PL145710B1 - Method of obtaining novel bicyclic piperidine derivatives - Google Patents

Description

The subject of the invention is a process for the preparation of new, bicyclic pyridine derivatives of the general formula I, in which the group -A1 = A2-A * = A4- represents a divalent radical of the formula -CH = CH-CH = CH-, -N = CH-CH = CH-, -CH = N-CH = CH-, -CH = CH-N = CH- or -CH = CH- -CH = N-, in which radicals 1 or 2 hydrogen atoms can be replaced identical or increasing substituents, such as halogen atoms, lower alkyl radicals, lower alkoxy groups or hydroxyl groups, R 1 is hydrogen, lower alkyl, cycloalkyl, aryl, lower alkyl substituted with aryl or a diphenylmethyl radical, where R as the aryl radical is a phenyl radical, possibly having 1 or 2 substituents such as halogen atoms, lower (alkyl radicals, lower alkoxy groups or trifluoromethyl groups, or is a thienyl group, optionally substituted with a halogen or other alkyl radical, or is a furyl group; optionally substituted with a lower alkyl radical, or is a pyridinyl, pyrazinyl, thiazolyl or naphthyl group, R2 is a hydrogen atom or a lower alkyl radical, and L is a group of formula II, in which the symbols ris are the same or different and each of them represents a number zero or an integer 1-6 and one or two hydrogen atoms in the bivalent radical 2 -CsH2s- may be replaced independently of each other by hydroxyl groups, lower alkoxy groups, phenyl radicals or chlorophenyl, T is a substituent of the symbol -Y- or a group of the formula -ZC / = X / -Y'- where Y is an oxygen atom, a direct bond or a group of the formula = NR8 in which R3 is hydrogen, lower alkyl, lower alkylcarbonyl, furylcarbonyl, group of formula Ar 2 -lower alkyl or Ar 2 -carbonyl, in which formulas Ar 2 is a phenyl radical, optionally having up to three substituents of the same or miscellaneous, vol such as halogen atoms, hydroxyl, nitro, cyano, trifluoromethyl groups, lower alkyl, alkoxy or alkylthio groups, mercapto groups, alimino or carboxyl groups, lower mono- or diikylamino groups, lower alkoxycarbonyl or alkylcarbonyl groups Y 'represents an oxygen atom, the group R = NH or a direct bond, X represents an oxygen atom, a sulfur atom or a group of the formula = NR4, where R4 represents a hydrogen atom or a lower alkyl radical and Z represents an oxygen atom, a direct bond or a group of formula 25 = NR5, where R5 is hydrogen or a lower alkyl radical and L1 in formula II is hydrogen or halogen, cyano, ilisocyanate, isothiocyanin, thienylcarbonyl, cycloalkyl, naphthyl or above. the described Ar2 group or the Ar2-isulfonyl group in 145 710 145 710 where Ar2 is as defined above, whereby when r is zero then L1 may also be a lower alkenyl group, a lower Ar2-alkenes group. The meaning of Ar2 has the meaning given above, and it is substituted by two lower alkoxy groups, or L1 is A group, pfridinyl, pwd, optionally containing 1 or 2 ifectal and orbo Three substituents, such as halogen atoms, amino groups, lower alkyl or alkoxy groups, pyridinyl oxide group, optionally substituted mitro group, pyrimidinyl group having 1 or 2 identical or different substituents, such as halogen atoms, amino groups and lower alkyl or alkoxy groups, a pyridazimyl group, optionally substituted with a lower alkyl radical or halogen atom, a pyrazinyl group, optionally substituted with a halogen atom, amino or lower alkyl, thienyl, optionally substituted with halogen or lower alkyl, furyl, optionally substituted with lower alkyl or halogen, pyrooyl, optionally substituted with lower alkyl, thia - a solyl, optionally substituted with a lower alkyl radical, a lower alkoxycarbonyl group, or a group with the symbol Ar2 described above, a tefcrazolthyl group, optionally substituted with a lower alkyl group, an imidiazodil group, optionally having 1 or 2 identical or different substituents, such as lower alkyl radicals or nitro groups, a 4,5-diihydro-5 group -keto-1H-tetraZo, optionally substituted with lower alkyl, chiolinyl, optionally substituted hydroxyl or lower alkyl, phthalazinyl, optionally substituted with halogen, morpholinyl, 21,3-dihydro -3-keto-4H-benzo-xazine, group B, 3-dihydro-1,4H-benzodioxin-group, dioxanyl group, group 2-keto-2H-1-foensopyranyl, group 4-ketx-4tH-1-benzopyran - I, 2,4-soap-2i, 4-dice, 3 (1H) -pyrimidinyl group, 4-keto-2 (1H) -pyrimidinyl group, 2-keto-3-oxazoylidinyl group or a group pe indole or also Het is a group of formula 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h or 3i, where X2 in formulas 3.a 3b, 3c and 3ih is oxygen or sulfur atom and in formula 3a the substituents X2 may be the same or different, the substituents R11, R12, R14, R15, R22 and R24 respectively in the formulas 3a R11 and R12 may be the same or different, the substituents R1 *, R18, R17, R18, R19, R20, R21 and R »respectively in the formulas 3b, 3c, 3d, 3e, 3f and 3g are hydrogen atoms, lower alkyl radicals, hydroxyl groups, mercapto groups, lower alkoxy or alkylthio groups or halogen atoms, where R17 and R18 in formula 3d and R19 and R20 in formula 3e may be the same or different, G1 in formula 3a represents the group —CH = CH- —CH = CH—, -hS — CH = = CH— or —N = CH — NH, and G2 in formula 3d represents the group —HCH = CH — CH = CH— —S— CH2 / 2—, —SyCH2 / 3—, - / CH2 ^ 4— or - ^ S ^ CH = CH—, G3 in formula 3e represents the group —CH = CH — CH = CH—, —CH2 ^ NH-H, CH2 / 2—, -hS ^ CH = CH— or —N = 5 = CH — CH = CH—,. G4 in formula 3 and represents the group —CH2 — NH— / CH2 ^ 2—, —N = CH- ^ CH = CH—, - ^ CH = N ^ CH = C H— - ^ CH = CH — N = CH—, —CH = CH-hCH = CH—, - ^ CH = CH- ^ CH = N—, - ^ ST = = CH — N = CH— or --CH = N- ^ CH = N-, G5 in formula 3 g represents the group - (N = CH-hCH = CH-, ^ GH = N- ^ CH = CH, -CH = OH- ^ N = CH-, - CH = = CH — CH = N, —CH = CH-hCH = CH, -, N = CH — N = = CH— or —CH = N- ^ CH = N— and G6 in formula 3 and h is the group - ^ CH = CH — CH = CH—, - ^ N = 15 = CH- ^ CH = CH—, - ^ CH = N ^ CH = CH—, —CH = = CH — N = CH—, —CH = CH — CH = N—, —N = CH— —N = CH— or - ^ CH = N ^ CH = iN—, where one or two hydrogen atoms in these G1-Gfl groups or in the benzene ring in groups of formulas 3b, 3c and 3d can be replaced by lower alkyl, alkylthio or alkoxyl groups or halogen atoms, and if they are bound to nitrogen atoms, they can be replaced by lower alkyl radicals, while the pa group of the above-described formula CH2s at the atom in - a group of the above-described formula CsH2s on the carbon atom, which could have the substituent R11, R12, R17, R18, R19, R20, R21, R22 or R2 *, respectively, then the substituents of these symbols are absent, but : i) when L1 is hydrogen and T represents the group of the formula (Z — C) = X) —Y1, in which Y 'is as defined above, but except for a direct bond, Z is oxygen and X is oxygen or sulfur, where R in formula II is an integer 1-6, or ii) when L1 is a halogen atom, an isocyanate group, an isothiocyanate group, or the above-described Het group bound to the above-described group of the formula CrH ^ r on the nitrogen atom and when r is zero then T is a direct bond or a group of the above-described formula —CSX = I — Y 'and when iii) T is the symbol Y or a group of formula —Z— —C / = X / —Y' and Y or Y 'are as defined above, but except for direct linkage then s in formula II is an integer of 1-6.50 It is also within the scope of the invention to prepare phannacologically acceptable addition salts of compounds of formula I. with acids or stereoisomers of these compounds. The compounds according to the invention are antihistamines and antagonize tami serotonin (also known to be highly useful in the treatment of allergic diseases). Zj. Am. No. 4,219,659 discloses the N-heterocyclyl-4-pipydinamine derivatives 60 of the formula VI, which also have an anti-hilstamine effect. The structure of the compounds according to the invention differs from those known compounds, in particular the 4-piperidinyl substituent, which is always the bis-ring 65 Vheterocyclic L-methyl- or / heterocyclyl Z-hetero-5 145 710 6 group, and also that they are also with eight serotonin antagonists. With respect to the compounds of formula I, the term "halogen" means fluorine, chlorine, bromine or iodine, the term "lower alkyl" denotes saturated hydrocarbon radicals with 1 to 6 carbon atoms having a straight chain or branched, for example, methyl, ethyl, 1-methylethyl, 1,1-dimethylethyl, propyl, 2-methylpropyl, butyl, pentyl and hexyl radicals. The term "alkyl" denotes the above-described lower alkyl radicals and the higher homogeneous radicals thereof with 7-10 carbon atoms, and the term lower alkenyl radical "denotes straight or branched hydrocarbon radicals with 2 to 6 carbon atoms, such as e.g. 2-propenyl, 2-butenyl, 3-butenyl and 2- * pentenyl. The term "cycloalkyl" denotes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl radicals, and the term "divalent lower radical" denotes straight or branched chain radicals having 1-6 carbon atoms. it is obvious that compounds containing as the group L1 as the above-described group Het, may contain the group Het unsaturated or partially or completely saturated. they may contain a tautomeric ketone-enol or vinyl log system, and may also be in the ketone or enol form. the meaning given above, X 1 represents an oxygen atom or a = NH group, and W represents a chlorine or bromine atom or an alkoxy or hydroxy group, and is reacted in an inert medium of the solvent. from a diamine of the formula V, in which R 1 and the group of the formula —A1 = A2 — A * = A4 — have the meaning given above. These reactions are carried out by force in a solvent such as alcohol, especially methanol or ethanol, or such like an acid, preferably acetic acid. If a compound of formula IV is used in which W is hydroxy, the reactions are carried out in the presence of a dehydrating agent such as, for example, polyphosphoric acid or phosphorus oxychloride, and optionally in the presence of a base such as, for example, N, N -idimethylbenzylamine) and a. The compound of formula I obtained is optionally converted by known methods into its acid addition salt, in particular into a pharmacologically acceptable salt. The products of the invention can be separated from the reaction mixture and, if necessary, further purified from There are generally different methods. Compounds of formula I are basic in nature and can also be converted into pharmacologically active, non-toxic acid addition salts. For this purpose, these compounds are treated with suitable inorganic or organic acids, for example with hydrobromic acid, in particular hydrochloric or hydrophobic acid, sulfuric acid, nitric acid, phosphorus acid. acetic, propionic, hydroxyacetic, 2-i hydroxypropionic, pyruvic, oxalic, malonic, amber, cis-ethylene dicarboxylic, fumair, apple, wine, lemon, methanesulfone, ethanesulfone, bansenosiphone -methylbenzenesoylphonic, cyclohexylsiphaminic, 2-hydroxybenzoic, 4-amMo-2-hydroxybenzoic and the like, and Conversely, it is possible to produce free compounds of formula 1 from salt by treatment with alkalis. According to the invention, they are known compounds and can be produced by methods known to those known as amological to the known ones, some of which are novel compounds and some of their preparation methods are given below. For example, compounds of formula IV in which X1 is = NH, W is lower alkoxy and L and R2 are as defined above can be prepared by reacting a piperidine derivative of formula VII in which L and R1 are as defined above, with lower alkyl, eg methanol or ethanol, in the presence of an acid, eg hydrochloric acid. 25 From formula l it can be seen that the compounds produced by spo-. they may have several asymmetric carbon atoms according to the invention. Each of these chiral agents may have the R and S configurations according to; the regulations given by R. S. Cahn. 30 C Iingold and V. Preleg in Angew. Cham., Int. Ed.Engl., 5, 385, 511 (1956). Stereochemically pure isomeric forms of the compounds of formula I can be obtained by known methods. Diastereoisomers can be separated by physical methods such as selective crystallization and by chromatographic methods, e.g. anti-current separation, and enainiomers can be separated by the selective crystallization of their diastereoisameric stoics with optically active acids. It is also known to prepare by using the corresponding stereochemically pure isomeric forms of the starting products, as long as the reaction takes place stereospecifically. It is obvious that diastereomeric cis and trans racemates can be further resolved into optical isomers aisi / + /, cils. / - /, trans / + / and trans / - /, using known methods. The preparation of sitereoisomers of the compounds of formula I is within the scope of the invention. The Examples which follow illustrate the invention. Parts listed in the examples are parts by weight unless otherwise indicated. The examples in 1-5 illustrate the preparation of intermediates, and in the following examples the preparation of the compounds of formula I, each of which has a sequential number in parentheses. These numbers are used 60 when describing attempts to illustrate the activity of these compounds. In some examples, after the amount of the obtained compound in parts, the percentages in brackets are given to denote the yield of a given process in relation to the theoretical yield. 145,710 A. Production of starting products. Example I. a) Month 302 parts of 2- [l-nylmethyl) -4-piperidine-Hdeno] -acetic acid ethyl ester hydrochloride and 200 parts of glacial acetic acid are hydrogenated under atmospheric pressure at 24-36 ° C in the presence of 4 parts of oxide of platinum and after uptake of the calculated amount of hydrogen, the catalyst is filtered off and the filtrate is evaporated. The residue is rinsed with diethyl ether, made alkaline with sodium hydroxide and extracted with diethyl ether. The extract is dried over tassed carbonate, evaporated and the oily residue distilled under reduced pressure, yielding 205 parts of the oily slower base crude. 1 part of this product is used to form the hydrochloric acid salt. Namely, this product is dissolved in diethyl ether and gaseous hydrogen chloride is introduced into the solution, causing precipitation of the semi-solid salt. The solvent is separated by decantation, the remainder is dissolved in a mixture of 6 parts of ethanol with 4 parts of diethyl ether, the solution is made to 5 parts and 12 parts of diethyl ether are added, causing the precipitation of the half-salt. The solvent is separated by decantation, the residue is dissolved in a mixture of 6 parts of ethanol with 4 parts of diethyl ether, the solution is concentrated to 5 parts and 12 parts of diethyl ether are added, causing the solid to precipitate. This product was filtered off and dried, yielding 0.2 parts of 1- (phenylmethyl) -4-piperidinooietic acid ethyl ester hydrochloride, mp 122.5 ° -107 ° C. b) A mixture of 8 parts of ester hydrochloride. 1- (phenylmethyl) -4-piperidine acetic acid ethyl ester and 80 parts of dilute hydrochloric acid are boiled under a refrigerator and stirred for 4 hours, then cooled and evaporated. The remainder is washed. 2-propanol, the solvent is evaporated desirably, a solid residue is once more evaporated. washed with 2-propanone, filtered and dried to give 6 parts of acid hydrochloride, mp 137-145 ° C. 45 EXAMPLE II 2 (350 parts of hydrogen chloride are passed through 5600 parts of ice-cooled ethanol, then 1500 parts of l- / phenylethio / -pi, peridine acectriitrile-4 are added dropwise over 45 minutes and stirred at room temperature at 50). for 20 hours.Then the mixture is evaporated, the residue is mixed with 2400 parts of acetonitrile, drained, the product is washed with 560 parts of acetonitrile and dried to give 2000 parts (85.7%) of 1-w - (phenylmethyl) -4-priperidine hydrochloride. 1-phenylethyl dihydrochloride (methyl O 2-methylmethyl) 4-piperidine ethanimidate is also prepared in an analogous manner. Example III. 180.0 parts 2-chloro-3. niitroipyridine, 122.0 parts of 2-thiophenomethylamine, 191.0 parts of sodium carbonate, 1 part of potassium iodide and 810 parts of N, N-vumethylacetamide are mixed at 100 ° C for 1.5 hours. then poured into about 4,000 parts of water and stirred at room tem- peraturee overnight. the precipitate is filtered off and dried at 40 ° C under reduced pressure, obtaining 251.5 parts of 3-nitro-Ni (2-thienylmethyl) -2-pyridylamine with a top temperature of 100 ° C. following compounds: N-Al-Fluorophenylmethylamine with mp 76 ° C, N- (3-nitro-2-pyridinyl) -2-pyridylethylamine with mp 113.6 ° C, 4-methyl-N-yi and 2nitrophenyl (b) benzylamine, melting point 65 ° C, N - [, N-methylphenyl] -methyl] -3-niteo-2-aminopyridine, melting point 80.0-67.3 ° C, N- [M -fluorophenyl) -methyl} -3-mtro-4-pyridylamine melting point 136.8 ° C and 4-fluoro-N- (4-methyl-2-nitrophenyl] -benzylamine melting point 99.9 ° C. IV.To the cooled mixture of 40 parts of N- - [/ 4-fluoox) phenyfloAmethyl] -4-nitiro-3-pydynoanine in 1050 parts of trichloromethane is added dropwise. stirring at -10 ° C to 0 ° C 47 parts phosphorus pentachloride, then stirred and refluxed for 1 hour. Then, without interrupting the stirring, the mixture is cooled, the sediment, the meat, and the mixture with water are filtered off, alkalised with ammonium hydroxide and extracted with trichloromethane. The extract is dried, filtered, evaporated and the residue is mixed with diisopropyl ether, filtered off and dried to give 22.2 parts of N - {5-fluorophenyl) -methyl] -4-nitro-3-pyridylamine, m.p. 91. 9 ° C. Example 5 Mnetshanine 100 parts of N- [M-methoxyphenyl) -methyl] -3-mtro-2-pyridylamine, 3 parts of a 4% solution of thiophene in methanol and 480 parts of methanol saturated with ammonia hydrogenated under atmospheric pressure, at 50 ° C, in the presence of 5 parts of IOP / o palladium on charcoal. When the calculated amount of hydrogen is absorbed, the catalyst is drained off and the effluent evaporates, leaving 88.4 parts of N2 - [/ 4-methoxyphenyl) -methyl] -2,3-diaminopyridine, m.p. 118.1 ° C. The following compounds are prepared in an analogous manner: C, Nz- (2-thienylmethyl) -2,3-diaminopyridine, m.p. 92.1 ° C, N4 [(4-methylphenyl) methyl] -2,3-diam] inopyridine about temperature mp 125.1 ° C, N4 - [(4-fluorophenyl] -methyl] -3,4-diamLnopyridine mp 163.7 ° C and N8 - [4-fluorophenyl-Z-methido] -3,4-diaminopyridine mp 159.6 ° C Preparation of compounds of formula 1 Example W. To 73 parts of polyphosphoric acid at a temperature of 70 ° C, 2/7 of the amount of fewas lylumethyl methyl hydrochloride -4- ^ pr-zy9 145 710 l are added. As the temperature of the mixture rises to 100 ° C. Then 14 parts of 1,2-trinobenzene are added in portions, while stirring, and stirred at 170 ° C for 50 minutes, then the hot mixture is poured into 300 parts of warm water, and the acidic solution is calibrated. with potassium hydroxide solution, the free base formed is drained, washed with water and extracted with chloromethane. The residue is dried, evaporated and the solid residue recrystallized from a mixture of 2-propanone with methanol to give 17 parts of 2 [{iylphenylmethyl / -4-piperidinyl] - methyl] -1H-benziimidazole, mp 221.5-222 ° C (Compound No. 1). 2 - {[1- (1-phenylmethyl) -4-piperidinyl] -1H-limidazo [ 4,5-c] pyridine, m.p. 172.9 ° C (compound 2). Example VII. 27.3 parts of 1- (phenylmethyl) -4-piperidine ethanolimidanoate dihydrochloride and 14 parts of N- (2-furanylmethyl) dihydrochloride; overnight, then evaporated, added salt to the residue, and alkalinized with sodium carbonate and then extracted with 2-methylpentanone-2. The extract is dried, filtered, evaporated and the residue recrystallized from diethyl ether, filtered off and dried, yielding 15.5 parts (57%) 1- / 2-furanylmethyl / -2 - [[1- H; tphenylmethyl / -4-paiperidinyl] -methyl] -1H-benizimdidazole, m.p. 124.8 ° C (Compound No. 3). [1 - (Phenylmethyl) N -piperidinyl] -methyl] -H-benzimidazole, m.p. 141.0 ° C (No. 4) and 2 - [[1- (tphenylmethyl) -4-piperidinyl] -methyl ] -1-yB-pyridinylmethyl) -1H-benzimidazole, m.p. 125.4 ° C (# 5). Example VIII. 116.5 parts of O-ethyl (tphenylmethyl) -4-piperidinoethanimidate hydrochloride and 61.5 parts of NH./14- nethylphenylmethylstein-1.2-diamino-benzene in 400 parts of methanol are mixed and it is boiled under reflux overnight, then 40 parts of phenylmethylM-p-p-peridinimidate-O-ethyl hydrochloride are added and stirring is continued for 4 hours at the boiling point. The mixture is then evaporated, water and ammonium hydroxide are added to the residue, and the mixture is extracted with trichloromethane. The extract is dried, filtered, evaporated and the residue is fermented from acetoniltrile to 74.5 parts (63%) of 1- [/ 4- (methylphenyl) -imethyl] -2 - * [[1-iAphenylmethyl / -4 ° C piperidinyl] -methyl] -1H-benzimadazole, m.p. 124.2 ° C (No. N-phenylametyl (-4-pixeridinic)] -methyl] -1- (2-thienylmethyl) -H-benzimidazole, mp 156.3 ° C (No. 7), 3 - [(4-fluorophenyl) -methyl] - 2-i [(1-yiphenylmethyl) -4- 4-piperidinyl] H-methyl] -3H-ixn4-, m.p. 103.2-105.8aC (No. 8), 2- [(1-N-enylmethylMipiipOTidinyl} N-pyridinylmethyl (-3H-im'to mp 118.5-20.9 ° C (No. 0), 3 -. (12-furanyiomethyl) -2 - {, [ly (phennylylmethyl) -4-piperidinyl] - methyl] -3H-Himiidazo [4,5-to] pyridine, m.p. 118.5-1yl9.8 ° C (No. 10), 1- {y4-methoxyphenyl) -methyl} -24i [1- (phenylmethyl) - -4-piperidinyl] H-methyl] -1H-benzimlidazole o mp 95.2 ° C (No. 11), 2- [and [1- (Iphenylmethyl) i-4-piperidinyl] methyl] -3-2-10-ttenylmethyl) -3H-imidaio [4.5. ) pyridine, melting point. 115.2 ° C (inr 12), 3-yl] -methyl] -3H-imiidazo [4,5-b] pyridine (# 13), 1- (phenylmethyl) 2- [[1-yiphenylmethyl) -4- piperidin-15-methyl] -1'H-benzimdidazole, m.p. 1 ° C (No. 14), 3- [N 4 -methylphenyl] methyl] -24-piperidinyl] methyl] -3 H -imidazole [4 , 5-Jb] pyridine and (# 15), 3 - ([[4-methoxyphenyl [alpha] -methyl] -2- [and [li] phenylmethyl ([beta] -4-piperidinyl] H-methic] -3H-amidazo [4, 5-b] 1-pyridine, m.p. 83.4 ° C (No. 16), 1- [i (4-fluoro-phenyl? 4-methyl? ^ [[Lyiphenylmethyl) -4-pdperidinyl] -methyl] -1H-ibenzmiidazole 25 mp 112.6 ° C (No. 17), 1- (3-fairanylmethyl) [alpha] [and [1, ^ dynyl] H-methyl] -1H-benzimidazole mp 102.0 [deg.] C (# 18), 1- (3-fairanylmethyl). : [(4-fluorophenyl, '-methyl] -5-methyl-2- | [liiphenylmethyl) -4-piperidinyl] -methyl] -1H-benzimddazole 1H [M-fluoro (phenyl] -methyl] -6H-metexes -2-iD [1H / 1-phenylmethylM-piperidinyl] -methyl] -1H-benzidimidazole, m.p. 110 ° C (# 20), 5-fluoro-2 [and [1T (tphenylmethyl (1) -piperidinyl] -methyl] -1H -benzimidazole with a melting point of 206.2 ° C (No. 21) and 1- "[? 5-methyl-2-furanyl / H-methyl] -2- [[1W! phenylmethylM-piperidinyl] -methyl] -1H-ibenzimidazole with mp 96 ° C (No. 22). Example IX. 43 parts of 1-phenylmethyl / - -4-piperidine acetic acid hydrochloride, 31.5 parts of iN8 ^ [y4-fluorophenyl-lq /) - methyl] -2,3-pkyidine amdny, 850 parts of 45-phosphoryl chloride and 20 parts of N, N ^ The diethylphenylamine is stirred and boiled under reflux for 6 hours and then evaporated. The residue is treated twice with methylbenzene, evaporating each time, then the residue is poured into ice-water and made alkaline with dilute sodium hydroxide solution and then extracted with 2 portions of dichloromethane. The combined extracts are rinsed with water, dried, filtered, evaporated and the residue is purified by chromatography on a silica gel column using a mixture of trichloromethainol with methanol saturated with ammonia (95: 5 by volume) as eluent. The eluent was evaporated from the pure fractions and the residue recrystallized from acetonitrile to give 30 parts, (50.2%) 1- [(4-fluorophenyl) M-methyl] -2 - [{1- yl] -4- piperidinyl] -methyl] -1H-miidazo- [4,5-b} pyridine, m.p. 140.7 ° C (No. 23). -. [i [1-yiphenylmethyl) -4-11 145 710 12 iprijperidinio] -methyl] -1H- thaidiayl [4,5-c] pyridine m.p. 139.1 ° C (No. 24) and 3-i [ (4-fluoro-phenylyM] methyl-3H-ijniiidazoi [4,5-c} pkyd with a melting point of 116.0 ° C (No. 25). myself. Compounds of Formula I, as follows: 1- [74-Fluoro-phenyl-methyl] -2 - [{1-ytphenyl-ethyl] -1-piperidinyl] -methyl] -1H-beinziTndidazole, m.p. 127.9 ° C (No. 34 ), 2-C [1- (phenylethyl) -4-n-piperidinyl] methyl] -1- (4-thiazolylmethyl) -1H-benzimidazole, mp 98.3-105.4 ° C (No. 35); (2: 3) 1- [iM-Methiophenyl] -2- methylthyl] -2 - [-1- methyl-4Hp1 | peridinyl) -methyl] -IH-benzimidaaol, m.p. 1®9.2 ° C (No. 81 ), lj [i? 4-fluorophenesJicV'Hmethyl] -2 - [[1- (? 1-methylethylM-pi | peridinyl] -methyl] -1H-taidazo [4,5-c] pyridine, m.p. 116 ° C (inr 100), (1: 3) 3 - [2 -fluoro (phenyl / methyl] -2H [- 1 [2 -j®-pyridinyl] -ethyl] -4-piperidinyl [-methyl] -3 'oxalate H- -iimidazo [4,5-b] pyridine, m.p. 143 ° C (No. 101), (2: 5) 4n [4-it [4-it [1 ^ [^ - fluo-phenyfloykinetto] -1H-benzthi / midazoylMo-2 ] -meth ^^ bainone-2 melting at 162 ° C (No. 102), 1-, [i (4-fluorophenyl) -n-methyl] -2- [[1- [2- / 2Hpdryi Dynyl [beta] -ethyl] -4-n-piperidinyl] -phthyl] -1H] benzimidiaisole with a melting point of 138 ° C (No. mp 112.7 ° C (inr 106), 4n [1 - [i (4-fluoro-phenic) - ^^ -2] -methyl] -piperidineethainoyl-1, m.p. 136 ° C. (No. 107). (2: 5) 4 - [[1-4-thiazoQylmethyl) - 1H-beinzimddazoino-2] -methyl] -piperidine-1-ketanol, m.p. 1-23-137 ° C (No. 109) , (1: 2) 4 - {[γi4-methoxyphenyl-methyl] -1H- -benziinddazo-2] -methyl] -peridine ethanol oxalate, m.p. 149 ° C ((mr 110), (2: 3) fumarate 4- [{3- (2-pyridinylmethyl;, - 3 H -imidinyl-f4,5-b] pyridinyl-2] -inthio] H-piperidine ethanol--1, m.p. 150.7 ° C (no. Liii), 4- [ and [l-l-l-phenylmethyloy-lH-benzimthiidazolyl-2] -methyl] -pi) periditinoethainol-l, m.p. 137.3 ° C (No. 112), (1: 2) 4- [[[ 1 {i / 4-MethylphenylW-anethyl] -1H-benzoimidazolyl-2] -methyl] -piperidineethanol-1 with m.p. [3 - [4-Fluorophen (11H-methyl] -3H-nimMazoi [4,5-c} pyridinyloxy (2: 3) fumarate ] -piiperidinoethainol-1 melting point 145.1 ° C 4-j [[3 - [((4-fluoDX) phenyl] -methyl] -3H-imidaziQ [4,5-b] -pdxidinyl-2 ] -methyl] -piperidine-ethyl-1, m.p. 116.6 ° C (No. 115), 4 - [[1- [γi4-fluoro (phenyl)] -1H- oxalate (1: 2) -benzimen-dazo-2] -methyl-α - [(2- (nalftallelnylxByi), - -methio] -piperidineethainol-1 with a melting point of 153 ° C (No. 116), 3-thi4-dihydrochloride monohydrate Fluorophenyl) methyl] -2- [[In [2- (2H-thienyl) -ethyl] -4-piperidinyl] -imethyl] -3H-imidazo [4,5-b] pyridine, m.p. 210.5 ° C (No. 117), 1- [gamma] 4 -fluorophenyl) n-methyl oxalate hemihydrate (1: 2) -2- {and [li [2- [beta] 2-thienyl] -4 [beta] -pliperidinyl] -methyl -1H-benzimidazole, m.p. 141.7 ° C (# 118), (1: 2) 2 - [[1H [3- (4-fluoro-phenoxy] -propyl] -4-piperidinyl] -methio] - oxalate, ! - [M-fluorophenyl) -methylJ-1H-benzim iidazole melting at 186-1 ° C (# 119), 2- [i [1- [i [1VIH-benzimidazalyl-2-methylLoA-liH-ibenzimamideaollaJl-2] imethyl] -4-8iperidinyl] - methyl] -3- [Hr-yl-fluorophenyl-Z-imethyl] -3H-dimmiidazo [4,5-bipyridine, m.p. 247.3 ° C (# 138), 1- [3- [beta] oxalate 15 (1: 2) [j [ly [2-furanylmethyl] -1H-banquimidazolyl-2] -methyl] -1-piperidinyl] -propyl] -1,3-dihydro-2H-benzimidazionium-2, mp 214 ° C 218 ° C (# 139), 3- [H-yluorophen-20-lov-methyl] -2-j [[1- 2- n-3-yl] -3H-d-dimazo [4,5-b] - dihydrate monohydrate; pyridine, m.p. 167.4 ° C (# 142), 4-i [i [3-i [(4-fluorophenyl) methyl] -3H-imidazo [4,5-b] pL-ridinyl-2] n-methyl] -N- (1- {methylethyl) -1-piperidin-nopropionamide, m.p. 133.9 ° C (No. 143), (1: 2) 1-4f (4-fluotrophenyl) oxalate, -pi-D-phenyl and M- N-peridinylol-imethyl] -1H-benzimidazole, m.p. 120.3 ° C (No. 144), (2: 3) fumarain 4 - [[1- [N-4-fluoro (phenyl] -methyl] - 1H-benzimidaizoylyl o-'2J-methyl] -N- (1-methylethyl]-1-peptidinepropionamide, m.p. 138.0 ° C) (No. 145), (2: 3) 3- [i / 4-fluorine oxalate! LcHMmethyl ] -2- [and [1- [2- 35-phenyiosultaiyl] -ethyl] -4-piperidinyl] -tmethyl] -3H-imidazo [4,5-b] -pyridine, mp 159, 0 ° C (# 146) and (1: 2) 3 - {(4-fluorophenyl) methyl] -2 - [[1- [2-tphenyltoluene] -4-ipi | p ^^ 40 dazo [45-b] pyridine mp 199.6 ° C (# 147), ¦4-Jj [i3- [i / f4-fluorophenylZ-methyl] -3H-iimiidazo [4,5-b] pyridinyl -2] -methyl] -1-piperidinoacetamide, m.p. 1530 ° C (inr 148), 4 - {{1 - [(4-fluorphenyl) -2] -methyl] -1-piperidinoacetamide, m.p. 187 ° C (No. 149), 4h, [t [1-i [/ 4-fluorophenyl] -lLN-benzimidazolyl--2] -methyl} -N, N-dimethyl-a, a-diphenyl * - 1-pipe - 50 ridinobutyramide with a melting point of 151.1 ° C (No. 150), 6- [2- [4 - [[3- / E-furanylmethW-3H-iimidazo) [4,5-b] trihydrochloride monohydrate pyridinyl-2] methyl-1-piperidinyl o] -eth] o] -3,7-di 55lo) [3,2-a] pyrimflyindinone-5 with a melting point of 248.2I ° C (No. 151), (1: 2) oxalate 1- [ H-yluorophenyl and L -7) 4H-methoxyphenylc) and i-ethyl] -4-pilpe (ridinium] -methyl] -1H-imiida! ZQ [4,5-c] pyridine, mp 192.5 ° C (No. 202), (1: 1) 1- [&lt; 4-fluorophenyl & l-methyl] -2- {& [l- {2- - &lt; 4-methoxyphenyl] -ethyl] -4-pyipeidinyl] - oxalate methyl] -1H-imidazi-6 [4,5-b] pyridine, mp 176 ° C (# 203). "5 (1: 2) oxalic-3- [1 M-luorophenyl] -methyl] -2- {[-1 -145 710 1S 14-. [2- (4-methoxyphenyl] -ethyl] -pyridine, temp. melting point 191 ° C (nir 204), {1,2) 7- [2- [4- [[3- [4-fluonafeinyl] -nethyl] -3H-imidazio [4,5-b] pyridinyl oxalate -2 [alpha] -ethyl] -ll-.piipe (ridinyl] -ethyl ^ 3,4-diliydro-8-methyl) -hylOH2H, 6iHjpyrinido-! [2,1b] [1,3] tLazinone-6, m.p. 190 , 1 ° C (No. 205), 2 -, [, [1- {2V4-methoxyphenyl-ethyl] -piperidinium] -n-methyl] -1- (4-thiazolylmethyl) -lH-benzimydidazole dihydrochloride monohydrate, melting point 154-157 ° C (aur 245), 5-fluoro-l [beta] -fluoroenyl / H-methyl] -2- [[li [2- (4-methoxyphenyl] ethyl] -4H-piperidinyl] -methyl dihydrochloride dihydrate ] H1H-benzta, m.p. 102.3 ° C (inr. 277), 6-fluoro) 0-l [1-4-fluorophenyl] -methyl] -2-M-piperidinylmethyl MH-benzimidazole, m.p. 101 , O ° C (| No. 278), 4- [[3- [M-methylphenyl / n-methyl] -3H-imidazo [4,5-b] pyridinium-2] -methyl] -1-pliperidinoacetainitrile at a temperature of temperature 131.0 ° C (# 2T79), and (2: 3) N- [2- [4 [i [li [(I4-fluorophenyl] -methyl] -1H-benzimidazolyl-2] methyl] - fumarate 1-piperidinyl] - ethyl I-1H-berizimidazo-2-amine, m.p. 134yl ° C (# 326), N -, [2-i [4- [[3- [74-fluorophenyl] i- methyljo] -3H-phtaida! zo- [4-5-b] -pyridinyl-2] -methyl] -1-piperidinyl] -ethyl] -1H-benzdiimthijidazole-2-amino, mp 161.6 ° C (aur 329), (1: 3) N- [2- [4-0 [1- [H-yluonophenyl] -methyl] -1H-benzdiidazolyl-2] -methido-1-piperidimyl] - oxalate -ethyl] -thiazoyl ([5,4-blp-pyridine-2-mp. 147.8 ° C (No. 330), 2-i [{2- [4- [[1 - [b. lH-benizdmi-dazoyl-2] -methio] -1-piperidinio] -ethyl] -amino] -1H-p-drrimidinoin-4, m.p. 163.5 ° C (# 331), (1: 3) N- oxalate C2- {4-i [[1- [4-fluoroiphenyl] -methyl] ~ 1H-beinzimdidazioliIk) '- 2-methyl] -1-piperidinio] -2-ethyl] → azole [4,5-b] p (iD) dynoamdine-2, m.p. 187.4 ° C (No. 332), (2: 7) 4 - [[1 - [(4-fluorophenyl) oxalate ethyl] -1H- -benzoimidazolyl-2i] -methyllol-1,3-pyrimidinyl) - [1,4'-dupiperidinine I], m.p. 170.3 ° C (No. 347), (2: 6) N- oxalate [2 -, [4- [[1 -, [(4-fluorophenyl) methyl] -1H-dimidazo [4,5-to] pyridinyl-2i] methyl] -1-piperidinyl] ethyl] - 2-aminopyridines with a melting point of 173 ° C. (No. 348), 6-chloro-N4- [2- {4 - [[1- [(4-fluorophenyl-Z-methyl] -liH-benzimidazolyl- 2] - 4-methyl] -1-piperidinyl] ethyl] -4,5-diaminoipyridine ((# 350), (1: 2) N - [! 2'-i [4-i [[3-) W4 -fluorophenes W-methyl] -3H-dmiidaiso] [4,5-c] pyridimyiLo-2] -methyl] -1-p-pperidinyl] ethyl] -2-amino pyridine, m.p. 19 (2 ° C (inir 3 & 1 ), (1: 3) 4- [[3'-furanylmethido (3H-imiidazo [4,5-b] pyriditinyl-2] -methyl] -N- (2-thiazolyl) -1-pyridineethylamine oxalate mp 172.8 ° C (No. 352), N - [4 - [[3-i [M-fluioiX) phenyl] -methyl] -3H-imidazo [4- 5-c] pyridinyl oxalin -2] methyl] -1H-piperidinio] ethyl] -2-amiinopyrazine, m.p. 157 ° C (# 373), N- [2- [4 - [[ l-y4-phylorophenyl] -1H-barjzimdazolyl-2] -methytLo] -1-pdperidinyl] ethyl] -2-amiinopyridine, m.p. 1 & 5 ° C (# 374), (1: 1) N fumarate - [2-i [4- [y71-phenyl-1H-beinziimidaEolyl-2/1-methyl] -1-piperidinyl] -ethyl] -2-aminopyridine, m.p. 211 ° C (inr 375), (2: 3) N- [2- {4 - [[3 - [(4-fluoro-phenyl] -methyl] - &lt; 3 &gt; H-im! Ildazo [4,5-b] pyridinyl-2] -methyl] -1-piper- fumarate dyinyl] ethyl] -2-aimijnox) iiridine, m.p. 163 ° C (No. 376), in 4- [1 [(4-fluorophenyl] -methyl] -1H-benzimidazolyl-2] methyl] -N-) 1-Methyl-4-nitro-1H-imidaizolyl-5 / -1-piperidinoethylamine, m.p. 130.5 ° C (No. 377), 6-chloro-iN- [2 [4 - [[1- [M -fluorophenyl) - 'methyl] -1H-. 15 - * beriziimlidaizolyl-2] -methyli-1-pLperides: nyl] -ethyl] - -3-aminopyridazine, m.p. 175 ° C (No. 378), N- 1-oxide N- {2- [4 - [! [1 - [N-4-fluorofemol-methyl] -1H-benzimidazolyl-2] -methyl] -1-piperidinium] -ethyl] -ethyl-4-nitro-3-aminopyridine, m.p. 134.8 ° C (# 379) * 4- [¦ [1-iM4-fluorophenyW-methyl] -1H-beriziimidazolyl- -2] -methyl] -1'-t / 11-methyl-4nr RN -5] - [1,4 '- 143.7 ° C (inr 380), 25 4-chloro ^ N - ([2 ^ [4 -! [[1 - [/ 4-fluoro-phenylo; -methyl] -1H-ibeinimidazolyl ^ 2] -methyl ] -1-piperidinyl] -ethyl] -1-amiinonaphthailazyine, m.p. 169 ° C Jnr 38H, (1: 2) 4-ohloro-N- [2 - ([4 - [[1 - ([/ 4) -fluorophenyl-methyl], 1H-ben-dimidaizolyl-2] -methyl] -1-piperidinyl] -ethyl] -6-methyl-2-hamilr, mp 165 ° C (No. 382) , 2-chloro-N- [2-i [44 [1 - {/ 4-: 4-methyl] 1-piperidinyl] ethyl] - 35 -6-methyl-4-aninopyridine melting ¬nia 14! 2.90C (No. 383), (2: 5) 6-c oxalate; chloro-Ni [2-iI4- [and [1- { [4-Fluorophenyl] -1-methyl] -1H-ben-imidazolyl-2] -methyl] -1-pyridinyl] -ethyl] -4-aaT-dnopyridine, m.p. 174 ° C (No. 384), ' (2: 5) 3- [2- [4-i [i [1- [γ4-fluoro-phenyl / - 'methyl-] -1Hn-benzimidazoMlo-2] -methyl] -1-piperidinio] -ethio] -ocBazolidinone oxalate -2 with a melting point of 147.6 ° C (No. 385), «(1: 2) oxalate 2- [and [i2- [4 - [[1- [yl4-fluoro-phenyl] -1 / '-methyl] -1H- benzimidazoM1-7-ethylptol] -thiazolo [5,4-b] pyridine, m.p. 198.7 [deg.] C (# 387), 2 [deg.] D [2- [4 [beta] [[1- ([?] -fluorophenyl) -methyl] -1H-benzimi- * ° dazolyl-2] trimethyl] -1-piperidinyl] ethyl] -thio] -thiazol [4,5-c] -, pyridine, m.p. 12-12.80C (No. 388), (1: 2). 4-t [3- [γ? 4-Fluoropheinyl) -methyl] -3H- -liimMazO [4i, 5-b] ipyridinyl-t2i] -methyl] -N4- 2-pyrim-55dynyi / -1-piperidinoacetamMu with a melting point of 160.4 ° C (No. 389), (1: 3) 1- [(4-phyliorophenyl) oxalate] -2- [[1- - [2- [2- [2- and 12-pyrimidinyloxy] -ethyl] - oxalate 4-pdoc) eryidinyl] -methyl] -1H-benzdimidazole, mp 60-161 ° C (No. 301), monohydrate (1: 2) of 11 # J-furanylmethyl / -2 - oxalate ([and [ 1- [2-i / i2-pyrimidinylox ^ -ethyl] -4-pii) eryidinyl] -methyl] -1H-benzthalidazole m.p. 1790C (No. 392), &quot; 3-y4-fluorophenyl / methyl trihydrochloride ] -2 - ([1-145'15-methyl] -3H-dmd) diazo [4,5-'b] p-diiridine, m.p. 129.5 ° C (# 394), (1: 3) N- fumarate [2- {4 - ([[[1- [i &lt; 4-ffluiOiroiphenyl] -me (thiyl] -1H-ben ™ n -Mazolyl-2] -methyl] &lt; 1 &gt; (iaEo [4,5-c] -! ^^ with a melting point of 184 ° C (inr 415), (1: 3) fumarate N- [2 [4 - [[1- (2-thienyl) - 1H- 1benzaimiidazoylfflo-2] -1H-iiMdai → [4,5-c] pyriditinoamine-2 in the form of one M novodyna with a melting point of 198 ° C (No. 416), (1: 3) N- [2-i [4H [[3- i / 12-furainyCLo'methyl] -3H- -irriidazo [4,5-b ] -pyrin-dynyl] -ethyl] -1H-imidazo [4,5-c] pyridin-γ ^^ as monohydrate, m.p. 174.1PC (No. 417), (1: 4) Ni [2- oxalate [4H [i [ly ^ -fuirainyiLoimethyl] -1H- -benztaidazofldlo ^] -1-piperidymyio] ^ ethyl] -1Hnim-dazo [4-5 ^ c] pyridinamine-12 with a melting point of 200.8 ° C (No. 418), <(1: 4) N- [2-i [4 - [[3-i (E-pyridinylmethyl] -43Hnimidazo [4-5-'b] pyridinyl-i2i] H-methyl] -1- piijeiry- oxalate dyoyl] -ethyl] -1H4-mid) azo ([4,5] plixidinium-2 m.p. 189.2 ° C (No. 419), 25 (2: 5) N- [2-i [4- [[3- (2-thenienytamethyl) L3H- -imikiazoi [4,5-b] pyridimyl-2] -imethio] -1-pi | peridinine Qo] t-yl] -1H4imddazo [4.5 ^] pdridinD5Bnin-2 with a melting point of 154 ° C (or 420), (Jl: 3) N42- [4 - {[1-M4-methylphenyl] -methyl] -1H-benzlimQdazoyliiiLo-2] -methyl] -1-pLperidine oxalate - Io] -ethyl] -1H-imddazo [4,5] - pyridiniumimphyln y-2 with a melting point of 2103 ° C (inr 421), (1: 4) N- [2- [4 ^ [{1-yephaylmethyl) -1H-bendrraidaizolyl-2] -methyl] -lipiperidinyl] - oxalate ethyl] -1H-35-imidazo [4,5-c] paridinamine-2 with a melting point of 199 ° PC (No. 422), (1: 5) oxalate N- [2 → [4 - * [[3 ° C) [i (4H-methyl (phenyl] -inetyl-3Hnimidazo [4,5-c] p-pyridiyl-2] n-methyl] -1-piperydimyl] -1-yl-1H-imddazo [4,5-c} p &lt; 4 &gt; melting point 150.5 ° C (mr 423), (2: 5) N- [2-i [4 - [[3 - [/ 4-fkioaxxfenyik / -methyl-3Hnym! daza [4.5- cJpyridine - rydymy! o] -ethyl] -ilH-tinnddazo [4,5-c] and &lt; + &gt; 3 - [(4-fluoro-phenyl) -methyl] -3H-dlmidaiso [4,5-b] pyridine] o-2] - (methyl] -1-piperidinyl] ethyl] -2H-pyridinomethylamine, mp 160.3 ^ 0 ^ No. 426), 4-i [[1- [i (14-fluo-phenyl] -ffnetic] -1Hnberizttmdjdazolyl-50-2] -methyl] -N- emylmethyl, and -ilnpdperidineethylamine ( No. 426), (1: 2) N- [2- [4 -, [[1- [M-fluorophenesW- ^ -1H-benzoyl-miclazolyl-2J-methyl o] -1-ptopyridinyl] -ethyl] -2-p-diidinimethyamine, m.p. 144.7 ° C (mr 427), (1: 2) N- [2- [4 - [[1- [i / ) 4-fluorophenylethyl] -1H- benzinniiiclazoldl-2] -1-priperidinyl] ethyl] -N-methylphthaane urea, m.p. 169.4 ° C (#428), 60 (1: 2) florasamide oxalate N - {[2- [4-i [[1- {yi4-fluorofemyl) -methylJ-1H-bemztinn-piperidinyl] - ethyl] -tkxfeaicarboxy], m.p. 177.4 ° C (inr 43i), acidamide N- [2N [4 - [[3- [and (4-fluoro-phenyl] - (methyl] - 65 L) * -3H-imddazo [4,5-c] pyridinyl] -meityl] -1-piperidinyl] -ethyl] -fyrancarboxylic ^ 3, m.p., 139.3 ° C (No. 432), <2: 5) N- [2- [4 - [[1 - [(4-fluoro-phenyl] -methyl] -1H-beristhimidazolyl-2] -methyl] -1-piperidinyl] -ethyl] -1-imethio acid amide oxalate -1 H-picolocarboxy-2 with a melting point of 164.5 ° C (No. 433), N- [2- [4- - [[il- i [i / 4- fLuorophenyl and Z-methyl] -IH-benzimidazoldl -2] anethio] -1-piperidinyl] -ethyl] -furylcarboxylic-3 with a melting point of 139.7 ° C (No. 434), (1: 3) acid amide oxalate [2 - ([4 ^ [[3- [M-fluoro-phenyl] -methyl] -3H-imidazo [4,5-b] pyridinyl-2] -methyl] -1-piperidinyl] ethyl] - pyrimidimecarboxylate-3 with m.p. Temperature 149 ° C (No. 435), (1: 2) 3-Amimidazolyl-Ni [2 ^, [4-i [[1- [/ 14-fluorophenyl] -1H-benzimidazolyl-2] amide oxalate] - -methyl] -1-piperidinyl] -ethyl] -pyrazinecarboxyl-2, m.p. 166.3 ° C (# 436), (1: 2) Ni [2 &lt; 2 &gt; and [4- [and [ ln [γ-4-fluoro-phanyflo] -methyl] -1H-benzaimidazolyl-S] -onethyl] -1-pdperidyl] -ethyl] -thiazolecarboxylic acid-4, m.p. 167.8 ° C (No. 437), (2: 5) Ni [2-i [4 - ([[1 - [(4-fluorophenyl-Z-imethyl] -1H-benzimidazolyl-2] -1-piperidinyl] -ethyl] -2-methoxypyridine-3-carboxylic acid amide oxalate) mp 182.2 ° C id 438), (1: 2) N- [2 - [[4 - [[11 [i] 4-fluoro-phenyl] -1H-benzlimffidazolal-2] -methyl] -1 oxalate -pdperidine-io] -ethyl] -y-keto-2-tolopheneacetamlidia, m.p. 180 ° C (No. 439), (2: 5) N4 oxalate [2- [4-i [[1 - '[/ 4-fluorophenyl) methyl] -1H-ibenzimidazolyl-2] methyl] -1-piperidinyl] ethyl] -3-thiopheneacetamide, m.p. 185 ° C (No. 440), (1: 2)oxalam N -, [2-i [4- [i [il- {i (14-fluorophenyl) -me; tyl-] -1H4-dimazolyl-2] -methyl] -1-pliperidin-3-yl] -2- meth-kisy-5-l-keto-butyl-benzamide, m.p. 161 ° C (No. 441), acid amide N- [2- [4] [and [1- [and (4-fluorophenyl) -methyl] -1H-benzimmdazolyl-2] H-methyl] -1-piperidinyl] ethyl] -1-methyl-1H-indole-2-carboxylic acid, m.p. 136.9 ° C (No. 442), and (1: 2) oxalate N- [2H [4- [Il- [γ4-fluoro-femyl] -1-piperidinyl] -ethyl] -thiophenecarboxylic acid amide ^ 2, m.p. 157 ° C (No. 443), acid amide N- {2- {4- [[1- (4-fluorophenyl) N-methyl] -1H-benzimidazolyl-1,2] Hmethyl] -1- [beta] -peridinyl] -ethyl] -4-hydroxycMnc. chase temperature 262 ° C (No. 444), acid amide N- {2-i [4 - [[1- [i (14-fluorophenyl) n-methyl] -1H-benzlimildazole ^ ^ methyl-2 ^ ke1x N- [2- [4 - [[i (4-fluoro-phenyl) -methio] -1H- benziimiidiazoilyl-2] n methyl] -1-pi-1-peridinyl] -ethyl] -thiazoio (kaanbokisyl-2, m.p. 177.15 °; C (No. 446X, monohydrate (1: 3) acid amtide oxalate and N - / [ 2- - [4- [and [1H [(4-fluoaxphenyl) Hmethyl] -1H-! Be! N-dimazolyl-2] -methyl] -1- (piperidine11o] ethyl] piperidine- (17-carboxylic-4) mp 164 ° C (mir 447), (2: 5) N '- [2- [4-f [i [3- {i (4-fluoroenyl) methyl] -3H-ilniidaEo oxalate [4,5-b] pdridinyl-2} -m-ridinyl] -ethyl] -N, 4, N, ethytar, melting point 93.8 ° C (rr. 448), N- [2- [4- [[ 1- [(4 -fluiorophenyl) anethyl] -1H-benzamidazolyl-2] -methyl] -1-piperidinyl] -eth- ^^nic (nor 449), 4- [and fumarate monohydrate (1: 2) [li [/ 4-fluoro-phenylMethyl] -1H-bansimiiidazoyl-2] -methyl] -N- (1-methyl-1H-knidazol'Llo-2 / -1-piperidine ethylamine with a topndend temperature of U9.2 ° C (No. 452 ), (1: 2) 4- [[1 - [/ 4-FluorophenylZ-methyl] -1H- -benzimidazoMo-2] -methyl-N- (11HH1, ^^ -piperidineethylaniline oxalate in the form of an ioohydrate, m.p. 126.7 ° C (No. 4 63), 4 -; [[1- [i) -H-fluorophenylZ-methyl] -1H-ibenzoimidazolyl-12] -methyl] -N-iM-phenyl-2-thiazoiloyl / 1-l-piperidine-ethylamine at mp 122 ° C (# 454), 2 - {[2 - [- 4- - [: [1 - {(4-fluoroolenyl) / Mira ^ -2] -methyl] acid ethyl ester oxalate (1: 2) -! - piperidine] o] -ethyl] -amtoo] -tdi E of the 4-tetra-carboxylic acid m.p. 179 ° C (# 455), oxalate (2: 7) 4 - [[1 - [? 4-fluoro ( phenyl (N-benzoyl-2-methyl-2) -1-piperidinoethirin, m.p. 148 ° C. (No. 456), (2: 5) 1 - [N-fluoax) oxalate (phenyl) -! methyl] -2 - [[1- [2- (2-methyl-4-it-Qazolyl) -ethyl] -4-piperidinyl] -methyl] -1H-benEiimi'dazole, m.p. 123.5 ° C ( No. 459), 3- {2- [4 - {[1- < [2 &gt; Fluorophenyl!] -methyl] -1H-benzidimijidazolyl-2] -methyl] -1-paperidinyl] ethyl] -2y3- dihydro-2-thdoketo-1H-quinazolone-4 with a melting point of 218.6 ° C (No. 460), 2-amino-N- [2- [4-t [[1- / 2-fuananyl) ethyl (-1H-bein! zi ^ midazoMo-2] n-methyl] -1-piperidinyl] -ethyl] -benzamide, mp. ieinda 125 ° C (# 466), N- [2- {4 - [[1- (4-fluorophenyl] methyl] -1H-toemiimddaazolyl-2] -methyl] -1-piperidinyl] -ethyl] -2 -ttaethyl-amino-benzimide, m.p. B4 ° C (No. 467), 2-amino-N- [2- {4 - [[1- [1- [4- phylliorophenyl] -methyl] -1H-benziimidazolyl-2] -methyl] -1-paperidinyl] ethyl] benzamide, m.p. 130.1 ° C (# 468), (2: 6) N- [2- [4- [3- [i / 4-fluorophenyl] oxalate N-methyl] - - 3 H -himidazo [4,5-b] pyridinyl-2] n-methyl] -1-piperidinium] -ethyl] -2- (methylanino) -benzaimide, melting point 172 ° C (No. 470) , 2-amino-N- [4- [4H [[l-,] 2-furanytanethyl) -1H-benzimidazolyl-2] methyl] -1-piperidinyl] butyl] benzamide, m.p. - 127.2 ° C (# 472), 2-aimdino 4 Nf [1 2- [4- [[3- (2-furanylmethyl), - 3HHimi (da- zo [4,5-b] pyridinyl- 2] -methyl] -1-piperidinyl] -ethyl-ethylbenzasmide, m.p. 136.9 ° C (# 473), N- [2- [4H [and [3 N (2Hf'ur-, pyridinyl-2] H-methyl] -1 -pflperidinyl] ethyl] -2- (methylamino-Z-benzamide, m.p. 81 ° C (No. 474), oxalate (1: 2) 2-Amino-N- [2- [4- {and [3-t (4-fluoro-phen-15 710 18-l-methyl-3H-imodazo [4,5-c] pyridite) - 2] n-methyl] -1-p-p-peridinyl] -ethic] -banan amidium. mp. 101 ° C (# 477), 2-amlinO-N- [2T {4-i [i [1- (2-thienyl) 5-idazolillo-2] -methyl] -! - piperidinyl] -1-ethyl] ibenzimide at mp 143 ° C (# 478), oxalate (1: 1) α, 3-dyiydflX-A2H-dimethylOM-3 - '[2- {4- - [and [3 N-pyridine] omeltyllo-3-methyl-2] -methyl- 1H-piperidinyl] -ethyl] -1H-quinazo-fcon-4 melting at 209.7 ° C (1: 1) 3- {2- [4-i]) [ln [(4-fluorophenyd) -tmethyl] -1H-benzdmtidaizolyl-2] -methyl] -1-piperidinyl] -Hetyl] -2-methyl-3 "HK3Mnaau3dtnon-4" melting point 210 ° C (No. 481), 3- [2- {4 trihydrate dihydrate) - [[1- (2-tfuranylmethyl] -1H-benzdimiidaisoldflo-4-methyl] -1-pdperidinflo] Hetyl] -2-methyl-3H ^^ with a melting point of 219 ° C (No. 482); 3h [2- [4 - [[3 - [/ 4-: fluoro E enyao ^^ 20 [4,5-b] -pdxyidinyl-a] -methyl] -1-thi | peridinyl] -ethyl] -2 -Methyl &lt; 1 &gt; H-chtinazc # n © n-4 at 147 ° C (# 483), iumarate (1: 3) 3- [2 &lt; [4- [f3-] 2-furanylmethyl (x / -3H -iimi- dazo [4,5-b] -β-yidinyl-2] H-methyl] -1-piJ) eryidine] o] - 25-ethyl ] -2-methyl-3H-hydroxy, melting point 183.7 ° C 3- [2- [4 - {[34-tethe Hruiia (nylin-4-pyridinyl-2] -methylsil-p-p-peridinyl] -ethyl] - 2,3- -d'-ydrc ^ 1-4nety-2-thiokecMH-c ^ with 30 mp 168 ° C 3- [2- [4- [[1- [. ] -1H-benzimidazolyl-2] -methyl] -1-piperidinyl] -1-diix-1-Triethio-2H-2H-2 HCl-2 HCl 147 ° C (No. 407), 35 3 [2- [4- [ LM ^ lu) orophenyiD / H ^ -pyridinyl-2] n-methyl] -1-piperidinite] -ethyl] -2,3-dihydro-1- mp 178.7 ° C (No. 488), 3- [4 - [4 - [{1- [B 4-fluorophenylMethyl] -1H-benfflimQda- 40 zoMo-2] 4-methyl] -1-p-p-peridinyl] -butic)] -1H, 3H-cnanaiaophosphino-2,4 melting point 187 ° C (tir 489), 3- [4- [4 - [{1- [beta] -furanylmethyl-1H-2] -methyl] -1-piperidinyl] -baitfo-45 zolinolione-2,4, melting point ISS ,! ^ (No.490), -. 3 R [2- [4] and [[3- (2-furanylmethyl) -3H-imidase [1-pyridinyl-2] -methyl] -1-ptiperidin-2 -dinidiy-2 * t4oketo-1HK5hQtnCaolirio; riu-4 o m.p. 191.7 ° C (# 492), 1t [2- [4- [and [1-J 5 M 2 uorophen 5 H 2 H 2 • zolyl-2] -methyl] -1-, piperidinyl] ethyl] -1,3-di-di-2H-benzimidiazolole-3H 2, m.p. 157.6 ° C (No. 493), 1H-benzimidazoflyl- [alpha]] -methyl] -1-piperid, ynyl] -ethyl] -9H-pur, nol-8, m.p. 242.8 ° C (# 494), 9_ [2- [4- < [[1 - [(4-fluoro-phenyl) -H-methyl] -1H-benzimoyl-2] H-methyl] -1-piperidinyl] -ethyl-9H-purine-8-ol with a melting point of 163 ° C (No. 495), 3-i [2- [4-iH3'-furanylmethyl) -3HHimAdaop [4,5-b] -pyridinyl-2] -methyl] -1-piperidinyl] ethyl] -6-methylthylene [2,3 -d] pyrimidine-1H, 3H- * dien-2,4- mp. 136 ° C (No. 496), 19 145 710 20 oxalate (1: 2) 3- [2- [4 - [[1- y4-fluoro (nyl) -imiethyl] -1H-benzinilidazolyl-2] -methyl] -1-piperidinyl] -ethyl] -6,7,8,9-tetrahydrate ro-2-non-ethyl-4H-pyrido [1,2-ai] pyrimidinone-4 m.p. 192 ° C (No. Ni [2- [4- / 4-fluorophenylZ-methyl] -1H-benimidazomo oxalate -2] -methyl! O] -1- [beta] (iiiperidinyl] -ethyl] -2-pyridine Thioiaimdine melting at 156.7 ° C (# 499), N- [2h [2h [4- [1.1 - [(4-fluorofemyLoZ-methyl] -1H-benzriimidazo] Jik-2] -methyl] -1-pd-peridinyl] -ethyl-0] -3-, pyridazineimine, m.p. 197.3 ° C (# 500), N- [2 -, [4- [[1- [i] -4-fluorophenylmethyl] -1H-benzdmiidia-2] -methyl] -1-pyridinyl] -ie (yl] -4-pyridinoamine melting point. 60 ° C (: # 501), 9- [2H [4 - [[1 - {(4-fluoro-phene, N-4-zol-2] -methyl] -yl-p-p-steridinyl] -ethyl] -9H-pyryol-8 with a melting point of 213.1 ° C N4- [2- [4 - [[1- [(4) arophenyl] -1H-beaiz.i! md-idazoMlo-2] -methyl] -1-piperidinyl] - ethyl] -4,5-pdridinedineimdne (# 503), 4-1 [2 ^ [4- [[1- [N-4-fluorophenyl-Z-methyl] -1H-benzimidazoMo-2] -methyl] -1 -pipeiry] Hetyl] -phenol, m.p. 130 ° C (inr 504), N1- [2- [4- [[1- [?] -fluorophenyl / H-methyl] -1H-benairnd-dazolyl-2] methyl] -1-piperidinyl] ethyl] -1,2-diamainobanzene (No. 506), 9_ [2- {4- [[1- [B-fluorophenyl] -methyl] -1H-beinzdmidazol (lo-2 ] -methyl] -1-piperidinyl] -thio (-9H-purine, m.p. 133.5 ° C (inr 507), N- [2- [4- [[1- [t) 4-fluoro-phenyl Z- methyl] -1H-benzamidizoMlo-1-methylol-1-p-piperidinyl-ethanol-N-yS-pyriminyl-N-yS-pyriminyl W-benzamide, mp 108.4 ° C (No. 508), oxalate (1: 2) N- [ 2 -. [4 ^ [i [1- [(4-fluorophenyl] -methyl] -1H-benziimddazolyl-2-methyl] -1-c-thiiperidinyl] -ethyl] -iN- (2-ip) drimdidinyl] -a) oeitimide, m.p. 173.2 ° C (No. 510), 1: 5) 2-McetylmethylcNaiminoi (-N-, [2-1 [4-1 [[| 1- - / 2) -furanylmethyl) -1H-benizimidaiZ'Oifly-2] -methyl] -1-piperidinyl] -ethyl] -benzamdidium at thioindium temperature 146.3 ° C (inr 511), N- [2- [4- [[ i (4-fluorophenesWH-methyl] -1H-befllJZliIrIlttllazo-l! yl-2] -methylJO] -1-piperidinyl] -ethyl] -N-methyl-2-aminopyridine with a melting point of 135 ° C (No. 514), 1 - and [(2-fluorophenyl) methyl] -2- [t [1- [2 N (4-methoxyphenyl) -ethyl] -4-piperidinyl] -methyl] -1H-benizimidazole, m.p. 109 ° C (mr 515) , 2- [and [1- [2V4-Methokisyiphenyl] -ethyl-ethyl] -4-piperidinyl] -methyl] -1- (2-phenylethyl) -H-benis Amidaziol monohydrate in the form of the monohydrate of temperature tqpnieiniiIa 175.6 ° C (No. 516), (2: 5) 1- (diphenylkymethyl) -2l- [and [1- [2-; methyl] -1H-benzimidaziol, m.p. 174.5 ° C '(No. 517), and [A5, dimethylphene, nyl] - imethyl] -2- [[1- [2-i / 4-methoxyphenyl] Z-ethyl] -4-pyridinyl] methyl] -1H-benzimidazole mp. 118 ° C (No. 518), 1- {N, 2,6-di-chlorofemyl-Z-methyl] -2- [[1- [2-metho-xyphemyl-Z-ethyl] -4-piperidinyl] -methyl] -1H-benzylmidazole, m.p. 152 ° C (inr 519), 1 - [(3-c (chloropheinyl) -methyl] -2- - [[1- [2- (4-methoxyphenyl) -ethyl] -4-piperidinyl] -1-methyl] -1H-beri-2imidazoyl dihydrochloride melting point 173 ° C (No. 520), chiaaviate (2: 5) 2 - [[1- [2-4-methoic] syphenyl] -ethyl] -4-pyridinyl] n-methyl] -1- / l -naphthalenylmethyl) -1H-banziimidaisooyl, m.p. 186.3 ° C (inr 5211), 1-eyclohexyl-2 [[1- [2- [2- (4-methoxyphemyl) -ethyl] -4-piperidimyl] - dihydrochloride methyl] -1H-bemimidiaisole in the form of the monohydrate with a melting point of 189.2 ° C (inr 5 (22), oxalate (1: 2) 2 - [[1- [2- and (4-methoxyphenyl) - ethyl] -4-npiperidinio] -methyl] -1- (3-tdenylmethyl) -1H-Jbenzimidazole, m.p. 185 ° C (No. 523), fumarate (1: 1) 2 - [[1- [2- (4-methoxyphenyl) -ethyl] -4-pipephenyl] -methyl] -1,4-pyrazinylmethyl) -1,4-benzimidiaisole, m.p. 180. 1 ° C (inir 524), oxalate <1: 2) 2 - [[1- [2 N (14-methoxyphenyl) ethyl] -4-piperidinyl] methyl] -1- [, N 5-methyl- 2-thiienyl) -methylJ-1H-beniziimidaole, m.p. 194.4 ° CJ (# 525), oxalate (1: 2) 2 - {[1- [2- (4-methoxyphenyl) - ethyl] -4-6-piperidinyl] -methyl] -1- [and (3H-methylk2-thienyl) -methyl] -1H-benzimidazole as monohydrate, m.p. 1G6.8 ° C (No. 526). described in the following examples are also producing compounds of formula I1, in which L, R1 and A1 have the excerpts given in Table 1. This table also lists the mumbers of the compounds produced and their melting points and indicates whether the compound obtained in the form of the free base or acid salt, wherein: x is fumaric acid salt (2: 3), x x is soybean monohydrate with oxalic acid (1: 2) and xxx is acid salt with s (1: 2) Number (compound 1 L 2 Table 1 Ri 3 Ai 4 Form 5 Melting point ° C 6 82 83 86 87 88 39 CHS ^ CHs / aCH CH3 / CH, / 2CH CHS / CH ^ CIJ 4- F-CftH4CH2 4-F-CeH4CH2 2-furainylmethyl 2-furanylmethyl1 4-thiazoldylmethyl 4-F-C6H4CH2 CH CH CH CH CH NXXX HCl XX xxx 193.4 165.3 178 206.5 146.7 163.621 145 710 22 continued table 1 6 90 9! 92 93 94 95 CH, CH ^ -FC ^ H ^ aCE / CH ^ CH $ / CH5 / 2CH, Oty2CH 4-F-C6H4CH2 HH CqH. ^ CH.2 CgH ^ CH2 CH3 N CH CH CH CH CH XX base xxx base xxx xxx 158.8 oil 212 96.6 193.8 1116.9 The compounds of formula I8, in which I /, is, R1 and A1 have the meaning given in table 2, are also prepared in an analogous manner. this also provides information on the obtained compounds, as in table 1. Table 2 Number / relation 1 120 121 122 123 124 125 126 127 128 129 130 131 1 (32 133 134 135 136 137 2 C6H $ 0- 4-F-C6H4 C * H5- formula 8 4-monphioliinyl formula 8 C2H0O- 4-F-C6H4CyO / - / CH ^ CHNHO / O / - C6HsS- C6HgSG2- 4HmorpholIinyl 1H-benziimidiazoMo-2 C2HgO- / CH9 / 2CHNHOO / - 440 - 1H-bemaiimiidiazolyl-2 2,3Hdijhy (Lro-1,4-4-benzodiioxinyl-2s 3 2 3 2 2 2 2 2 3 1 2 2 2 1 2 1 3 1 1 R1 4 HHH 4-F ^ CtfH4-CH2 4 -F-C6H4CH2 4-F-C6H ^ CH2 4 F-CGH4CH2 4-F-CeH4CH2 4-FhC6H4CH2 4-F-C6H4CH2 4-F-C8H4CH2 4-F-C6H4CH2 4-F-C6H4CH2 4-F-C6H4CH2 4- F-C6H4CH2 4-F-C6H4CH2 4-FC "H4CH2 4-F-CftH4CH2 A1 5 CH CH CH CH NNNNN CH CH CH N CH CH NC HN form 6 rule the rule is 2JGOOHA Z / COOBk ayoooH / 2 aHci H20 2HC1 HsO JCOOHJ2 2 / OOOH / 2 2JCOOW2 X 3iy1COOH / 2 xxx xxx 2 (/ COOH / 2 XX 2JVOOW2 Pyrodutot melting point, ° C 7 142-444 141 ^ 143 182 ^ 186 1B7.3 205.7 182.6 180.5 167.8 227.1 173.9 198.4 207.1 165.3 113.4 151.8 157.5 205.5 176.2 ^ The compounds of formula I8 are also prepared in an analogous manner, in which I /, s, R1a and A1 have the meaning given in Table 3. The properties of the compounds obtained are given as in Table 1, the salts are denoted as follows: x is the monohydrate of the salt with the acid fumaric acid (2: 3), xx is fumaric acid salt (2: 3) and xxx is fumaric acid salt (1: 2). Compound number 1 1/2 s 3 R! "a 4 Table 3 Ai 5 Ptroduct form 6 itopndeniai temperature, ° C 7 152 153 1154 155 156 157 168 formula 9 formula 9 formula 9 formula 9 formula 10 formula 11 3 3 3 3 3 3 2 2-furanyl- 4-F-C6H4- 4-CHsO-C6H4 - C0H5- C6H5- 4-F-C6H4- 4-FN CH CH CH N CH CH 1.5 / COOH ^ X XX ^ / COOHi ^ 3 / OQH / 2base xxx 266 132.2 1168.2 011.8 147 186.923 145 710 24 cont. table 3 6 159 160 161 162 163 164 165 I166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 r 184 186 187 pattern 10 pattern 12 pattern 13 pattern 14 pattern 14 pattern 15 pattern 13 pattern 11 pattern 14 pattern 14 pattern 10 pattern 16 pattern 10 pattern 10 pattern 12 pattern 13 pattern 15 pattern 17 pattern 18 pattern 11 pattern 16 pattern 18 pattern 19 pattern 20 pattern 21 pattern 22 pattern 10 pattern 10 3 2 2 2 2 2 2 2 2 2 3 2 2 3 2 2 2 2 2 2 2 2 2 2 1 1 2 2 2-funainyl- 4-F-C6H4- 4-F-C6H4- 4-F-CftH4- 2-fuirainyL 4-F-C6H4- 2-furanyl - 2-fiurainyl- 2-furanyl- 2-futranyl- 2-furanyl- 2-furainyl 2i-furainyl 4-F-C6H4- 2-furanyl 2-furanyl- 2-fuirainyl- 2-furajnyl- 4-F-C6H4- 2-fuirainyl- 4-F-C6H4- 2-furainyl- 4-F-C6H4- 4-F-C6H4- 4-F-C6H4- 4-F-C6H4- 2-taenyl- 4-thiazolyl- CH base CH xx CH xxx CH xx CH 2i / COCW2 2H2C CH sits CH 2HC1.2H20 CH 3HC1.2H20 CH 3HC1.2H20 N 3HC1 • H20 N sits N 2HC1, H20 N base N base N 3HC1.2H20 N 2HC1.H20 CH base N 2HCLH20 N 3 HCl 2 H 2 O N xxx N 2 H 1 H 2 O N 2.5 (COOCH / 2-H 2 O CH 3 O 2. / COOFL / s CH base CH base CH 3, → 00 → CH base CH base 179.5 104.4 174.1 186.2 164 168.3 240.7 197 215.1 250 198.8 227.9 199.6 133 186.2 decomposition 204.7 decomposition 175.4 182 | , 7 229.2 183.9 240.5 163.7 161.6 101.8 164.7 161.0 103.9 211.0 The compounds of formula I4 are also prepared in an analogous manner, where I /, s, R1a and A1 are significantly listed in Table 4. In this table, the symbol x represents CaH ^ -CH- ^ -FC ^ H ^ -CH- / ^ - F-CfiH ^ -CH- / 4-F-C6H4 / 2CH- / 4-F-C6H4 / 2-CH / 4-F-C6H4 / 2-CH 4-CHsO-C6H4- 2i, 3 ^ diihydrio- 1,4-benzodioJxynyl-2 C2H50-C / = OA s 2 2 3 3 3 3 3 3 2 1 1 R1 "3 2-furainyl- 4 -CH3OC6H4- 2l-iuirainyl- 2-pyridinyl 4-CHsO-C6H4- 4-F ^ C6H4- CeH5- CeH5- CeH5- C6H5- 4-F-C6H4- A * N CH NN CH N CH HN CH CH Product form WOOH / j xx z / OOOH / 2 2 ^ COOH ^ 2, / CObH ^ 2 / COOH / 2 2.5,1COOH ^ 2, € OOH / 2 x.H20 2t5) / COOW2 SHCi.HgO tampeira- tuira top- inienda ° C 159.1 223.3 144.6 134.5 126 182.7 140.0 190.8 123 224 174.2 In an analogous manner it produces sii and also the compounds of formula I2, in which I /, s, R1 and A1 have the meaning given in Table 5. In this table, the symbol x means that the product was produced in the form of fumairain (2: 3), and the symbol xx denotes fumatran (1: 2), V -25 145 710 Taibela 5 2 * Compound number 1 206 207 208 209 2110 211 212 i2I3 214 215 216 217 218 219 220 221 222 223 224 225 226 L '2 formula 9 formula 9 formula 10 pattern 10 pattern 23 pattern £ pattern 23 pattern 23 pattern 18 pattern 9 pattern 24 pattern 23 pattern 18 pattern 24 - pattern 16 pattern 16 pattern 17 pattern 17 pattern 10 pattern 14 pattern 25 s 3 3 3 2 2 1 3 1 1 2 3 2 1 2 2 2 2 CSI 2 2 2 2 R1 4 CeHs- 4 - ^ - C6H4CH2- 2-fimainylmethyl- 4-F-C6H4CH2- 4-F-C6H4CH2- 4- / € Hy-C6H4CH2- 2-thiemylmethyl- 4 - / CH3 / -C6H4CH2- 4-F-CftH4CH2- 2-thiienylmethyl- 2-furanylmethyl- 2-pdridinylmethyl 2-furairphylmethyl- 4-F-C6H4CH2- 4-F-C6H4CH2- 2-furanylethyl- 2-furanylomeityl -C6H4CH2- 4-F-C6H4CH2- 4-F-C6H4CH2- 2-furanyl- A * 5 CH CH CH CH CH CH N CH CH N CH N CH CH CH CH CH CH NN CH Product form 1 6 problem XX principle rule ACOOH / 2 2 / COOH / 2 «2H2O / COOH ^ x-0.5 H2O2 / COOWa 1.5, / COOH ^ base 2.5i / COOH / 2 2.5 / COOH / 2 2 ^ COOH / 2 bases 2 (COOHiVH2O x Xbase 2.5l) COOH / tH2O 3) yCOOH / 2H2O "temperature ° C 7 160 146.1 210.3 177.2 198-200, 165.7 184.7 202.0 195.3 1.73.9 155.8 157 115.5 139.1 173.2 162 192.9 212.5 192.7 125.1 125.9 Compounds of formula I2 are prepared in a similar manner, where I /, s, R1 and A1 have the meanings given in Table 6. In this table, the symbols x and xx have the same meaning as in Table 5, and xxx means (1: 1) fumarate. Table 6 Product Compound number 227 228 229 230 23.1 232 233 234 235 2 »6 237 238 239 240 241 242 L '4-CHaO-C6H4- 4-F-C6H4-CO- 4-CH90-C6H4- C5H5-CH = CH- 4-CH3CK! 6H4- 4-CH $ 0-C6H4- / 4-F-C6H4 / ^ CH- 4-CH30-C6H4- ^ -F-CeH ^ -jCH- 4-CHaO-C6H4- C2H5-0-CO-NH- 4-CHsO- C6H4- 4-CH90-C6H4- ^ -F ^ CeH ^ / IzCH- Al-F-C6H4 / 2CH- 4-CHsO-C6H4- s 2 3 2 2 2 2 3 2 3 2 2 2 2 3 3 2 R1 4 -F-C6H4CH2- 4-F-CeH4CH2- 2-furanylmethyl 2-furainylmethyl C «H5 2-fcienylmethyl C &lt; H.5 2-pyridinylmethyl 4-F-C6H4CH2- 4-F-C6H4CH2- 2-thianyl omethyl 2-thienykmethyl 4- ^ CH ^ 6H4CH2- 2-thienylmethxl 4-CH3CgH4CH2- CHS Ai form melting point ° C CH N CH CH CH CH CH N CH NNN CH N CH CH XX XXX XX X xxx 2, COOH / 2 xx 2 / COOH / 2 2; cooh / 2 base xxx xxx l; € OOH / 2 2.5, / COOH / <2 2.COOH / 2 190 153.2 209.5 167.3 195.4 205.6 ^ 207.1 163.5-165.1 170 129.5 155.4 198.7 '214 192.2 116.8 164.9 Compounds of formula I8 are also prepared in an analogous manner where L', s, R1 a and A1 have the meanings given in Table 7, Compound number 1 246 247 248 249 250 251 252 253 254 256 257 258 259 260 261 262 263 1265 266 27 1/2 / CH3 / 2CH- ^ -F-CeH ^ - CH- C2H ^ CCV = O ^ NH- formula 9 C (jH5CH = CH- {4-OH3CM20H4- / CHj ^ CHhNH-C / ^ O / c2HgCcv = oyL 4-CHjO-C6H4 formula 18 formula 215 formula 13 4 -CH ^ O-CftH4- formula 18 formula 25 formula 25 formula 113 4-CH ^ O ^ C6H4- ¦s 3 teero 3 2 C 3 1 2 1 1 2 2 2 2 2 2 2 2 2 2 2 145 710 Table 7 R1-3 4 4-thiazoLylmethyl- 4-thiazioli (k) ime (only- 4-thiazoMiLmethyl- 2-pyridinylmethyl- HHH 4-F-C6H4CH2- 4-F-C6H4CH2- 2 »-pyridinylmethyl- 2-triefnylamines' 1- 2-pyridine lmethyl- 2-thielnylolmethyl- 3-furanylethyl- 4-thiazoLylorttyl- 4-taazoHLoinethyl- 2-thienylmethyl- 4-thiazoT.iylmethyl- -5-meityl-2-furanylornet! 5 CH CH CH N CH CH CH N CH N CH N CH CH CH CH CH CH CH CH 28 Product form 6 2, / OOOH / 2 2, COOH / 2 2 / COOH / 2 2 / COOH / 2 • H 2 O base base base 2HCl • H 2 O base base base base 2, COOH / 2 2.5i / COOH / 2 base base 2.5 / COOH / t • H 2 O 2 / COOH / -2- base 2 / COOH / 2 melting point 7 187-189 193—195 180.7 159 199.7 - 201.6 147.1 111.3 151.0 126.4 173.3 216.5 161.8 179.9 187.0 1P4 / 7 138.9 179.2 The compounds of formula 1 ^ are also prepared in a similar way, in which I /, s, R and the group - Ai - = Aj - A3 = A4 - are significant in Table 8. In this table, the symbol xx denotes salt with furnaric acid ( 2: 3) and xxx is fumarain (1: 1). Compound number 269 270 271 272 273 274 275 276 L '4-CHaO-C6H4 formula 18 4-CH30-C6H4 formula 18 4-CH30-C8H4 - formula 60 4-CH30-CeH4- 4-CH * 0-C6H4- 'S 2 2 2 2 2 2 2 2 RHHHHHHHH Table 8 - A1 = A »- A3 = A4 - -CH = CH-G / CH3 / = CH- CH = N-CH = CH- -CH = CH-OKCH ^ = CH- -CH = CH-CHi = N- -CH = CiOCHy-CH = CH- CH = CH-N = CH- -CH = CH -CJOW = CH- -CH = G / OH / -CH = CH- Frodukt ip form xx WCOOHJb 2HC1-1.5H20 21 (COOH (2 '0.5H2, O2 (COOH)) 2 ZftCOOWs • H2O xxx base melting point ° C 192.1 155.3 171.0 169.2 163.5 177.6 215 210 , 2 The compounds of formula I are prepared in an analogous manner, in which R, R1 and © rupa A1 = = A * —r A «= A * - have the meaning given in Table 9 ^ Compound No. 300 is obtained in the form of an isomer dis. Compound number 1 R 2 R1 3 Table 9 A * = A * - As = A4 - 4 Melting point ° C (5,283,284 HH 4-F-C6ACH2- CeH5- -CH = CH-CH = CH - -CH = CH-CH = CH- 146.5 141.8145 710 29 30 1 285 287 288 289 290 291 292 293 2) 94 295 296 297 298 299 300 301 2 HHHHHHHHHHHHHH CHj H 3 2-furanylmethyl- 2-thienylametyl - 3-pyridinylmethyl- 4-F-C6H4CH2- 2-furanylornethyl- 2-pyridinylmethyl- 4-CH30-C6H4CH2- H 4-CH3 ~ CflH4CH2- CeH4CH2- C6H ^ CH2- 4-CH30-C6H4CH2- 4- CH30-C6H4CH2 F-C6H4CH2- 4-F-C6H4CH2- 4-F-C6H4CH2- 4 -CH = CH-CH = CH- -CH = CH-CH = CH- -CH = CH-CH = CH- -CH = CH-CH = CH- -N = CH-CH = € H- -N = CH-CH = CH- -N = CH-CH = ICH- -CH = CH-CH = CH- -CH = CH-CH = CH- - CH = CH-CH = CH- -N = CH-CH = CH- -CH = CH-CH = CH- -N = CH * C H = CH- -OH = CH-CH = N-CH = CH-CH = CH- -OH = N-CH = CH- c.d. table 9 5 152.9 - - 91.7—93.2 98.2 124.7 137.3 1219.1 205.0 161.0 140.4 174.9 96.0 -1 127.9 132.4 The compounds with the formula I7 are also produced in a similar way, in which I /, R1-a IL A1 have the meaning given in table 10. In this table, the symbol x indicates that the compound was obtained in the form of a salt with fomiric acid (1: 3 ), and xx is the salt with fumaric acid (2: 3). Table 10 Niumer of the compound 334 335 336 337 338 339 340 341 342 343 344 345 L '2-ipdrimitidinyl-2-thiazoiiil-2-p-trimidinyl-2-pyrimid-Yinyl-2 -pdrymiidinyl- 2-pyrimidinyl- 2-pdrymiidyinyl- 2-pyrimidinyl- 2-pyrimidinyl- 2-pyrimidinyl- 2-pyrimidinyl- 2-pythyrinidinyl- nl ~ a 2-furanyl- 2-furiainyl- 2-thienyl- 3- pyridinyl- 4-thiazoliyl- 2-furanyl- 2-pyridinyl- 4-CH ^ OCeH4- 2-thiemyl- 4-CH ^ C6H4- C © H5- C © H5- A1 CH CH CH CH CH NN CH N CH CH N Product iposftac zaisalda X XX 4 ^ COOH / 2 4 / COOH / and 3 / COOH / 2 3.5C: OOH / 2 XX xx • H 2 O 2.5 ^ 0011/2 XX 3 / COOH / 2 mp. ° C 102, 5 159.3 184.1—188.4 176.5—130.9 192.7- ^ 194.6 107.9 151.2 182.8 1 52.3 160 194.5 172.9 The compounds of formula I8, in which L ', R1 and A1 have the meaning given in table 11, also prepared in a similar way. with flumaric acid (1: 3), and xx is respectively a salt with fumaric acid (2: 3). Table 11 Compound number L 'R1 A1 Product form melting point ° C 6 353 354 1357 ®53 2-thiaizolyl- 2-thiazolyl- 2-thiazolyl- 2-pyrimidinyl- 4 ^ F-C6H4CH2 C6H5- 4-F-C6H4CH2 H CH CH N CH base 2.5 / COOH / 2nd base U2Q 115.0 59.9 150.5 1 * 9.8145 710 31 32 ad. table 11 1 350 360 361 362 363 364 365 366 367 368 369 370 371 372 2-thiazolyl-5-ch] oaXH2-pd.ridine1- 2-thiazoM 2-thiaisoliI 2-thiaisoliyl 2-thiazolLl 2-tdazolyl 2-NO2 -C6H4- 2H-benzothiazoliiil- 2-pyrazinyl- 9-methyl-9H-purinyl-6 9H-purinyl-6 8-CH, 9-CH3-9Hipurinyl-6 * 8.9- / CH3 / 12-9H-ipurinyl-6 3 H 4-F-C6H4CH2- 2-thienylmethyl CflHgCH2- C © H5CH2- 4-CH3-C6H4CH2 4-CH30-C6H4CH2 4-F-C6H4CH2- 4-F-C6H4CH2- 4-F-C6H4CH2- 4-F-C6H4CH2- C6H4CH2 4-F-CeH4CH2- 4-F-C6H4CH2- 4-F-C6H4CH2- 4 CH CH NN OH CH N CH CH 'CH CH CH CH CH 5 sat base 3 ^ COOHA 3.5 / COOH / 2 VCOOH / 2 3 / COOH / g • H 2 O base 3i.5 / COOH / 2 '0.5H2O 2 / COOH /) 2 4HCl ¦ H 2 O base 2.5- / COOH / 2 base 6 180.7 - 129.1 129.1 142 , 3 138.0 144.5 120.9 167.5 173.1 2 (10.0 186.5 179.7 134.3 The useful properties of the antihistiaminic properties of the compounds of formula I have been demonstrated in the following tests. Protection of rats against lethal action of the agent 48/80 /. The agent known under the symbol 48/80 / is a mixture of oligomers obtained by 4-methoxy condensation. -N-methyloberizeinoethylarcinine with formaldehyde and, as reported in Int. Arreh, Allergy, 13, 336 (1958), is a potent hdistaimine trigger. Securing the effect of this agent-induced fatal circulatory failure is considered a simple method of quantifying the anti-histological activity of test compounds. Male Wiistar rats from one nest, weighing 240-260 g each, were used in the trials. ¬nosc 65 ± 5f% *. Rats were administered the test compounds subcutaneously or orally, alone or with a capillary (NJaCl solution, 0.9%), and after 1 hour, 48/80 intravenously injected agent 48/80 freshly dissolved in water , in doses of 0.5 mg / kg, i.e. 0.2 nu / l 00 g of the weight cdala. In comparative trials conducted without the test compounds of Formula 1, 260 rats were administered a typical dose of 48/80 and only 2.3% of animals were left alive. Survival longer than 4 hours is therefore considered an appropriate criterion for the protective effect of the compound. The ED5 <values of the tested compounds are given in the second column of Table 12, these are the values expressed in mg of the compound with the given number o 1 kg of animal body at which 50% of the tested compounds The animals are protected against the lethal action of the agent 48/80. The compounds of formula I and the pharmacologically acceptable acid addition salts are also potent serotond antagonists, as demonstrated by the tests described below. 25 35 40 45 50 A. Drug lesions 48/80 Agent 48/80 has a strong ability to release from endogenous reserves of vascular-affecting amines such as, for example, histamine and serotonin. Rats injected with this drug exhibit persistent lesions in circulation of blood in various vascular systems and cyanosis of the ears and limbs occurs already 5 minutes after the injection of this agent, and Within 30 minutes the animals are killed by the shock. This shock and death can be avoided if the rats are administered the known HI antagonistic order. However, this treatment did not inhibit the stimulating effect of the 48/80 on the glands of gastric juice secretion, and despite the administration of this HI antagonist preparation, although protected against shock, it manifested an intense activity of these glands, and the postmortem section shows an abnormally large number of rough stomachs. bright red streaks across the entire mucosa, corresponding to disintegrated glands. Numerous known substances that are serotonin antagonists, such as medicergtfd, cyproheptadine, synanserin, smianserin, pipamperon, spiperone, pizotifene and metergolin, completely prevent cyanosis of the ears and limbs, as well as lesions in the gastric glandular zone. and his abnormal gasps. B. Test method. Trials were conducted with male Wister rats walking up from one nest and weighing 220-55,250 g. Rats were starved overnight, given water ad libitum. Test compounds were administered (orally as a solution or an aqueous suspension. Test compounds were also administered to rats from the control and blank tests. After 60 hours, all rats were subcutaneously dosed with 5- {4-Aiviphenylmethyl) -1-pi. | Perazinylmethyl] -1H-methyl-1H-benzanidazolomethanol-2 at a dose of 2.5 mg / kg and 2 hours after the test was administered, the compound was administered to all rats, but B, except for the "blank" animals, intravenously33 145 the agent 48 ^ 80 in a dose of 1 mg / kg, in the form of a freshly prepared aqueous solution with a concentration of 0.25 mgtol. After 4 hours from the start of the sixdka 4 & / B0, the rat's heads were cut off, the stomachs were removed and their tears and contents were examined ( blood, liquid, food), and then the stomachs were carefully washed out and the condition of their interior was determined. the largest changes, in the form of reddish h, rough spots on more than half of the glandular area. In the third column of Table 12, the doses in mg of these compounds per 1 kg of rat weight are given for some compounds of formula 1, where at least 50% of rats have the stomach was not dizzy; no lesions were visible in the glandular area. These are the value} ND50. The dashes in the box 3 indicate that the given compound was not conducted in the test. Table 12 25 Dose ED50 Dose ED59 in m ^ g Paedw- Num € fl: in mg ^ kg inhibitory Burning sickness - lethal to tormentors 30 casting measure 48/80 *** & * Caused by measure 4B / 80 8 28 25 81 82 83 86 89 90 93 94 100 101 102 103 107 110 112 113) 115 116 117 118 123 124 126 127 128 129 130 131 0.04 0.08 0.16 0.08 0.005 0.01 0.01 0.04 0.01 0.04 0.08 0.16 0.02 0.02 0.005 0.04 0.02 0, 08 0.08 0.16 0.16 0.01 0.04 0.01 0.04 0.04 0.08 0.16 0.16 0.16 0.02 35 40 0.63 0.31 0, 63 0.31 0.31 0.16 0.08 50 _ ^ 55 0.65 0.31 0.63 60 0.63 0.63 0.10 65 145 710 36 cd table 12 continued table 12 388 0.16 - 392 0.02 0.63 - 394 0.02 - C, 63 416 0.04 0.04 - 417 0.04 - 0.16 418 0.02 0.04 0.04 10 422 0.04 0.04 0.63 427 0.16 - - 431 0.04 0.005 - 432 0.04 0.31 - 433 0.01 0.16 0.63 15 434 0.0025 - 0.31 436 0.01 0.63 - 438 0.0-8 0.16 0.31 439 0.16 0.31 0.63 440 0.02 -. - 20 441 0.08 0.16 - 443 0.02 0.16 - 444 0y16 - - 445 0.16 - - 448 0.08 0.16 0.16 25 452 0.16 - 0.02 453 0, 04 0.02 0.08 455 0.04 0.63 0.31 456 0.01 0.63 0 "16 459 0.02i - Q, 08 30 4 ^ 0 0.08 0.63 - 466 0.02 - - 467 0.04 0.08 - 468 0.02 0.63 0.16 470 0.04 - - 35 472 0.04 - - 473 0.02 - 0.63 477 0.02 0.63 0, 04 478 0.02 0.04 0.08 479 0.04 —i - 40 489 0.08 0.63 0.63 490 0.31 -. - 403 0.08 0.04 0.63 495 0.04 0.16 - 498 0.08 0.16 - 45 499 0.04 0.01 - 500 0.01 - ^ - 501 0.04 - 0, 16 502 0.08 0.16 - 504 0.08 0.63 - 50 507 0.16 - - 508 0.08 0.16 0.63 510 0.02 0.16 0.16 511 0.16 - - 512 0.08 - 0.02 55 514 0.02 0.63 0.63 515 0.16 - - 516 0.16 - - <523 0.04 0.31 0.31 524 0.16 - 0.63 60 0.16 0.63 The compounds of formula I and their acid addition salts 0.16 are themselves due to their antihypertensive properties 0.63 and their antihypertensive ability serojtooiinie 0 "08 65 very useful in the treatment of allergic diseases, 145 710 37 3 * such as, for example, allergic rhinitis, allergic conjunctivitis, chronic urticaria and allergic asthma. These compounds can be used in various formulations, depending on their purpose and mode of administration. In the preparation of these preparations, the compounds according to the invention are mixed as active substances in suitable ratios with pharmacologically acceptable carriers suitable for the intended method of administration of the preparations. These preparations can be administered orally, rectally, subcutaneously, or by parenteral injection. In the preparation of oral preparations, substances normally used for these purposes are used as carriers, for example, "water, glycols, oils and alcohols in the case of liquid preparations, such as suspensions, syrups and solutions, or solid carriers e.g. In parenteral preparations, the carrier is usually, at least for the most part, water, but other additives may also be used, for example, to increase the solubility of the active substance. a glucose solution or both. Injections may also take the form of suspensions, and in such cases an addition of a substance may be used in addition to a liquid carrier to facilitate the injection. the preparation of a suspension. Preparations for administration through the skin, the carrier may contain the addition of a permeation aid and / or a wetting agent, as well as small amounts of other substances, not harmful to the skin, but facilitating the preparation of the bed. These agents are administered in various ways, e.g. as poultices, topicals or as ointments. The acid addition salts of the compounds of formula I are more easily soluble in water than the corresponding free bases and are therefore better suited for the preparation of water-based preparations. These preparations are preferably prepared in the form of unit doses containing a specific amount of active substance adapted to the therapeutic effect which the dose is to produce. Examples of such preparations are tablets, coated tablets, capsules, pills, powder packets, wafers, injectable solutions and suspensions in containers. These preparations are used in such a way that the daily dose of the active substance is 0.1-100 mg, preferably 1-60 mg. Possible objection A method for the preparation of new piperidine bicyclic derivatives of the general formula I, in which the group -A1 = A2 - A8 = A4 - is a bivalent radical of the formula —CH = CH — CH = = CH—, —N = CH — CH = CH—, —CH = N — CH = CH—, —CH = -CH- ^ N = CH— or - - CH = CH - CH = N - in which the radicals 1 or 2 and the hydrogen atoms can be replaced by the same or different substituents, such as halogen atoms, lower alkyl radicals, lower alkoxy groups or hydroxyl groups, R 1 is a hydrogen atom, a lower alkyl radical, a cycloalkyl radical, an aryl radical, an aryl lower alkyl radical, or a diphenylmethyl radical, wherein R1 as the aryl radical is a phenyl radical, optionally having 1 or 2 substituents, such as halogen atoms, lower alkyl radicals, lower alkoxy groups or trifluoromethyl groups, or is a thienyl group or is a furyl group, optionally substituted with a lower alkyl radical, or is also a pyridinyl, pyrazinyl, thiazolyl or naphthyl radical, R2 is a hydrogen atom or a lower alkyl radical, and L represents a group of formula II, in which the symbols r and s are the same or different and each of them represents the number zero or an integer 1-6 and one or two hydrogen atoms in the bivalent radical "CsH2s" can be replaced independently from each other with hydroxyl groups, the lower groups, aUckoxy, phenyl or halophenyl radicals, and T represents a substituent of the symbol "Y" or a group of the formula Z — CV = Xi / 1 — Y'— where Y represents an oxygen atom, direct bonding or a group of of the formula = NR3 in which R3 is a hydrogen atom, a lower alkyl radical, a lower alkalicarbonyl group, a furylcarbonyl group, a group of the formula Ar2 - allyklLl lower or Ar2 - carbonyl in which the formulas Ar2 denotes a phenyl radical, optionally having up to three substituents which are the same or different, such as halogen atoms, hydroxyl groups, nitro groups, cyanides, trifluoromethyl groups, lower alkyl, alkoxy or alkylthio groups, mercapto groups, amino or carboxyl groups, lower mono groups or dialkylamino, lower alkyloxycarbonyl or alkalocarbonyl groups, Y 'represents an oxygen atom, the group = NH February direct bond, X represents an oxygen atom, a sulfur atom or a group of formula = NR4, where R4 is a hydrogen atom or a lower alkyl radical, and Z represents an oxygen atom, a direct bond kypho group of formula = NR5, wherein R5 is hydrogen or a lower alkyl radical, and L.1 in formula IIi is hydrogen or halogen, © rupe. cyano, isocyanate, lysothiocyanate, thienylcarbonyl, cycloalkyl, naphthyl or the above-described group Ar2, or the group Ar2-sulfanyl, where Ar2 is as defined above, where when r is zero, L1 can also be a lower alkenyl group, then a group Ar2-alkenyl, in which Ar2 is as defined above, or a lower alkyl group substituted with two lower alkyl phenyl groups, and L1 also represents a group with the symbol Het which represents a pyridinyl group, optionally having 1 or 2 identical or different substituents such as halogen atoms, amino groups, lower alkyl or alkoxy groups, pyridinyl oxide groups, optionally substituted nitro groups, pyrimidinyl groups, optionally having 1 or 2 identical or different substituents, 40 45 50 55 60 145 710 39 40 such as halogen atoms, almiino groups and lower alkyl or attkoxy groups, pyridazinyl grape, optionally substituted with lower an alkyl radical or halogen atom, a pinazinyl group, optionally substituted with a halogen atom, an aniline or lower alkyl radical, a thienic group, optionally substituted with a cMoro or lower alkyl radical, a furyl group, optionally substituted with a lower alkyl radical or a halogen atom , pyridonic group, optionally substituted with a lower alkyl radical, a tna isoMyl group, optionally substituted with a lower alkyl radical, a lower alkoxycarbonyl group or a group with the above symbol Ar *, a tefcrazolium group, possibly a lower alkyl group, with the lower alkyl group, Optionally having 1 or 2 identical or different substituents, such as lower alkyl radicals or nitro groups, a 4,5-dihydro-5-keto-1H-tetraiso-liyl group, optionally substituted with a lower alkyl radical, the group chonoliinyl, optionally substituted hydroxyl or lower alkyl, phthase ynyl, optionally substituted with halogen, morpholinyl, 2,3-hydro-3-keto-4H-beriZOxazinyl, 2 -3-o-yo-1-, 4-benzodioxinyl, dioxanyl gruipe, 2-keto-2H-1-benzopyranyl group, 4-keto-4H ^ 1-taenzopyranyl group, 2,4-dihdw? - ^ 4-biceto-3i /) lH ^ pyrim Iowa group, group 4 -kelto-i2 ^ 1H / -piiryrnMynyik) wa, 2-keto-3-oxazoMdynya group or indolite group, or also Het is a group of formula 3a, 3b, 3c, 8d, 3e * 3f, 3g, 3h or 3i, X2 in the formulas 3a, 3h, 3c and 3 of the formula 3a the X * substituents may be the same or different, the substituents R11, R * 1, R14, R »" ': R »and RM correspond to the formulas 3a, 3c, 3g and 3h represent hydrogen atoms or lower alkyl radicals, where in formula 3a the substituents R11 and R12 may be the same or different, subfetavtraiM Rw, R18, R17, Rw, R19, R * °, R "and R2 * respectively in the formulas 3b, 3c , 3d, 3e, 3f and 3g are hydrogen atoms, lower alkyl radicals, hydroxyl groups, mercapto groups, lower alkoxy or alkyl groups. thio or halogen atoms ^ with R17 and R19 in formula 3d and R19 and RM in formula 3e may be the same or different, G1 in switch 3a represents the group —CH = CH — CH = = CH—, —S — CH = CH— or - ^ N = CH- ^ NH, G2 in formula 3d means the group —CH = CH — CH = CH—, - ^ - / CH ^ -, -S / CH2A—, - ^ CH2 / 4— or - ^ S— —CH ^ CH—, G * in the formula 3e means the group -hCH = CH — CH = CH—, - CH2 ^ NH - ^ / CH2 / 2—, —S— —CH ^ CH ^ - or - N = CH- ^ CH = CH, G * in the formula 3f represents the group —CH2 — NH — v / CH2 / 2, —N = = CH — CH = CH — ^ CH = N — CH = CH—, - CH = = CH-N = CH-, -CH = CH-CH = CH-, -CH = CH-CH = = N -N = CH-N = CH- or -CH = N-CH = N, G * e 10 15 90 35 40 45 50 55 formula 3g means the group -N = CH-CH = CH-, -C11 = = N — CH = CH—, —CH = CH- ^ N = CH- ^, —CH = CH - —CH = N—, - ^ CH = CH ^ CH = CH—, - ^ N = CH — N = = CH— or ^ CH = N — CH = N— and G ”in formula 3h means the group —CH = CH — OH = CH — i —-N = = CH — CH = CH—, - ^ CH = N- ^ CH = CH, —CH = CH— -hN = CH—, —CH = CH — CH = N— , —N = CH — N = = CH— or —CH = N — CH = N, one or two hydrogen atoms in these G1-G6 groups or in the benzene ring in the groups of formulas 3b, 3c and 3i can be replaced they are lower alkyl, alkylthio 'or alkoxy groups or halogen atoms, and when bonded to nitrogen atoms, they can be replaced by lower alkyl radicals, while the group of formula 3a, 3d, 3e, 3f, or 3g is associated with the group of the above of the formula CsH2s on a carbon atom that could have the substituent R11, R12, R17, R18, R ", R", R ", R2 * Vb R *", respectively, then the substituents of these symbols are absent, where: L1 represents a hydrogen atom and T represents a group of the formula (Z — CV = X) and —Y1, in which Y 'is as defined above, but except for a direct bond, Z represents a oxygen atom and L X represents a oxygen or sulfur, then r in formula II represents an integer 1-6 or when L1 represents a halogen atom, an isocyanate group, an isothiocyaninine group or the above-described Het group associated with the above-described group of the formula CrH2 on the nitrogen atom and when r is zero, then T is a direct bond or a group of the above-described formula -C / :: = X / -Y 'and when T represents the symbol Y Or the group of formula -Z-C / l = = X / -Y', and Y or Y 'have the meaning given above, but with the exception of direct linkage, then s in formula 2 (represents the integer X-6 or the pharmacologically acceptable acid addition salts of compounds of formula I or stereoisomers of these compounds, characterized in that the piperidine derivative of formula IV in which L and R2 are as defined above. = NH and W is chlorine or bromine, or an alkoxy or hydroxy group is reacted in an inert solvent such as an alcohol, especially methanol or ethanol, or an acid such as acetic acid, with a diamine of formula 5 in which The meaning of R1 and the group of formula "A1 = A" -nA * = A * have the meaning given above, whereby, when using a compound of formula% in which W is a hydroxyl group, the reactions are carried out in the presence of a dehydrating agent. , such as polyLphosphoric acid or phosphorus oxychloride, and optionally the presence of a base such as N, N -deviethylbenzirloamdnai, and then the resulting compound of formula I is optionally converted to its acid addition salt. ^ w r4 Formula 11 R Formula V CH2-R1_Q IMCH2) sN ^ CH2 ^ yAS n — l! ^ 'Formula V LLNH-CHZ-CH2-N H f 1 JM * a1 CH Formula 18 2 and 2 N- G1 LLCr ^ rT-CsH2s Formula 2 R11 lWX2 N-R12 Formula 3a R * R15 Mr16 X2 Formula 3c Formula 3e caR * Formula 3b 0 Formula 3d Formula 3f145 710 CHfR1-0 i, * i Ll-lCH2) sN ^ CH2y ^ A ^ j Formula 1 CH2- <-ich2) s-OCH2YnY ^ R Formula 1 'R f? 1 I. a1 NC-CH, -0 N — kM Formula VH CH2-R 1-L ll-NH-CHfCHfOc ^ - ^ n Formula \ l R 22 € ¥. '. .D23 Nv ^ RN Formula 3g 0 W Formula 3i RM Formula 3h Vq L-lfOtC-W Formula 4 R1 hi ^ yaW HgN Formula 5 L- N ^ 5br (r3) n OKicrr Formula 6145 710 / R2 L-N _} - CH2CN Formula 7 * ^ S NvJJ Formula 9 0 Formula 11 Formula 13 o Formula 1S Formula 10 o Formula 12 0 Formula V * ^ \. Nk CH3 O Formula 18 N LCH3 Formula 20 LN3 VNvN ^ T Ti J CHrN N- 0 Formula 17 CH2 -CH3 N — N Formula 19 Formula 21 Formula 22 co Formula 23 CH * ^ S ^ N ^ XH3 / - \ ^ NyCH3 Formula 2U O Formula 25 PL EN

Claims (1)

1. Patent claim A method for the preparation of new double-ring piperidine derivatives of the general formula 1, in which the group —A1 = A2 - A8 = A4 - is a bivalent radical of the formula —CH = CH — CH = = CH—, —N = CH— CH = CH—, —CH = N — CH = CH—, —CH = -CH- ^ N = CH— or - ^ CH = CH ^ CH = N— in which radicals 1 or 2 and hydrogen atoms can be replaced by the same or with various substituents such as halogen atoms, lower alkyl radicals, lower alkoxy groups or hydroxyl groups. diphenylmethyl, where R 1 as the aryl radical is a phenyl radical, optionally having 1 or 2 substituents, such as halogen atoms, lower alkyl radicals, lower alkoxy groups or trifluoromethyl groups, or is a thienyl group, evovalin substituted with halogen or a lower alkyl radical, or is a furyl s, optionally substituted with a lower alkyl radical, or is also a pyridinyl, pyrazinyl, thiazolyl group or a naphthyl radical, R 2 is a hydrogen atom or a lower alkyl radical, and L is a group of formula II, in which the symbols are the same or different and each of them represents a number zero or an integer 1-6, and one or two hydrogen atoms in the divalent radical —CsH2s— can be replaced, independently of each other, by hydroxyl groups, the lower groups of a, ukoxy, phenyl or halogenated phenyl radicals, T represents a substituent of the symbol —Y— or a group of the formula Z — CV = Xi / 1 — Y'— wherein Y is an oxygen atom, a direct bond, or a group of the formula = NR3, in which R3 is a hydrogen atom, lower alkyl radical, lower an alkalocarbonyl group, a furylcarbonyl group, a group of the formula Ar2-lower alliclIl or Ar2-carbonyl, in which formulas Ar2 is a phenyl radical, optionally having up to three substituents that are identical or different, such as halogen groups, hydroxyl groups, nitro groups, cyanides, trifluoromethyl groups, lower alkyl, alkoxy or alkylthio groups, mercapto groups, amine or carboxyl groups, lower mono- or dialkylamino groups, lower alkyloxycarbonyl or alkalocarbonyl groups, are oxygen, Y ' group = NH, direct bond, X is oxygen, sulfur or a group of formula = NR4, where R4 is hydrogen or a lower alkyl radical and Z is oxygen, direct bond to kypho group of formula = NR5, wherein R5 is hydrogen or a lower alkyl radical and L.1 in formula IIi is hydrogen or halogen, © rupe. cyano, isocyanate, lysothiocyanate, thienylcarbonyl, cycloalkyl, naphthyl or the above-described group Ar2, or the group Ar2-sulfanyl, where Ar2 is as defined above, where when r is zero, L1 can also be a lower alkenyl group, then a group Ar2-alkenyl, in which Ar2 is as defined above, or a lower alkyl group substituted with two lower alkyl phenyl groups, and L1 also represents a group with the symbol Het which represents a pyridinyl group, optionally having 1 or 2 identical or different substituents such as halogen atoms, amino groups, lower alkyl or alkoxy groups, pyridinyl oxide groups, optionally substituted nitro groups, pyrimidinyl groups, optionally having 1 or 2 identical or different substituents, 40 45 50 55 60 145 710 39 40 such as halogen atoms, almiino groups and lower alkyl or attkoxy groups, pyridazinyl grape, optionally substituted with lower an alkyl radical or halogen atom, a pinazinyl group, optionally substituted with a halogen atom, an aniline or lower alkyl radical, a thienic group, optionally substituted with a cMoro or lower alkyl radical, a furyl group, optionally substituted with a lower alkyl radical or a halogen atom , pyridonic group, optionally substituted with a lower alkyl radical, a tna isoMyl group, optionally substituted with a lower alkyl radical, a lower alkoxycarbonyl group or a group with the above symbol Ar *, a tefcrazolium group, possibly a lower alkyl group, with the lower alkyl group, Optionally having 1 or 2 identical or different substituents, such as lower alkyl radicals or nitro groups, a 4,5-dihydro-5-keto-1H-tetraiso-liyl group, optionally substituted with a lower alkyl radical, the group chonoliinyl, optionally substituted hydroxyl or lower alkyl, phthase ynyl, optionally substituted with halogen, morpholinyl, 2,3-hydro-3-keto-4H-beriZOxazinyl, 2 -3-o-yo-1-, 4-benzodioxinyl, dioxanyl gruipe, 2-keto-2H-1-benzopyranyl group, 4-keto-4H ^ 1-taenzopyranyl group, 2,4-dihdw? - ^ 4-biceto-3i /) lH ^ pyrim Iowa group, group 4 -kelto-i2 ^ 1H / -piiryrnMynyik) wa, 2-keto-3-oxazoMdynya group or indolite group, or also Het is a group of formula 3a, 3b, 3c, 8d, 3e * 3f, 3g, 3h or 3i, X2 in the formulas 3a, 3h, 3c and 3 of the formula 3a the X * substituents may be the same or different, the substituents R11, R * 1, R14, R »" ': R »and RM correspond to the formulas 3a, 3c, 3g and 3h represent hydrogen atoms or lower alkyl radicals, where in formula 3a the substituents R11 and R12 may be the same or different, subfetavtraiM Rw, R18, R17, Rw, R19, R * °, R "and R2 * respectively in the formulas 3b, 3c , 3d, 3e, 3f and 3g are hydrogen atoms, lower alkyl radicals, hydroxyl groups, mercapto groups, lower alkoxy or alkyl groups. thio or halogen atoms ^ with R17 and R19 in formula 3d and R19 and RM in formula 3e may be the same or different, G1 in switch 3a represents the group —CH = CH — CH = = CH—, —S — CH = CH— or - ^ N = CH- ^ NH, G2 in formula 3d means the group —CH = CH — CH = CH—, - ^ - / CH ^ -, -S / CH2A—, - ^ CH2 / 4— or - ^ S— —CH ^ CH—, G * in the formula 3e means the group -hCH = CH — CH = CH—, - CH2 ^ NH - ^ / CH2 / 2—, —S— —CH ^ CH ^ - or - N = CH- ^ CH = CH, G * in the formula 3f represents the group —CH2 — NH — v / CH2 / 2, —N = = CH — CH = CH — ^ CH = N — CH = CH—, - CH = = CH-N = CH-, -CH = CH-CH = CH-, -CH = CH-CH = = N -N = CH-N = CH- or -CH = N-CH = N, G * e 10 15 90 35 40 45 50 55 formula 3g means the group -N = CH-CH = CH-, -C11 = = N — CH = CH—, —CH = CH- ^ N = CH- ^, —CH = CH - —CH = N—, - ^ CH = CH ^ CH = CH—, - ^ N = CH — N = = CH— or ^ CH = N — CH = N— and G ”in formula 3h means the group —CH = CH — OH = CH — i —-N = = CH — CH = CH—, - ^ CH = N- ^ CH = CH, —CH = CH— -hN = CH—, —CH = CH — CH = N— , —N = CH — N = = CH— or —CH = N — CH = N, one or two hydrogen atoms in these G1-G6 groups or in the benzene ring in the groups of formulas 3b, 3c and 3i can be replaced they are lower alkyl, alkylthio 'or alkoxy groups or halogen atoms, and when bonded to nitrogen atoms, they can be replaced by lower alkyl radicals, while the group of formula 3a, 3d, 3e, 3f, or 3g is associated with the group of the above of the formula CsH2s on a carbon atom that could have the substituent R11, R12, R17, R18, R ", R", R ", R2 * Vb R *", respectively, then the substituents of these symbols are absent, where: L1 represents a hydrogen atom and T represents a group of the formula (Z — CV = X) and —Y1, in which Y 'is as defined above, but except for a direct bond, Z represents a oxygen atom and L X represents a oxygen or sulfur, then r in formula II represents an integer 1-6 or when L1 represents a halogen atom, an isocyanate group, an isothiocyaninine group or the above-described Het group associated with the above-described group of the formula CrH2 on the nitrogen atom and when r is zero, then T is a direct bond or a group of the above-described formula -C / :: = X / -Y 'and when T represents the symbol Y Or the group of formula -Z-C / l = = X / -Y', and Y or Y 'have the meaning given above, but with the exception of direct linkage, then s in formula 2 (represents the integer X-6 or the pharmacologically acceptable acid addition salts of compounds of formula I or stereoisomers of these compounds, characterized in that the piperidine derivative of formula IV in which L and R2 are as defined above. = NH and W is chlorine or bromine, or an alkoxy or hydroxy group is reacted in an inert solvent such as an alcohol, especially methanol or ethanol, or an acid such as acetic acid, with a diamine of formula 5 in which The meaning of R1 and the group of formula "A1 = A" -nA * = A * have the meaning given above, whereby, when using a compound of formula% in which W is a hydroxyl group, the reactions are carried out in the presence of a dehydrating agent. , such as polyLphosphoric acid or phosphorus oxychloride, and optionally the presence of a base such as N, N -deviethylbenzirloamdnai, and then the resulting compound of formula I is optionally converted to its acid addition salt. ^ w r4 Formula 11 R Formula V CH2-R1_Q IMCH2) sN ^ CH2 ^ yAS n — l! ^ 'Formula V LLNH-CHZ-CH2-N H f 1 JM * a1 CH Formula 18 2 and 2 N- G1 LLCr ^ rT-CsH2s Formula 2 R11 lWX2 N-R12 Formula 3a R * R15 Mr16 X2 Formula 3c Formula 3e caR * Formula 3b 0 Formula 3d Formula 3f145 710 CHfR1-0 i, * i Ll-lCH2) sN ^ CH2y ^ A ^ j Formula 1 CH2- <-ich2) s-OCH2YnY ^ R Formula 1 'R f? 1 I. a1 NC-CH, -0 N — kM Formula VH CH2-R 1-L ll-NH-CHfCHfOc ^ - ^ n Formula \ l R 22 € ¥. '. .D23 Nv ^ RN Formula 3g 0 W Formula 3i RM Formula 3h Vq L-lfOtC-W Formula 4 R1 hi ^ yaW HgN Formula 5 L- N ^ 5br (r3) n OKicrr Formula 6145 710 / R2 L-N _} - CH2CN Formula 7 * ^ S NvJJ Formula 9 0 Formula 11 Formula 13 o Formula 1S Formula 10 o Formula 12 0 Formula V * ^ \. Nk CH3 O Formula 18 N LCH3 Formula 20 LN3 VNvN ^ T Ti J CHrN N- 0 Formula 17 CH2 -CH3 N — N Formula 19 Formula 21 Formula 22 co Formula 23 CH * ^ S ^ N ^ XH3 / - \ ^ NyCH3 Formula 2U O Formula 25 PL EN