alkyl, wherein the alkyl group is -(CVCi0)_aryl, _(C3_Ci2) _heteroaryl, -(CVCl2)-heterocyclyl or -(cvcy-cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkylcanonin, (Crc6)-mercapto, ( Ci_c 纽基oxy, thiol, (CrC6)-alkyl thiol, aminoalkylamino, bis(^^2)-alkylamino substituted once or -88- 200922561 multiple times; -( C6-C10)-aryl, _(c3_Cl2)_heteroaryl, _(CVCi2)^cycloalkyl or -(C3-C12)-cycloalkyl, 5 wherein aryl, heteroaryl, heterocyclyl or ring The alkyl group may be optionally halogenated, (Crc6)-alkyl, (Crc3)_household oxygen, thiol, (Ci_C6)_alkylthiol, amine group, (cvcd-alkylamine group, bis(C2_Ci2) )_ 炫基基基取One or more times; R2 hydrogen, (C2-C16)-alkyl, -(c6-c1{))-aryl, alkyl-(C6-C1())-aryl; 10 or R1 and R2 The attached nitrogen atoms together form a monocyclic, residual and partially unsaturated 4- to 7-membered ring system or a bicyclic saturated or partially unsaturated 8- to 14 membered ring system, wherein each of the ring systems A member of the group can be replaced by three atomic or atomic groups selected from the group consisting of: _CHR4-, -CR4R5-, _(〇R4)-, -NR6-, -C(:〇)-, _〇_, _s_, _s〇_ and _s〇2_ ; 15 R3 hydrogen, (CrC6)-alkyl, (CVQ)-alkyloxy, hydroxy, (Ci_C6)-alkylthiol, amine, (crC6)-alkylamine , bis(C2-Ci2)-alkylamino, cyano, (CrC6)-alkylcarbonyl, halogen, trifluoromethyl, trifluoromethyloxy, (CrC6)-alkyl sulphate, amine sulfonate Mercapto; 20 R4 nitrogen, (C1-C5)-alkyl; R5 hydrogen, (CrC16)-alkyl, amine, amide, bis-(Cs-Cn)-alkylamino, wherein alkyl Alizarin, (Cl_C6)-alkyl, (CrC3)-alkyloxy, hydroxy, (crc6)-alkyl thiol, amine, (crc6)-alkylamino, bis(C2-C12)- Acrylamine, -(C6-C1G)-aryl , -89- 200922561 (C3_Cl2)·heterocyclyl or —(c3-c12)-cyclo-(C3-C12)-heteroaryl, _alkyl substituted, wherein aryl, heteroaryl, heterocyclyl or Cycloalkyl can be regarded as Hi-' (cvc: 6) H (Ci <: 3M thiol, residue, (CVC6)-alkylthiol, amine, (Ci_c6) _ alkylamino, di- (CVC) 2)-alkylamino group-substituted times; 10 -(c6-c1())-aryl, _(c3_Ci2)_heteroarylheterocyclyl or -(C3-C12)-ring The aryl group, heteroaryl group, heterocyclic group or cycloalkyl group may be optionally halogen, (匸1-匸6)-homogeneous, (Ci-Cj-alkyloxy, thiol, (CpC6) alkyl hydrogen a thio group, an amine group, a (rcc6)-alkylamino group, a bis(C2, e^alkylamino group substituted one or more times; and a physiologically tolerable salt thereof, which is used in the manufacture of a therapeutic obesity医医15 Product 0 21. The use of the compound of formula j according to claim 20 of the patent application, wherein M R1-N(R2)-C(=0)-, R5-C(=〇)-N (Rl>, R5-S(0)〇-2_N(R1)-, Rl-N(R2)_S(〇)〇-2- ' may contain 2 to 4 selected from: N, Ο, S group Heterocyclic heterocycle, wherein the read heterocycle can pass (CrC1 6)-Alkyl or double bond oxygen substitution; W 0, c=o, X N-R4 ; A, B, D, Y are each independently C(R3) or Μ, 20 200922561 R 5 R1 10 15 20 A maximum of two of the group VIII and 134 are defined as Jiang C) _ burnt base, (CrC5) _ burnt oxygen, ((vc sulphur, amine:, (CrC5)-alkylamino, two ( C2_C8) _ mercaptoamine group, 'from alkyl group amine group, (QQ) to oxy group amine group, _ 素, 拜 、, = (CVC6) _ s s s Amino group ^, 〖-Q) j complete oxycarbonyl, (. {C-alkylcarbonyl, cyano, trifluoromethyl-fluoromethyloxy, (CrC6)-homoyl fluorenyl or amine aryl; (C2-C1Q)-alkyl, wherein the alkyl group can be halogenated , (Cl_C6)-alkyl, (Ci_c3)-alkyloxy, thiol, (CrC6)-alkyl thiol, amine, (Ci_c6)-alkyl group, mono-(C2-C12)- Amino group, _(c6_c10)-aryl, _(C3-C12)-heteroaryl, -(C3-C12)-heterocyclyl or _(c3_c12)-cycloalkyl substituted, wherein the radical The base, heterocyclic group or cycloalkyl group may optionally be halogen, (CVC6)-alkyl, (c"c3)-alkyloxy, hydroxy, (CVC6)-alkylthiol, amine, (Cl_c6)_ Substituting one or more times with a sulfhydrylamino group, a _(C2_Ci2)-burnt amine group; (C1-C10)-alkyl group, wherein the alkyl group is -(C6-Ci〇)-aryl, -(C3- C12)-heteroaryl, (C3-C12)-heterocyclyl or -(C3_Ci2)-cyclohexyl substituted 'wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (Ci_C6) -alkyl, (C1-C3)-alkyloxy, hydroxy, (CVC6)-alkyl thiol, amine, (CrQ)--91- 200922561 alkylamino, bis-(C2-Ci2)_ Substituting a sulfhydryl group once or Multiple times; R2 hydrogen, (c2-c16)-alkyl, -(C6-C10)-aryl, (CrC4)-alkylene-(c6-c1())-aryl; 5 or R1 and R2 The attached nitrogen atoms together form a monocyclic, saturated or partially unsaturated 4- to 7-membered ring system or a bicyclic saturated or partially unsaturated 8- to 14-membered ring system in which the members of the ring system It may be replaced by 1 to 3 atoms or atomic groups selected from the group consisting of -CHR4-, -CR4R5-, -(C=R4)-, -NR6-, -C(=0)-, -0-, -S-, -SO- and -S02-; i〇R3 nitrogen, (C1-C6)-alkyl, (C1-C3)-alkyloxy, thiol, (C1-C6)-alkylthio , amine group, (Ci_C6)-alkylamino group, di-(C2-C12)-alkylamino group, gas group, (Ci_C6)-dishyl group, halogen, trifluoromethyl, trifluorodecyloxy , (Q-C6)-alkylsulfonyl, aminosulfonyl; R4 hydrogen, (CrC5)-alkyl; 15 R5 nitrogen, (Ci_Ci6)-dishyl, amine, (Ci_Ci6)-alkylamine , bis-(C2-C12)-andylamino" wherein the alkyl group may be halogen, (CVC6)-alkyl, (crc3)-alkyloxy, hydroxy, (CrC6)-alkyl thiol, amine , (CrC6)-alkylamino, bis-(C2-C12)-alkylamino, -(C6 _Ci. -aryl, -(C3-C12)-heteroaryl, 20-(c3-c12)-heterocyclyl or -(C3-C12)-cycloalkyl, wherein aryl, heteroaryl, heterocycle The base or cycloalkyl group may optionally be halogen, (rcc6)-alkyl, (crc3)-alkyloxy, hydroxy, (crc6)-alkyl thiol, amine, (C "C6"- s (amine) Substituted, di-(C2-Ci2)-alkylamino group substituted one or more times; -92- 200922561 and its physiologically tolerable salt, which is used in the manufacture of a medicament for the treatment of obesity. The use of the compound of formula I in claim 20, wherein it is defined as 5 M R1-N(R2)-C(=0)-, R5-C(=0)-N(R1)-; X ο, oo X N-R4 ; A, Β, D, Υ are each independently C(R3) or N, wherein at most two of the groups A, B, D, Y are defined as N; ίο R mouse, (C1- C16)-alkyl, (C1-C5)-alkyloxy, (C-C5)-alkyl hydrazine, amine group, (C1-C5)-alkylamino group, bis-(C2-C8)-burning Amino group, (CpC6)-alkylcarbonylamino group, (crc6)-alkoxycarbonylamino group, halogen, hydroxy group, mono-(Ci_C6)-alkylamino group, di-(C2-Cs)- Anthranyl-based prison base, (Ci_C6)-burning oxygen prison base, (Ci- C6)-alkyl group, cyano group, trifluoroindole 15 group, di-mercapto oxygen, (Ci-Ce)-alkyl group or amine group; R1 (C2-C1G)-alkyl , wherein the alkyl group may be halogen, (CVQ)-alkyl, (CVC3)-alkyloxy, light base, (Ci_C6)-alkylthiol, amine, (Ci_C6)-alkylamino, di- (C2-C12)-alkylamino, -(Cg-Cio)-aryl, 20-(C3-Ci2)-heteroaryl, -(C3-C12)-heterocyclyl or -(C3-C) 2)-cycloalkyl substituted, wherein an aryl, heteroaryl, heterocyclyl or cycloalkyl group may optionally be halogen, (crc6)-alkyl, (crc3)-alkyloxy, light base, (C!- C6)-alkylthio group, amine group, (Ci_C6)_-93- 200922561 alkylamino group, bis-(Cz-C!2)-alkylamine group substituted one or more times; (CrC10)-alkane a group in which the alkyl group is substituted by _(c6_Ciq)-aryl, _(VCi2).heteroaryl, mono(CVCl2)-heterocyclyl or -(C3-C12)-cycloalkyl, wherein aryl, Heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (Ci-C6)-alkyl, (crc3)-alkyloxy, hydroxy, (Crc6)-alkyl thiol, amine, (Ci_c6 )_alkylamino, bis(C2_Ci2)-alkyl Substituting one or more times; R2 wind, (C2-C16)-alkyl, _(C6_Ci〇)_aryl, (Ci_c4)_alkyl aryl; or = and R2 together with the nitrogen atom Forming a monocyclic, saturated or 4-unsaturated 4- to 7-membered ring system or a bicyclic saturated or partially unsaturated 8 to 14 membered ring system, wherein each member of the ring system can be selected from 1 to 3 Substitution from the following atom or atomic basis: _CHR4_, _CR4R5_, _(C=R4)-, _NR6_, -C(=〇)_, _〇_, _s---S0-^-S02-; R3 hydrogen, (CrC6)-alkyl, (Cl_c3)-alkyloxy, hydroxy, (Ci_c6)-alkylthiol, amine, (crc6)-alkylamino, bis-(C2-C12)-alkylamine Base, cyano group, (CrC6)-alkyl group, dentate, trifluoromethyl, trifluoromethyloxy, (CrC6)-alkylsulfonyl, aminosulfonyl; R4 hydrogen, (CrC5) -alkyl R5 hydrogen, (CrC16)-alkyl, amine group, (Cl_Ci6)j-amino group, di-(C2-Ci2)-alkylamino group, -94- 200922561 wherein the alkyl group can be halogenated, (crc6 -alkyl, (crc3)-alkyloxy, hydroxy, (Ci-C6)-alkylthio group, amine group, (Ci-Cg)-alkylamino group, di-(C2-C12)-burning Amino group - (C6_Ci. -aryl, -(C3-C12)-heteroaryl, '-(c3-c12)-heterocyclyl or -(c3-c12)-cycloalkyl substituted, 5 wherein aryl, heteroaryl, hetero A cycloalkyl or cycloalkyl group may optionally be halogen, (Q-C6)-alkyl, (CVC3)-alkyloxy, hydroxy, (crc6)-alkylhydrocarbyl, amine, (Ci-Cg)-hospital The amino-amino group, the di-(C2-C12)··alkylamino group are substituted one or more times; and the physiologically tolerable salt thereof is used in the manufacture of a pharmaceutical product for treating obesity. 23. Use of a compound of formula I according to claim 20, wherein M R1 -N(R2)-C(=0)-, R5-C(=0)-N(R1)-; Ο, C=0; 15 X N-R4 ; A, B, D, Y CH ; R hydrogen, (cvce-alkyl, (q-Cs)-alkyloxy, (cvcy-alkylthio, amine, (C1-C5)-alkylamino, bis-(C2-C8)-alkylamino, (C!-C6)-alkylamino, (Ci-Cg)-alkoxyamine , halogen, per group, 20 hr-(Ci-Cg)-alkylamino group, bis-(C2-C8)-alkylamino group, (crc6)-alkoxycarbonyl, (crc6) An alkylcarbonyl group, a cyano group, a trifluoromethyl group, a trifluorodecyloxy group, a (crc6)-alkylsulfonyl group or an aminosulfonyl group; R1(C2-C1Q)-alkyl, wherein the alkyl group is Halogen, (crc6)-alkyl, (crc3)-alkyl-95- 200922561 Oxygen, hydroxy, (crc6)-alkyl thiol, amine, (crc6)-alkylamino, di-(C2- C12)-alkylamino, -(C6-C10)-aryl, (C3-C12)-heteroaryl, -(C3-Ci2)-heterocyclyl or -(C3-C12)-cyclo'alkyl Substituted, 5 wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (crc6)-alkyl, (crc3)- Substituting one or more times with an alkyloxy group, a trans group, a (Ci-C6)-alkylthio group, an amine group, a (Ci_C6)-alkylamino group, a bis-(C2-C12)-alkylamino group; (crc1())-alkyl, wherein alkyl is via -(c6-c10)-aryl, -(c3-c12)-heteroaryl, -(C3-C12)-heteroyl or-(〇 3-〇12)-bad alkyl substituted 5 wherein aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be halogen, (Q-C6)-alkyl, (Q-C3)-alkyloxy, 15 Substituted one or more times by (Ci_C6)-alkylthio group, amine group, (Ci_C6)-alkylamino group, bis-(C2-C12)-alkylamino group; R2 hydrogen, (C2- C16)-alkyl, -(C6-C10)-aryl, (CrC4)-alkylene-(C6-Ci〇)-aryl; 2〇 or R1 and R2 together with the nitrogen atom to which they are attached form a single a cyclic, saturated or partially unsaturated 4- to 7-membered or double-ring saturated or partially unsaturated 8- to 14-membered ring system in which each member of the ring system may be selected from 1 to 3 Substitution of atoms or atomic groups: -CHR4-, -CR4R5-, -(OR4)-, -NR6-, -C(=0)-, -0-, -S-, -SO- and -S02-; -96- 200922561 R4 hydrogen; R5 nitrogen, (Ci_Ci6)_alkyl, amine, (C -Ci6)-alkylamino, bis(C2_Ci2)- leumino, 'wherein alkyl can be halogen, (CrC6)-alkyl, (CVC3)-alkyl 5 oxy, thiol, (Ci- Cg)-calcinyl thiol, amine, (Ci-Cg)-alkylamino, bis-(C2-C12)-alkylamino, -(C6-C10)-aryl, -(C3- C12)··heterocyclyl, —(C3-C!2)_heterocyclyl or —(C3-C12)··cycloalkyl substituted, wherein aryl, heteroaryl, heterocyclyl or cycloalkyl is visible 10 to be halogen, (Crc6)-alkyl, (Q-C3)-alkyloxy, fenyl, (Ci_C6)-alkyl thiol, amine, (Ci_C6)-alkylamino, two - (C2-C12)-alkylamino group substituted one or more times; and its physiologically tolerable salt, which is used in the manufacture of a pharmaceutical product for the treatment of obesity. 24. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of diabetes. 25. Use of a compound of formula I according to one or more of claims 20 to 23 of the patent application for the manufacture of a lipid-lowering pharmaceutical product. 20 2 6. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of metabolic syndrome. 27. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of insulin resistance - 97-200922561. 28. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of cardiovascular diseases. 5 29. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of CNS lesions. 30. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of schizophrenia. 1〇 31. Use of a compound of formula I according to one or more of claims 20 to 23 for the manufacture of a medicament for the treatment of Alzheimer's disease. • 98 - 200922561 IV. Designated representative map: (1) The representative representative of the case is: (No). (2) A brief description of the symbol of the representative figure: None 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: I