Substituted cyclohexylmethyl derivatives


FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cyclohexylmethyl derivatives, having serotonin, noradrenaline or opioid receptor inhibiting activity, optionally in form of cis- or trans-diastereomers or mixture thereof in form of bases or salts with physiologically compatible acids. In formula (1): R2 denotes H or OH; R1 and R2 together denote or =N-OH, R3 denotes a phenyl residue which is unsubstituted or monosubstituted with a halogen atom or a heteroaryl residue selected from a five-member sulphur-containing heteroaryl such as a thienyl residue or an unsubstituted phenyl residue bonded through a C1-C4alkyl group, R4 and R5 independently denote an unsubstituted C1-C3alkyl or R4 and R5 together denote (CH2)3-6, R8 denotes a linear saturated C1-C4 alkyl group bonded with an aryl, which is unsubstituted or monosubstituted with halogen atoms, R9 denotes a saturated C1-C8alkyl; values of radicals R1, m, n, R6, R7, R10-R13 are given in the claim. The invention also relates to methods of producing compounds of formula (I), a medicinal agent containing said compounds, use of compounds of formula (I) to prepare a medicinal agent for anaesthetic treatment during sharp, neuropathic or chronic pain and for treating depression, urinary incontinence, diarrhoea and alcoholism.

EFFECT: high efficiency of using the compounds.

32 cl, 501 ex, 21 tbl

 

The text descriptions are given in facsimile form.

1. Substituted derivatives of cyclohexylmethyl General formula I

in which
R1denotes unbranched, saturated, unsubstituted or one-deputizing C1-C8alkyl, and the substituents are selected from =O, CO2C1-C4-alkyl; phenyl residue, unsubstituted or mono - or dvuhkamernyi halogen, C1-C4-alkyl, OC1-C4-alkyl, phenyl residue, unsubstituted or mono - or dvuhkamernyi halogen, Halogens1-C4-alkyl; attached via C1-C4is an alkyl chain is unsubstituted or one - or dvuhkamernyi phenyl residue, with the substituents specified in the phenyl residue selected from halogen, OC1-C4-alkyl; the group (CH2)mCHN-OH group (CH2)nNR6R7group (CH2)nOR8where n denotes 0, 1, 2 or 3, a m denotes 0, 1; joined us through the seal or unsaturated C 1-C3-alkyl group, C(O)OR9or a group CONR10R11,
R2denotes H or OH;
R1and R2together denote,or =N-OH
R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6,
R6denotes H, a saturated, branched or unbranched, unsubstituted C1-C8-alkyl, phenyl residue, unsubstituted or substituted by a group OC1-C3-alkyl, phenyl, attached via C1-C4is an alkyl group with straight or branched chain, unsubstituted or substituted with halogen or OC1-C4is an alkyl group, or unsubstituted nitrogen-containing 5-membered heteroaryl condensed with a benzene ring such as indole;
R7denotes H, a saturated, branched or unbranched, unsubstituted C1-C8-alkyl, phenyl residue, one-deputizing groups selected from OC -C4-alkyl, halogen, attached via C1-C4is an alkyl chain of the phenyl residue, one-deputizing OC1-C4-alkyl, or unsubstituted nitrogen-containing C5heteroaryl residue, condensed with phenyl, such as indole; C(O)NR10R11C(S)NR10R11, SO2R12or C(O)R13,
R8denotes unbranched saturated C1-C4is an alkyl group associated with aryl, unsubstituted or monosubstituted by halogen atoms,
R9denotes a saturated C1-C8-alkyl,
R10and R11independently of one another denote H, C1-C8-alkyl, unsubstituted C6-cycloalkyl, C6-C10-aryl residue, unsubstituted or mono - or dvuhkamernyi substituents from the group comprising OC1-C4-alkyl, halogen-substituted C1-C4-alkyl, halogen, NO2or attached via C1-C4is an alkyl chain is unsubstituted aryl or 6-membered nitrogen-containing heteroaryl residue, for example pyridyl, and R10and R11are not simultaneously denote H,
R12denotes a phenyl residue, unsubstituted or one-deputizing substituents from the group comprising halogen, NO2C1-C4-alkyl or OC1-C4-alkyl;
R13denotes intense, razvetvlennye non-branched C 1-C8-alkyl, unsubstituted or one - or dvuhkamernyi substituents from the group comprising C1-C6-alkyl, O-benzyl, phenyl and O-phenyl, and O-phenyl substituted with halogen; C5-C10-cycloalkenyl residue, which is unsubstituted or odnosnie by phenyl, and phenyl substituted with halogen; C6-C10-aryl or 5-membered heteroaryl residue containing 1-3 heteroatoms in the ring selected from N, O, and S, which may be condensed with a benzene ring, and the specified C6-C10is aryl or heteroaryl residue contain 1-5 substituents from the group including halogen, CN, NO2, pyridyl, thienyl, (CH2)O-C1-C6alkyl, phenyl, unsubstituted or substituted by one or two Halogens, dihydrobenzofuran, C1-C4-alkyl straight or branched chain containing one or more substituents selected from the group comprising halogen or OC1-C6-alkyl, OC1-C6-alkyl, S-phenyl or O-phenyl, each of which is substituted by halogen or C1-C6-alkyl, S-C1-C6-alkyl, SO2phenyl, unsubstituted or substituted with one halogen, C3-C6-cycloalkyl attached through a bridging group C1-C4-alkyl, SO2C1-C6alkyl straight or branched chain, or denotes thienyl attached h the rez C 1-C4is an alkyl chain, phenyl containing one Deputy, and the Deputy is chosen from the group comprising halogen or OC1-C4-alkyl,
not necessarily in the form of CIS - or TRANS-diastereomers or mixtures thereof in the form of bases or of salts with physiologically compatible acids.

2. Substituted derivatives of cyclohexylmethyl according to claim 1, in which R1denotes unbranched, saturated C1-C8-alkyl, unsubstituted or substituted by one Deputy, and the Deputy is chosen from a group =O, CO2C1-C4-alkyl; phenyl residue, unsubstituted or mono - or dvuhkamernyi halogen, C1-C4-alkyl, OC1-C4-alkyl; attached via C1-C4is an alkyl chain is unsubstituted or one - or dvuhkamernyi phenyl residue, with the substituents specified in the phenyl residue selected from halogen, OC1-C4-alkyl, and R2denotes OH.

3. Substituted derivatives of cyclohexylmethyl according to claim 1, in which R1refers to a group (CH2)mCHN-OH, (CH2)nNR6R7or (CH2)nOR8where n denotes 0, 1, 2 or 3, a m denotes 0, 1, attached via a saturated or unsaturated C1-C3-alkyl group, C(O)OR9or a group CONR10R11and R2denotes H.

4. Substituted about spodnie of cyclohexylmethyl according to claim 1 or 2, in which R1denotes unbranched, saturated C1-C8-alkyl, which is substituted by one Deputy from the group including =O, CO2C1-C4-alkyl, or phenyl residue, which is not substituted or mono - or dunamase halogen, C1-C4-alkyl, OC1-C4-alkyl.

5. Substituted derivatives of cyclohexylmethyl according to claim 1 or 2, in which R1denotes 2,4-differenl, 4-fluoro-3-were, phenyl, 3-methoxybenzyl, 4-chlorophenyl, benzyl, 2-were, 4-tert-butylphenyl, 4-forfinal, phenethyl, 2,4-dichlorophenyl, 3-methoxyphenyl, 4-were, 4-methoxyphenyl, 3,5-differenl, butyl, ethyl, hexyl, pentyl, propyl, 3-forfinal, 3,5-dichlorophenyl, 4-tormentil, 4-chloro-3-triptoreline or 2.5-acid.

6. Substituted derivatives of cyclohexylmethyl one of claims 1 to 3, in which R3denotes a phenyl residue, which is not substituted or odnosnie substituents from the group comprising halogen atom, thienyl or attached via C1-C3is an alkyl chain of the phenyl residue.

7. Substituted derivatives of cyclohexylmethyl according to claim 6, in which R3denotes phenyl which is not substituted or odnosnie atom Cl or F, phenethyl or thienyl.

8. Substituted derivatives of cyclohexylmethyl one of claims 1 to 3, in which R4and R5denote C1-C3-alkyl.

Thomasenia derivatives cyclohexylmethyl according to claim 1 or 3, in which R6denotes H, a saturated branched or unbranched, unsubstituted C1-C8-alkyl, phenyl residue, unsubstituted or substituted by a group OC1-C3-alkyl, phenyl, attached via C1-C4is an alkyl group with straight or branched chain, substituted or unsubstituted substituents from the group comprising F, Cl, Br, and OC1-C4is an alkyl group.

10. Substituted derivatives of cyclohexylmethyl according to claim 1, in which R6means phenethyl, 3-phenylpropyl, benzyl, 4-phenylbutyl, in each case substituted by one or more substituents, which are selected from the group comprising F and OCH3, phenyl, unsubstituted or substituted with one group OCH3, unsubstituted indole.

11. Substituted derivatives of cyclohexylmethyl of claim 10, in which R6denotes H.

12. Substituted derivatives of cyclohexylmethyl according to claim 1 or 3 in which R7denotes C(O)R13.

13. Substituted derivatives of cyclohexylmethyl according to claim 1 or 3 in which R8means attached via C1-C4is an alkyl group, a phenyl residue, which is not substituted or monogamist substituents selected from F, Cl or Br.

14. Substituted derivatives of cyclohexylmethyl indicated in paragraph 13, in which R8denotes a benzyl, which is not substituted or monogamist atoms F.

15. Thames is installed derivatives cyclohexylmethyl according to claim 1 or 3, in which R9denotes unbranched C1-C8-alkyl.

16. Substituted derivatives of cyclohexylmethyl according to claim 1 or 3 in which R10and R11independently of one another represent H, phenyl, naphthyl or attached via C1-C4is an alkyl chain is unsubstituted phenyl residue.

17. Derivatives cyclohexylmethyl by 14 in which R10and R11independently of one another denote H, nattily, phenyl or benzyl residue, which is not substituted or odnosnie substituents from the group comprising CF3F, NO2and Br, provided that R10and R11simultaneously denote H.

18. Derivatives cyclohexylmethyl according to claim 1 or 3 in which R12denotes a phenyl residue, which is not substituted or monogamist substituents from the group comprising F, Cl, Br, NO2, OCH3, methyl, ethyl, propyl, butyl and tert-butyl.

19. Substituted derivatives of cyclohexylmethyl according to claim 1 or 3 in which R13denotes a saturated, branched or non-branched C1-C8-alkyl, which is not substituted or odnosnie substituents from the group comprising C1-C6-alkyl, O-benzyl, phenyl, O-phenyl, and O-phenyl substituted by F or Cl; C5-C10-cycloalkyl, which is not substituted or odnosnie by phenyl, and phenyl substituted by F or Cl, C6-C10-aryl or 5-is certain heteroaryl residue, containing 1-3 heteroatoms in the ring selected from N, O, and S, which may be condensed with a benzene ring, and the specified C6-C10is aryl or heteroaryl residue, which contain 1-5 substituents from the group comprising F, Cl, CN, NO2, pyridyl, thienyl, (CH2)O-C1-C6-alkyl, phenyl, substituted or unsubstituted by one or two F or Cl, dihydrobenzofuran, C1-C4-alkyl straight or branched chain containing one or more substituents selected from the group comprising F, Cl, S-phenyl or O-phenyl, each of which is substituted by F or Cl, or C1-C6-alkyl; S-C1-C6-alkyl, SO2phenyl, unsubstituted or substituted with one F or Cl, C3-C6-cycloalkyl attached through a bridging group C1-C4-alkyl, SO2C1-C6-alkyl straight or branched chain, or denotes thienyl attached via C1-C4is an alkyl chain, phenyl containing one Deputy, and the Deputy is chosen from the group comprising F, or Cl, or OC1-C4-alkyl.

20. Substituted derivatives of cyclohexylmethyl according to claim 20, in which R13denotes benzyl, benzothiazyl, 1-(4-chlorophenyl)cyclopentyl, 4-propylphenyl, 3-cyanophenyl, 3-chlorophenyl, 5-chloro-4-methoxythiophene-3-yl, 3-fluoro-5-triptoreline, 4-fluoro-5-triptoreline, 2-thienyl, 3,5-dihl henil, 2,4,5-tryptophanyl, 3-bromophenyl, 4-were, 3-methoxyphenyl, 2-tert-butyl-5-methylpyrazole-3-yl, 2,4-acid, 3-triptoreline, 3,5-differenl, 2-fluoro-5-triptoreline, 4-Chlorobenzyl, 2-methoxyphenyl, 2-methylsulfonyl-3-pyridyl, 3,4,5-trimethoxyphenyl, 2-ethylsulfinyl-3-pyridyl, 2-methyl-5-phenylfuro-3-yl, tert-butylphenyl, 2-(4-chlorophenylsulfonyl)-3-pyridyl, 2-perfoliate-3-pyridyl, 3-chloro-4-(sulfonyl-2-propyl)thiophene-2-yl, 5-methylisoxazol-3-yl, 5-bromo-3-pyridyl, naphthyl, 2-methyl-5-(4-chlorophenyl)furan-3-yl, 4-(4-chlorophenylsulfonyl)-3-methylthiophene-2-yl, 1-phenylpropyl, substituted, 2-phenylthiazol-4-yl, 4-methyl-2-phenylthiazol-5-yl, 2-(2,3-dihydrobenzofuran-5-yl)thiazol-4-yl, 3-were, 3-chloro-4-methylsulfonylmethane-2-yl, matiltan, 4-bromo-2-ethyl-5-methylpyrazole-3-yl, 2,5-dimethylphenol, 5-pyridine-2-althofen, 3-chloro-4-forfinal, cyclohexyl, 3-nitrophenyl, 2,5-differenl, 2,6-differenl, 2-trifluoromethyl-5-forfinal, 2-bromophenyl, cyclopentyl, benzothiadiazole, 2-were 3-methoxybenzyl, 2,4,6-trichlorophenyl, 2-chlorophenyl, 3,5-dinitrophenyl, 4-cyanophenyl, 2,4-dichloro-5-forfinal, 2-chloro-3-pyridyl, 4-nitrophenyl, 2,3,4,5,6-pentafluorophenyl, 3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl, 5-chloro-4-methylthiophene-3-yl, 4-forfinal, 4-chlorophenyl, 2-forfinal, 3-were 3-bromophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 4-cyanophenyl, 2,4-differenl, 2,4-dichlorophenyl, 2,4-dichloro-5-forfinal, 2-chloropyridin-3-yl, 3,5-dime is oxetanyl, 2,6-acid, 2,3,6-tryptophanyl, 2-(4-chlorophenoxy)-3-pyridyl, 3,4-differenl, 2-(2,3-dihydrobenzofuran-5-yl)-4-methylthiazole-5-yl, 3-metronidazole, 3-phenyloxazolyl, 3-cyclopropylmethoxy, 3-methoxyethoxymethyl or 2,4-acid.

21. Substituted derivatives of cyclohexylmethyl according to claim 1 from a group that includes
(16) the reaction of 4-(dimethylaminomethyl)cyclohexanone,
(17) 4-(dimethylaminophenyl)cyclohexylamine,
(18) the reaction of 4-[dimethylamino-(4-forfinal)methyl]cyclohexanone,
(19) 4-[dimethylamino-(4-forfinal)methyl]cyclohexylamine,
(20) the reaction of 4-[dimethylamino-(3-forfinal)methyl]cyclohexanone,
(21) 4-[dimethylamino-(3-forfinal)methyl]cyclohexylamine,
(22) the reaction of 4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexanone,
(23) 4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylamine,
(24) the reaction of 4-(dimethylaminopropan-2-ylmethyl)cyclohexanone,
(25) 4-(dimethylaminopropan-2-ylmethyl)cyclohexylamine,
(26) the oxime of 4-(1-dimethylamino-3-phenylpropyl)cyclohexanone,
(27) 4-(1-dimethylamino-3-phenylpropyl)cyclohexylamine,
(29) the reaction of 4-(dimethylaminophenyl)cyclohexanecarboxaldehyde,
(30) [(4-aminoethylthiomethyl)phenylmethyl]dimethylamine,
(32) the reaction of 4-[dimethylamino-(4-forfinal)methyl]cyclohexanecarboxaldehyde,
(33) [(4-aminoethylthiomethyl)-(4-forfinal)methyl]dimethylamine,
(35) the reaction of 4-[dimethylamino-(3-forfinal)methyl]cyclohe is cannabalized,
(36) [(4-aminoethylthiomethyl)-(3-forfinal)methyl]dimethylamine,
(38) the reaction of 4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexanecarboxaldehyde,
(39) [(4-aminoethylthiomethyl)-(4-chlorophenyl)methyl]dimethylamine,
(41) the reaction of 4-(dimethylaminopropan-2-ylmethyl)cyclohexanecarboxaldehyde,
(42) [(4-aminoethylthiomethyl)thiophene-2-ylmethyl]dimethylamine,
(44) the oxime of 4-(1-dimethylamino-3-phenylpropyl)cyclohexanecarboxaldehyde,
(45) [1-(4-aminoethylthiomethyl)-3-phenylpropyl]dimethylamine,
(47) the oxime [4-(dimethylaminophenyl)cyclohexyl]acetaldehyde,
(48) 2-[4-(dimethylaminophenyl)cyclohexyl]ethylamine,
(50) the reaction of {4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}acetaldehyde,
(51) 2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethylamine,
(53) the reaction of {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}acetaldehyde,
(54) 2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethylamine,
(56) the reaction of {4-[dimethylamino-(4-chlorophenyl)methyl]cyclohexyl}acetaldehyde,
(66) 2-{4-[dimethylamino-(4-chlorophenyl)methyl]cyclohexyl}ethylamine,
(68) the reaction of 2-(4-((dimethylamino)(thiophene-2-yl)methyl)cyclohexyl)acetaldehyde,
(69) 2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethylamine,
(71) the oxime [4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]acetaldehyde,
(72) {1-[4-(2-amino-ethyl)cyclohexyl]-3-phenylpropyl}dimethylamine,
(111) 4-[dimethylaminomethyl]cyclohexanol,
(112) 4-[demeti the amino-(4-forfinal)methyl]cyclohexanol,
(113) 4-[dimethylamino-(3-forfinal)methyl]cyclohexanol,
(114) 4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexanol,
(115) 4-(dimethylaminopropan-2-ylmethyl)cyclohexanol,
(116) 4-(1-dimethylamino-3-phenylpropyl)cyclohexanol,
(117) [4-(dimethylaminophenyl)cyclohexyl]methanol,
(118) {4-[dimethylamino-(4-forfinal)methyl]cyclohexyl} methanol,
(119) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}methanol,
(120) {4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}methanol,
(121) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]methanol,
(122) [4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]methanol,
(124) ethyl ester [4-(dimethylaminophenyl)cyclohexyl] acetic acid,
(125) 2-[4-(dimethylaminophenyl)cyclohexyl]ethanol,
(126) ethyl ester {4-[dimethylamino-(4-forfinal)methyl]cyclohexylidene}acetic acid,
(127) ethyl ester {4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}acetic acid,
(128) 2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethanol,
(129) ethyl ester {4-[dimethylamino-(3-forfinal)methyl]cyclohexylidene}acetic acid,
(130) ethyl ester {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl} acetic acid,
(131) 2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethanol,
(134) 3-[4-(dimethylaminophenyl)cyclohexyl]propane-1-ol,
(137) 3-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}propane-1-ol,
(140) 3-{4-[dimethylene is o-(3-forfinal)methyl]cyclohexyl}propane-1-ol,
(142) ethyl ester of 3-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]propionic acid,
(143) 3-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]propane-1-ol,
(73) 1-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-3-(naphthalene-1-yl)urea,
(74) hydrochloride 1-(2,4-differenl)-3-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)urea,
(75) of the hydrochloride of 1-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-3-(3-(trifluoromethyl)phenyl)urea,
(76) hydrochloride 1-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-3-(2-nitrophenyl)urea,
(77) of the hydrochloride of 1-(3-bromophenyl)-3-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)urea,
(78) hydrochloride 1-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-3-phenylacetone,
(79) 1-benzyl-3-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)urea,
(80) 1-cyclohexyl-3-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)urea,
(81) 1-(4-bromophenyl)-3-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)urea,
(82) 1-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-3-(4-methoxyphenyl)urea,
(83) of the hydrochloride of N-(2-(1H-indol-3-yl)ethyl)-4-((dimethylamino)(phenyl)methyl)cyclohexanamine,
(84) of the hydrochloride of 4-((dimethylamino)(phenyl)methyl)-N-penicillinaugmentin,
(85) dihydrochloride 4-((dimethylamino)(phenyl)methyl)-N-(3-phenylpropyl)cyclohexanamine,
(86) of the hydrochloride of N-benzyl-4-((dimethylamino)(phenyl)methyl)cyclohexanamine,
(87) of the hydrochloride of 4-((dimethylamino)(phenyl)methyl)-N-(4-phenylbutyl)CEC is hexanamine,
(88) of the hydrochloride of N-(1-(1H-indol-3-yl)propan-2-yl)-4-((dimethylamino)(phenyl)methyl)cyclohexanamine,
(89) of the hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-4-methoxybenzylamine,
(90) dihydrochloride 4-((dimethylamino)(phenyl)methyl)-N-(4-methoxybenzyl)cyclohexanamine,
(91) of the hydrochloride of 4-((dimethylamino)(phenyl)methyl)-N-(4-terbisil)cyclohexanamine,
(92) of the hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzenamine,
(94) of the hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzamide,
(103) of the hydrochloride of N-benzyl-N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-4-fermentated,
(104) of the hydrochloride of N-benzyl-N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzamide,
(106) hydrochloride 4-chloro-N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzosulfimide,
(107) of the hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-4-methoxybenzenesulfonamide,
(108) of the hydrochloride of 4-tert-butyl-N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzosulfimide,
(109) of the hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)-2-nitrobenzenesulfonamide,
(110) hydrochloride of N-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)benzosulfimide,
(144) of the hydrochloride of 4-((benzyloxy)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
(145) of the hydrochloride of 4-((4-forbindelse)cyclohexyl)-N,N-dimethyl(phenyl)methanamine,
(146) of the hydrochloride of N,N-dimethyl(4-penitenziagite)(phenyl)methanes is on,
(147) of the hydrochloride of 1-benzyl-4-((dimethylamino)(phenyl)methyl)cyclohexanol,
(148) of the hydrochloride of 4-((dimethylamino)(phenyl)methyl)-1-(4-terbisil)cyclohexanol,
(149) 1-(2,5-acid)-4-((dimethylamino)(phenyl)methyl)cyclohexanol,
(151) 4-(dimethylaminophenyl)-1-(4-fluoro-3-were)cyclohexanol,
(152) 1-benzyl-4-[dimethylamino-(3-forfinal)methyl]cyclohexanol,
(153) 4-[dimethylamino-(3-forfinal)methyl]-1-fenetylline,
(154) 4-[dimethylamino-(3-forfinal)methyl]-1-pentylcyclohexane,
(155) 1-(3,5-dichlorophenyl)-4-[dimethylamino-(3-forfinal)methyl]cyclohexanol,
(156) 4-[dimethylamino-(3-forfinal)methyl]-1-(3-methoxybenzyl)cyclohexanol,
(157) 1-(4-chloro-3-triptoreline)-4-[dimethylamino-(3-forfinal)methyl]cyclohexanol,
(158) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-phenylcyclohexanol,
(159) 1-benzyl-4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexanol,
(160) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(4-fluoro-3-were)cyclohexanol,
(161) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-orthotricyclene,
(162) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(4-forfinal)cyclohexanol,
(163) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-fenetylline,
(164) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(3-methoxyphenyl)cyclohexanol,
(165) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-paracrystalline,
(166) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(3,5-differenl)cyclohexanol,
(167) -butyl-4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexanol,
(168) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-sexycollegegirl,
(169) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-pentylcyclohexane (diastereoisomer),
(170) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-pentylcyclohexane (diastereoisomer),
(171) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(3-forfinal)cyclohexanol,
(172) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(4-terbisil)cyclohexanol,
(173) 4-[(4-chlorophenyl)dimethylaminomethyl]-1-(3-methoxybenzyl)cyclohexanol,
(183) [4-(dimethylaminophenyl)cyclohexyl]amide benzo[b]thiophene-3-carboxylic acid,
(184) [4-(dimethylaminophenyl)cyclohexyl]amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(185) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-4-propylbenzamide,
(186) 3-cyano-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]benzamide,
(187) 3-chloro-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(188) [4-(dimethylaminophenyl)cyclohexyl]amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(189) of 3,4-dichloro-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(190) N-[4-(dimethylaminophenyl)cyclohexyl]-3-fluoro-5-cryptomelane,
(191) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(192) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-4-fluoro-3-cryptomelane,
(193) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide thiophene-2-carboxylic acid,
(194 3,5-dichloro-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]benzamide,
(195) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(196) N-[4-(dimethylaminophenyl)cyclohexyl]-2,4,5-triterpenoid,
(197) 3-bromo-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(198) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-4-methylbenzamide,
(199) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-3-methoxybenzamide,
(201) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide of 2-tert-butyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(202) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-2,4-dimethoxybenzamide,
(203) N-[4-(dimethylaminophenyl)cyclohexyl]-3-cryptomelane,
(204) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl} - for 3,5-diflorasone,
(205) N-[4-(dimethylaminophenyl)cyclohexyl]-2-fluoro-5-cryptomelane,
(207) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-2-methoxybenzamide,
(208) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-2-methylsulfonylmethane,
(209) 3,4-dichloro-N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}benzamide,
(210) N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]-4-fluoro-3-cryptomelane (diastereoisomer),
(211) {4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(212) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-3,4,5-trimethoxybenzamide,
(213) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexa the]-2-metilsulfonilmetane,
(214) [4-(dimethylaminophenyl)cyclohexyl]amide of 2-methyl-5-phenylfuro-3-carboxylic acid,
(216) N-[4-(dimethylaminophenyl)cyclohexyl]-2,4-dimethoxybenzamide,
(217) 4-tert-butyl-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(218) 2-(4-chlorophenylsulfonyl)-N-[4-(dimethylaminopropan-2-ylmethyl)-cyclohexyl]nicotinamide,
(220) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-2-paratoluidine,
(221) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide of 3-chloro-4-(propane-2-sulfonyl)thiophene-2-carboxylic acid,
(223) [4-(dimethylaminophenyl)cyclohexyl]amide of 2-tert-butyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(224) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide 5-methylisoxazol-3-carboxylic acid,
(225) 5-bromo-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]nicotinamide,
(226) [4-(dimethylaminophenyl)cyclohexyl]amide naphthyl-1-carboxylic acid,
(227) N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]-4-fluoro-3-cryptomelane (diastereoisomer),
(229) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide 5-(4-chlorophenyl)-2-methylfuran-3-carboxylic acid,
(231) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide benzo[b]thiophene-2-carboxylic acid,
(232) [4-(dimethylaminophenyl)cyclohexyl]amide 5-(4-chlorophenyl)-2-methylfuran-3-carboxylic acid,
(233) [4-(dimethylaminophenyl)cyclohexyl]amide 4-(4-chlorobenzenesulfonyl)3-methylthiophene-2-carboxylic acid,
(235) 5-bromo-N-[4-(dimethylaminophenyl)cyclohexyl]nicotinamide,
(236) [4-(dimethylaminophenyl)cyclohexyl]amide adamantane-1-carboxylic acid,
(237) [4-(dimethylaminophenyl)cyclohexyl]amide 2-phenylthiazol-4-carboxylic acid,
(238) [4-(dimethylaminophenyl)cyclohexyl]amide 4-methyl-2-phenylthiazol-5-carboxylic acid,
(239) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide of 2-(2,3-dihydrobenzofuran-5-yl)thiazole-4-carboxylic acid,
(241) 3-chloro-N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]benzamide,
(242) N-[4-(dimethylaminophenyl)cyclohexyl]-4-methylbenzamide,
(243) 3,5-dichloro-N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}benzamide,
(244) N-[4-(dimethylaminophenyl)cyclohexyl]-2,3,6-triterpenoid,
(245) [4-(dimethylaminophenyl)cyclohexyl]amide thiophene-2-carboxylic acid (diastereoisomer),
(247) [4-(dimethylaminophenyl)cyclohexyl]amide of 2-tert-butyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(248) N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]-3-methylbenzamide,
(249) [4-(dimethylaminophenyl)cyclohexyl]amide thiophene-2-carboxylic acid (diastereoisomer),
(252) [4-(dimethylaminophenyl)cyclohexyl]amide of 3-chloro-4-methanesulfonamide-2-carboxylic acid,
(253) [4-(dimethylaminophenyl)cyclohexyl]amide 4-(4-chlorobenzenesulfonyl)-3-methylthiophene-2-carboxylic acid,
(255) N-[4-(dimethylaminophenyl)cyclohex the yl]-2-thiophene-2-ylacetamide,
(256) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 4-methyl-2-phenylthiazol-5-carboxylic acid,
(257) 2-(4-chlorophenoxy)-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]nicotinamide,
(258) N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]-4-perbenzoic,
(259) 5-bromo-N-[4-(dimethylaminophenyl)cyclohexyl]nicotinamide,
(260) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide of 4-bromo-2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(261) 3-cyano-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(262) N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-4-perbenzoic,
(263) 3-bromo-N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}benzamide,
(264) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 2-phenylthiazol-4-carboxylic acid,
(265) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 2,5-dimethylfuran-3-carboxylic acid,
(266) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 2-methyl-5-phenylfuro-3-carboxylic acid,
(267) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 5-pyridin-2-althofen-2-carboxylic acid,
(268) [4-(dimethylaminophenyl)cyclohexyl]amide of 4-bromo-2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(269) 3-chloro-N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}-4-perbenzoic,
(270) 3,4-dichloro-N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}benzamide,
(271) N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-2,4,5-trip arbennig,
(272) [4-(dimethylaminophenyl)cyclohexyl]amide cyclohexanecarbonyl acid,
(275) N-[4-(dimethylaminophenyl)cyclohexyl]-3-nitrobenzamide,
(276) N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]-2,5-diflorasone,
(277) 3-bromo-N-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]benzamide,
(278) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}-2,6-diflorasone,
(279) [4-(dimethylaminophenyl)cyclohexyl]amide 2,5-dimethylfuran-3-carboxylic acid,
(280) 3-chloro-N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-4-perbenzoic,
(281) N-[4-(dimethylaminophenyl)cyclohexyl]-5-fluoro-2-cryptomelane,
(282) [4-(dimethylaminophenyl)cyclohexyl]amide 5-methylisoxazol-3-carboxylic acid,
(283) [4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]amide of 2-(2,3-dihydrobenzofuran-5-yl)-4-methylthiazole-5-carboxylic acid,
(285) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 5-(4-chlorophenyl)-2-methylfuran-3-carboxylic acid,
(286) 2-bromo-N-[4-(dimethylaminophenyl)cyclohexyl]benzamide,
(287) N-[4-(dimethylaminophenyl)cyclohexyl]-2,6-dimethoxybenzamide,
(288) [4-(dimethylaminophenyl)cyclohexyl]amide cyclopentanecarbonyl acid,
(289) [4-(dimethylaminophenyl)cyclohexyl]amide of 2-(2,3-dihydrobenzofuran-5-yl)thiazole-4-carboxylic acid,
(290) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide benzo[1,2,5]thiadiazole-5-carboxylic what islote,
(291) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2-thiophene-2-ylacetamide,
(292) [4-(dimethylaminophenyl)cyclohexylmethyl]amide benzo[b]thiophene-3-carboxylic acid,
(293) [4-(dimethylaminophenyl)cyclohexylmethyl]amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(294) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-3,4-diflorasone (less polar diastereoisomer),
(296) 2-bromo-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]benzamide,
(299) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-2-methylsulfonylmethane,
(300) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2,6-dimethoxybenzamide,
(302) [4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]amide benzo[b]thiophene-3-carboxylic acid,
(303) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(305) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2-methoxybenzamide,
(307) 3-bromo-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]benzamide,
(308) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-3-fluoro-5-cryptomelane,
(310) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-2-metilsulfonilmetane,
(313) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2,6-diflorasone,
(314) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide benzo[b]thiophene-3-carboxylic acid,
(315) N-{4-[(4-chlorp the Nile)dimethylaminomethyl]cyclohexylmethyl}-2-methylsulfonylmethane,
(316) N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}-2-thiophene-2-ylacetamide,
(317) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-2-methylbenzamide (diastereoisomer),
(318) [4-(dimethylaminophenyl)cyclohexylmethyl]amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(325) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-2-methylbenzamide (diastereoisomer),
(326) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-3-cryptomelane (diastereoisomer),
(327) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(328) [4-(dimethylaminophenyl)cyclohexylmethyl]amide thiophene-2-carboxylic acid,
(329) 3,5-dichloro-N-[4-(dimethylaminophenyl)cyclohexylmethyl]benzamide,
(330) {4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}amide 2-methyl-5-phenylfuro-3-carboxylic acid,
(331) 3-chloro-N-[4-(dimethylaminophenyl)cyclohexylmethyl]benzamide,
(333) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-3-cryptomelane (more polar diastereoisomer),
(334) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide thiophene-2-carboxylic acid (diastereoisomer),
(335) [4-(dimethylaminophenyl)cyclohexylmethyl]amide 2-phenylthiazol-4-carboxylic acid,
(336) {4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}amide benzo[b]thiophene-3-carboxylic acid (diastereoisomer),
(337) N-{4-[dimethylamino-(-forfinal)methyl]cyclohexylmethyl}-2-paratoluidine,
(338) 2,4,6-trichloro-N-[4-(dimethylaminophenyl)cyclohexylmethyl]benzamide,
(339) [4-(dimethylaminophenyl)cyclohexylmethyl]amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(340) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide thiophene-2-carboxylic acid (diastereoisomer),
(343) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-2-thiophene-2-ylacetamide,
(344) {4-[dimethylamino-(4-forfinal)methyl]cyclohexylmethyl}amide benzo[b]thiophene-3-carboxylic acid,
(345) [4-(dimethylaminophenyl)cyclohexylmethyl]amide of 2-methyl-5-phenylfuro-3-carboxylic acid,
(347) 3-cyano-N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]benzamide,
(350) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-4-fluoro-3-cryptomelane,
(351) N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}-2-metilsulfonilmetane,
(352) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2-paratoluidine (diastereoisomer),
(353) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide 2-methyl-5-phenylfuro-3-carboxylic acid,
(354) of 2-chloro-N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}benzamide,
(355) 2-chloro-N-[4-(dimethylaminophenyl)cyclohexylmethyl]nicotinamide,
(356) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-4-propylbenzamide,
(357) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-3,4-diflorasone (more fields is hydrated diastereoisomer),
(358) 3-bromo-N-[4-(dimethylaminophenyl)cyclohexylmethyl]benzamide,
(359) N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexylmethyl}-2-thiophene-2-ylacetamide,
(360) 2-(4-chlorophenoxy)-N-[4-(dimethylaminophenyl)cyclohexylmethyl]nicotinamide (less polar diastereoisomer),
(361) 2,4-dichloro-N-[4-(dimethylaminophenyl)cyclohexylmethyl]benzamide,
(362) N-[4-(dimethylaminophenyl)cyclohexylmethyl]-3-methylbenzamide,
(363) 2-bromo-N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}benzamide,
(364) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-3-cryptomelane,
(365) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide 2-phenylthiazol-4-carboxylic acid,
(366) [4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]amide of 2-tert-butyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(367) [4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]amide of 3-chloro-4-(propane-2-sulfonyl)thiophene-2-carboxylic acid,
(368) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-2-methoxybenzamide,
(369) N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}-3-cryptomelane,
(370) {4-[dimethylamino-(4-forfinal)methyl]cyclohexylmethyl}amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(371) 3,5-dichloro-N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}benzamide,
(372) {4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}amide benzo[b]thiophene-3-carbon is howling acid (diastereoisomer),
(373) {4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}amide 2-methyl-5-phenylfuro-3-carboxylic acid,
(374) 2-(4-chlorophenylsulfonyl)-N-[4-(dimethylaminophenyl)-cyclohexylmethyl]nicotinamide,
(375) [4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]amide of 4-bromo-2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(376) {4-[dimethylamino-(4-forfinal)methyl]cyclohexylmethyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(379) [4-(dimethylaminophenyl)cyclohexylmethyl]amide 5-methylisoxazol-3-carboxylic acid,
(380) [4-(1-dimethylamino-3-phenylpropyl)cyclohexylmethyl]amide benzo[b]thiophene-3-carboxylic acid,
(381) N-{4-[dimethylamino-(4-forfinal)methyl]cyclohexylmethyl}-2-methylsulfonylmethane,
(382) N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}-2-paratoluidine,
(383) 2-(4-chlorophenoxy)-N-[4-(dimethylaminophenyl)cyclohexylmethyl]nicotinamide (diastereoisomer),
(384) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-2-methylbenzamide,
(385) {4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}amide 5-methylisoxazol-3-carboxylic acid,
(386) 5-bromo-N-[4-(dimethylaminophenyl)cyclohexylmethyl]nicotinamide,
(388) N-{4-[dimethylamino-(3-forfinal)methyl]cyclohexylmethyl}-2-metilsulfonilmetane,
(389) N-[4-(dimethylaminopropan-2-ylmethyl)cyclohexylmethyl]-2-paratoluidine (less polar dust reamer),
(390) [4-(dimethylaminophenyl)cyclohexylmethyl]amide of 4-bromo-2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid,
(392) N-[4-(dimethylaminophenyl)cyclohexylmethyl]for 3,5-dinitrobenzamide,
(393) N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}-3-methoxybenzamide,
(394) 2-bromo-N-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexylmethyl}benzamide,
(395) 2-bromo-N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)benzamide,
(396) 2-bromo-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)benzamide,
(397) 3-chloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide (diastereoisomer),
(398) 3-chloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide (diastereoisomer),
(399) 3-chloro-N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)benzamide,
(400) 3-chloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)benzamide (diastereoisomer),
(401) 3-chloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)benzamide (diastereoisomer),
(402) of 2-chloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(403) of 2-chloro-N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)benzamide,
(404) of 2-chloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)benzamide,
(405) 4-chloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(406) 4-chloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)benzamide,
(407) N-{2-[4-(dimethylaminophenyl)cyclohe the forces]ethyl}-4-perbenzoic,
(408) N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)-4-perbenzoic,
(409) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-4-perbenzoic,
(410) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2-perbenzoic,
(411) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-2-perbenzoic,
(412) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-3-methylbenzamide,
(413) 2,6-dichloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(414) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2-methoxybenzamide,
(415) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-2-methoxybenzamide,
(416) 3,4-dichloro-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(417) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2-methylbenzamide (diastereoisomer),
(418) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2-methylbenzamide (diastereoisomer),
(419) N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)-2-methylbenzamide,
(420) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-2-methylbenzamide,
(421) 4-cyano-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(422) 3-chloro-N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)benzamide (diastereoisomer),
(423) 3-chloro-N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)benzamide (diastereoisomer),
(424) 3-chloro-N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}Bentham the d,
(425) of 2-chloro-N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}benzamide,
(426) N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}-4-perbenzoic,
(427) N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)-2-perbenzoic,
(428) N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]-ethyl}-2-perbenzoic,
(429) N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)-3-methylbenzamide,
(430) N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}-3-methylbenzamide,
(431) of 2,6-dichloro-N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}benzamide,
(432) N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)-2-methoxybenzamide,
(433) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl} - for 3,5-diflorasone,
(434) N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl) - for 3,5-diflorasone,
(435) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl) - for 3,5-diflorasone,
(436) N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)-2,4-diflorasone,
(437) of 2,4-dichloro-N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)-5-perbenzoic,
(438) of 2,4-dichloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-5-perbenzoic (diastereoisomer),
(439) of 2,4-dichloro-N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-5-perbenzoic (diastereoisomer),
(440) 2,4-dichloro-N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}-5-perbenzoic,
(441) of 2-chloro-N-(2-{4-[(4-chlorophenyl)di is ethylaminomethyl]cyclohexyl}ethyl) - nicotinamide,
(442) (2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)amide naphthalene-2-carboxylic acid,
(443) N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}-4-propylbenzamide,
(444) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-3,4-diflorasone,
(445) N-(2-{4-[(4-chlorophenyl)dimethylaminomethyl]cyclohexyl}ethyl)-3,4-diflorasone,
(446) N-{2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}-3,4-diflorasone,
(447) N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl)-3-methoxybenzamide,
(448) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2,2-diphenylacetamide,
(449) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 1-(4-chlorophenyl)cyclopentanecarboxylic acid,
(452) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide thiophene-2-carboxylic acid,
(457) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide benzo[b]thiophene-2-carboxylic acid,
(458) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-4-nitrobenzamide,
(459) 3-bromo-N-(2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}-ethyl)benzamide,
(460) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2,3,4,5,6-pentafluorobenzene,
(461) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2,6-diflorasone,
(462) N-(2-{4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}ethyl)-2,6-diflorasone,
(463) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 2-phenylthiazol-4-carboxylic acid,
(464) (2-{4-[Dima is ylamino-(4-forfinal)methyl]cyclohexyl}ethyl) - amide 2-phenylthiazol-4-carboxylic acid,
(465) {2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}amide benzo[b]thiophene-3-carboxylic acid,
(466) N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}-2-methylsulfonylmethane,
(467) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 2-methyl-5-phenylfuro-3-carboxylic acid,
(468) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 2-(2,3-dihydrobenzofuran-5-yl)thiazole-4-carboxylic acid,
(469) {2-[4-(dimethylaminopropan-2-ylmethyl)cyclohexyl]ethyl}amide 3-(2,6-dichlorophenyl)-5-methylisoxazol-4-carboxylic acid,
(470) 2-(4-chlorophenylsulfonyl)-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}nicotinamide (diastereoisomer),
(471) 2-(4-chlorophenylsulfonyl)-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}nicotinamide (diastereoisomer),
(472) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide benzo[1,2,3]thiadiazole-5-carboxylic acid,
(473) 5-bromo-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}nicotinamide,
(474) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(475) (2-{4-[dimethylamino-(4-forfinal)methyl]cyclohexyl}ethyl) - amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(476) {2-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]ethyl}amide 5-chloro-4-methoxythiophene-3-carboxylic acid,
(477) 3-cyano-N-{2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}benzamide,
(478) N-{2-[4-(dimethylaminophenyl)cyclohexa is]ethyl}-2,4-dimethoxybenzamide,
(479) 2-chloro-N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)benzamide,
(480) N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)-4-perbenzoic,
(481) N-(2-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)ethyl)-4-perbenzoic,
(482) N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)-2-perbenzoic,
(483) N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)-3-methylbenzamide,
(484) N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)-2-methoxybenzamide,
(485) N-(2-(4-((dimethylamino)(phenyl)methyl)cyclohexyl)ethyl) - for 3,5-dimethoxybenzamide,
(486) N-((4-((dimethylamino)(3-forfinal)methyl)cyclohexyl)methyl)-2,6-dimethoxybenzamide,
(487) N-((4-((dimethylamino)(phenyl)methyl)cyclohexyl)methyl)-2,4-diflorasone,
(488) N-((4-((dimethylamino)(thiophene-2-yl)methyl)cyclohexyl)methyl)-3-methoxybenzamide,
(489) N-((4-((dimethylamino)(thiophene-2-yl)methyl)cyclohexyl)methyl)-3,4,5-trimethoxybenzamide,
(490) 4-((dimethylamino)(phenyl)methyl)-1-(4-fluoro-3-were)cyclohexanol,
(493) N-(4-methoxyphenyl)-2-(4-(piperidine-1-yl(paratool)methyl)cyclohexylidene)ndimethylacetamide,
(494) N-phenethyl-2-(4-(piperidine-1-yl(paratool)methyl)cyclohexylidene)ndimethylacetamide,
(495) 2-(4-(2-phenyl-1-(pyrrolidin-1-yl)ethyl)cyclohexylidene)-N-(pyridine-2-ylmethyl)ndimethylacetamide,
(496) N-benzyl-N-methyl-2-(4-(piperidine-1-yl(paratool)methyl)cyclohexylidene)ndimethylacetamide,
(497) [4-(dimethylaminophenyl)cyclohexyl]amide of 3-thiophene-2-yl-[1,2,4]oxadiazol-5-carbon is th acid,
(498) {2-[4-(dimethylaminophenyl)cyclohexyl]ethyl}amide 3-methyl-[1,2,4]oxadiazol-5-carboxylic acid,
(499) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 3-phenyl-[1,2,4]oxadiazol-5-carboxylic acid,
(500) {4-[dimethylamino-(3-forfinal)methyl]cyclohexyl}amide 3-cyclopropylmethyl-[1,2,4]oxadiazol-5-carboxylic acid and
(501) {2-[4-(1-dimethylamino-3-phenylpropyl)cyclohexyl]ethyl}amide 3-methoxymethyl-[1,2,4]oxadiazol-5-carboxylic acid.

22. The method of obtaining derivatives of cyclohexylmethyl according to claims 1 to 21, in which R1means (CH2)mCHN-OH or - (CH2)nNH2consisting in that a ketone of the formula G, respectively, the aldehyde of the formula H

interaction with hydroxylamine hydrochloride in an organic solvent, for example ethanol, and adding a base, for example a basic ion exchanger type amberlist, converted into oximes of General formula K, of which the interaction with a reducing agent, for example with LiAlH4get amines of General formula L

moreover, in the above structural formulas
R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or accession is hydrated through C 1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6.

23. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R1means (CH2)nNHC(O)R13consists in the fact that amines of General formula L

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6,
put the combination with a carboxylic acid, optionally adding reagents to activate the functional carboxypropyl for translation in connection equivalent of carboxylic acid such as the acid chloride acid.

24. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R1means (CH2)nNHC(O)NRl0Rllaccordingly, (CH2)nNHC(S)NR10Rllconsists in the fact that amines of General formula L

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or R4and R5together (CH2)3-6,
subjected, optionally in the presence of at least one base, to interact with the appropriate isocyanates of General formula R10-N=C=O, respectively isothioscyanates General formula R10-N=C=S obtaining compounds of General formula I, where R1means (CH2)nNHC(O)NR10R11or (CH2)nNHC(S)NR10R11and R11denotes H, and this compound is subjected, optionally in the presence of at least one base, the interaction with the compound of General formula LG-R11where LG denotes a leaving group, and R11has the above values, with the exception of hydrogen, to obtain the compounds of General formula I, in which R1means (CH2)nNHC(O)NR10R11or (CH2)nNHC(S)NR10R11where R11doesn't mean H.

25. Way obtained the I derivative cyclohexylmethyl according to claim 1, in which R1means attached via saturated or unsaturated C1-C3-alkyl group, C(O)OR9or R1and R2together denote the groupnamely, that the ether phosphonooxy acid, preferably timetravel or tritherapy ether phosphonooxy acid, is first subjected to interaction with a strong base, preferably tert-butyl potassium, sodium hydride or butyllithium, and then with a ketone of General formula G or aldehyde of the formula H

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or R4and R5together (CH2)3-6,
and, if necessary, hydrolyzing esters at room temperature or slightly elevated temperature acceptable aqueous alkaline solution, preferably a solution of potassium hydroxide or lithium hydroxide, to obtain the corresponding carboxylic acids or restore the pour in the double bond, preferably by hydrogenation in the heterogeneous catalysis by palladium or platinum catalysts in each case at a temperature ranging from room temperature up to 60°C and a hydrogen pressure ranging from 1 to 6 bar, most preferably at room temperature and at a hydrogen pressure of 2 to 3 bar on palladium on coal, then the above by hydrolyzing esters, which can thus treatment with reducing agent, such as LiAlH4to restore to the corresponding alcohols.

26. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R1means (CH2)nC(O)NR10R11consists in the fact that the carboxylic acid A.25 in the presence of dehydrating means, such as sodium sulfate or magnesium, phosphorus oxide, or after conversion into the acid chloride or active ester is subjected to interaction with a primary or secondary amine.

27. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R1means (CH2)nOR8in which R8matter specified in claim 1, the interaction of the ketone of formula G or aldehyde of the formula H

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected and the 5-membered, sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6,
with a reducing agent, e.g. sodium borohydride or recovery of ester obtained in A.25, with a reducing agent, such as LiAlH4, to obtain the corresponding alcohol, where R1represents (CH2)nOH, when you add a base, for example NaH, is subjected to the interaction with the compound of General formula R8Hal, where Hal preferably denotes Cl with obtaining the compounds in which R1(CH2)nOR8where R8does not denote H and has the values specified in claim 1.

28. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R1means (CH2)nOther6consisting in that a ketone of the formula G, respectively, the aldehyde of the formula H

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached caress 1-C4is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6,
dissolve in polar aprotic solvents, such as THF, and subjected to the interaction with the corresponding amines of General formula NH2R6when adding a suitable reducing agent such as sodium borohydride.

29. The method of obtaining derivatives of cyclohexylmethyl according to claim 1, in which R2denotes OH, and R1denotes unbranched, saturated, unsubstituted or one-deputizing C1-C8-alkyl, where the substituents are selected from =O, CO2C1-C4-alkyl, phenyl residue, unsubstituted or mono - or dvuhkamernyi halogen, or attached via C1-C4is an alkyl chain is unsubstituted or one - or dvuhkamernyi phenyl residue, which may contain as substituents halogen or OC1-C4-alkyl, interaction ketone of General formula G

where R3denotes a phenyl residue, unsubstituted or one-deputizing a halogen atom, or heteroaryl residue selected from 5-membered sulfur-containing heteroaryl, such as thienyl residue, or attached via C1-C is an alkyl group unsubstituted phenyl residue,
R4and R5independently of one another denote unsubstituted C1-C3-alkyl, or
R4and R5together (CH2)3-6,
put in an organic solvent, for example diethyl ether or THF, cooled to a temperature in the range from -30 to +10°C interaction with ORGANOMETALLIC compounds of the General formula R1aMgHal, where Hal denotes Cl or Br, or R1aLi to obtain compounds with a value of R1-non-branched saturated unsubstituted or one-deputizing C1-C8-alkyl, where the substituents are selected from =O, CO2C1-C4-alkyl; or is attached through the C1-C4is an alkyl chain is unsubstituted or one - or dvuhkamernyi phenyl residue, which may contain as substituents halogen or OC1-C4-alkyl or with the corresponding periodical in an organic solvent, such as THF, at a temperature in the range from -30 to 0°C is mixed with a solution of isopropylacrylamide and after stirring for at least 10 min to obtain the compounds where R1denotes a phenyl residue, unsubstituted or mono - or dvuhkamernyi halogen.

30. Drug, possess inhibitory activity against cocktail recipes. is s serotonin, norepinephrine or opioids and containing at least one substituted derivative of cyclohexylmethyl according to claim 1, optionally in the form of CIS - or TRANS-isomer or mixtures thereof, bases and/or salts with physiologically compatible acids, and optionally containing acceptable additives and/or auxiliary substances.

31. The use of substituted derivative of cyclohexylmethyl according to claim 1, optionally in the form of CIS - or TRANS-isomer or mixtures thereof, bases and/or salts with physiologically compatible acids, for preparing a medicinal product intended for analgesic treatment, especially in acute, neuropathic or chronic pain.

32. The use of substituted derivative of cyclohexylmethyl according to claim 1, optionally in the form of CIS - or TRANS-isomer or mixtures thereof, bases and/or salts with physiologically compatible acids, for preparing a medicinal product intended for the treatment of depression, urinary incontinence, diarrhea, and alcoholism.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formulae (I) and (III), as well as isomers or pharmaceutically acceptable salts thereof: where the values of radicals are given in claim 1 and 5. The invention also relates to a pharmaceutical composition based on said compounds, which has vanilloid receptor antagonist activity, use of said compounds to produce a medicinal agent for preventing or treating a condition which is associated with aberrant expression and/or aberrant activation of the vanilloid receptor. Described also is a method of producing a compound of formula III.

EFFECT: novel compounds which can be used as vanilloid receptor antagonists, for preventing or treating diseases are obtained and described.

40 cl, 281 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyridine derivatives of formula

wherein A, R1, R2, R3, R4, R5 and R6 are presented in the description, preparing and using them as pharmaceutically active compounds as immunomodulatory agents.

EFFECT: preparing the pharmaceutical composition showing agonist activity with respect to S1P1/EDG1 receptor and using it for prevention and treatment diseases or disorders associated with activated immune system.

20 cl, 244 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to heterocyclic compounds of formula ,

wherein X2 represents residue C-Z-R2 or C-R3, wherein Z represents NH or S; R1 is selected from structures , and R2 and R3 have the values specified in cl.1 of the patent claim, or to their pharmaceutically acceptable salts. The invention also refers to a pharmaceutical composition, a series of specific compounds, application of the declared compounds and to an intermediate compound for preparing the compounds of formula (I).

EFFECT: compounds under the invention have affinity to muscarine receptors and can be used in treating, relieving and preventing diseases and conditions mediated by muscarine receptors.

13 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I

,

where A represents S or Se; B represents H or ; R1 represents aryl selected from the following structures:

R2 represents H or ; R3 represents H or C1-C8 alkyl; R4 and R5 independently represent H or C1-C8 alkyl; R6 represents H, C1-C8 alkyl, C2-C7 alkenyl, alkaline metal or alkaline earth metal; R11 and R12 independently represent H, C1-C8 alkyl or halogen; R21 represent H, halogen or C1-C7 alkyl; m and n independently represent integers having values 1-4; p represents an integer having a value of 1-5; q represents an integer having a value of 1-4; r represents an integer having a value of 1-3; s represents an integer having a value of 1-5; as an activator of peroxisome proliferator-activated receptor (PPAR) and its hydrate, solvate, stereoisomer and pharmaceutically acceptable salt, and to a pharmaceutical composition.

EFFECT: preparing an agent for muscle strengthening, an agent for memory improvement, a therapeutic agent for dementia and Parkinson's disease.

15 cl, 8 tbl, 348 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new thiophene derivatives of formula (I) where A is represented by *-CO-CH2CH2-, *-CO-CH=CH, where the asterisks indicate the link through which the formula (I) thiophene group is bound; R1 is represented by C2-5alkyl; R2 is represented by hydrogen, methyl or ethyl; R3 is represented by hydrogen; R4 is represented by C1-4alkyl; R5 is represented by a hydroxy group, 2,3-di-hydroxypropoxygroup or -OCH2-CH(OH)-CH2-NHCOR52; R52 is represented by hydroxymethyl, and R6 is represented by C1-4alkyl; and to its salt. The invention also refers to the pharmaceutical composition that is agonistic in relation to S1P1/EDG1 receptor on the basis of the mentioned compounds.

EFFECT: new compounds and a composition based on them that may find their application in medicine as immunomodulating agents.

17 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to new compounds of formula I-9 where q is represented by 1; R11 is represented by C3-8-alkyl; C3-8-cycloalkyl or C3-8-cycloalkyl-C1-3-alkyl; A is represented by phenyl substituted by one or more substituting groups independently chosen from R12; and R12 is represented by -(CH2)-NR13R14; R13 is represented by C1-6-alkylcarbanil; and R14 is represented by hydrogen; and to the pharmaceutically acceptable salts of such compounds and to the pharmaceutical compositions based on such compounds. It has been revealed that the compounds of formula I-9 are histamine NZ-receptor antagonists and thus that they can be used in treatment of diseases connected with expression of such receptors.

EFFECT: compounds of formula I-9 can be used in treatment of diseases connected with expression of histamine NZ-receptors.

6 cl, 216 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): where R1 and R2 represent hydrogen and a group which is hydrolysed in a physiological environment, optionally substituted lower alkanoyl or aroyl; X represents a methylene group; Y represents oxygen atom; n represents the number 0, 1, 2 or 3 and m represents the number 0 or 1; R3 represents a group of pyridine N-oxide according to formula A, B or C which is attached as shown by an unmarked linking: where R4, R5, R6 and R7 independently represent aryl, heterocycle, hydrogen, C1-C6-alkyl, C1-C6-alkylthio, C6-C12-aryloxy or C6-C12-arylthio group, C1-C6-alkylsulphonyl or C6-C12-arylsulphonyl, halogen, C1-C6-haloalkyl, trifluoromethyl, or heteroaryl group; or where two or more residues R4, R5, R6 and R7 taken together represent an aromatic ring, and where P represents a central part, preferentially chosen from regioisomers 1,3,4-oxadiazol-2,5-diyl, 1,2,4-oxadiazol-3,5-diyl, 4-methyl-4H-1,2,4-triazol-3,5-diyl, 1,3,5-triazine-2,4-diyl, 1,2,4-triazine-3,5-diyl, 2H-tetrazol-2,5-diyl, 1,2,3-thiadiazol-4,5-diyl, 1-alkyl-3-(alkoxycarbonyl)-1R-pyrrol-2,5-diyl, where alkyl is presented by methyl, thiazol-2,4-diyl, 1H-pyrazol-1,5-diyl, pyrimidine-2,4-diyl, oxazol-2,4-diyl, carbonyl, 1H-imidazol-1,5-diyl, isoxazol-3,5-diyl, furan-2,4-diyl, benzole-1,3-diyl and (Z)-1-cyanoethene-1,2-diyl, and where the regioisomers of the central part include both regioisomers produced by exchanging the nitrocatechol fragment and the -(X)n-(Y)m-R3 fragment. Also, the invention refers to a method for making a compound of formula I, as well as to a method for treating an individual suffering central and peripheral nervous system disorders, to a pharmaceutical composition based on the compounds of formula I, and also to their application for preparing the drug and as COMT inhibitor.

EFFECT: there are produced and described new compounds which show a potentially effective pharmaceutical properties in treating a number of central and peripheral nervous system disorders.

25 cl, 64 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I) where A denotes *-CO-CN=CH-, *-CO-CH2CH2-, or where the sign * indicates the thiophene bonding site in formula (I), R1 denotes hydrogen or methyl, R2 denotes n-propyl or isobutyl, R3 denotes hydrogen, methyl, ethyl, n-propyl, isopropyl or isobutyl, R4 denotes hydrogen or methoxy, R5 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy or hydrogen, R6 denotes -(CH2)k-(CHR65)p-CHR66-CONR61R62 hydroxy, hydroxy(C2-C4)alkoxy, di(hydroxy(C1-C4)alkyl)(C1-C4)alkoxy, 2,3-dihydroxypropoxy, -OCH2-(CH2)m-NHCOR64, -OCH2-CH(OH)-CH2-NR61R62, -OCH2- CH(OH)-CH2-NHCOR64 or -OCH2-CH(OH)-CH2-NHSO2R63, R61 denotes hydrogen, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylethyl, carboxymethyl or C1-C4alkylcarboxymethyl, R62 denotes hydrogen, R63 denotes methyl or ethyl, R64 denotes hydroxymethyl, methyl aminomethyl or 2-methyl aminoethyl, R65 denotes hydrogen, R66 denotes hydrogen, m equals 1 or 2, k equals 0, p equals 1, R67 denotes hydrogen, C1-C4alkyl or halogen, and to a salt thereof. The invention also relates to a pharmaceutical composition for preventing or treating diseases or disorders associated with an activated immune system based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as immunodepressants.

31 cl, 2 tbl, 114 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing benzo[b]thiophenes of the formula (I):

wherein X represents sulfur atom (S); R1 represents CN or COOA; each among R2 and R3 represents hydrogen atom; A represents (C1-C6)-alkyl. Method involves the dehydrogenation reaction of tetrahydrobenzothiophene of the formula (II):

wherein R1-R3 and X have values given above; Ac represents (C1-C6)-acyl in the presence of a catalyst taken in the catalytic amount based on precious metal and hydrogen acceptor followed by deacylation reaction of acylated amino-group by amine effect. Compounds of the formula (I) are intermediate substances in producing dyes, agents for plants protection and in manufacture of drugs.

EFFECT: improved preparing method.

7 cl, 3 ex

The invention relates to derivatives of benzo[b]thiophene acid of the formula I, the method of production thereof, which are useful as starting materials to obtain drugs, and to a method for producing derivatives of 5-hydroxybenzo[b] thiophene-3-carboxylic acid of formula VI, which are specific antagonists PGD2using the above derivatives of the formula I

The invention relates to a method for producing derivatives benzothiophenes formula I, including the interaction of amerosport formula (II) or its salt with the compound of the formula (III) or its reactive derivative, the oxidation of the resulting product in the presence of 2,2,6,6-tetramethylpiperidine-1-oxide and then liaising with ridom in the conditions of a Wittig reaction with subsequent optional unprotect

The invention relates to Amida aminodiphenylamine acid I in which R1, R2each independently of one another denotes N, And, moreover, one of the residues R1or R2in all cases has a value other than H; R1and R2together represent alkylene with 3-5 C-atoms, R3and R4each independently of one another denotes N or C1-C4-alkoxy; R3and R4together denote also-O-CH2-O - or-O-CH2-CH2-O-; And denotes alkyl with 1-6 C-atoms, R5means-X-Y, X represents CO, Y represents a phenyl or cyclohexyl, unsubstituted monosubstituted COOH or cooa, n denotes 1, 2 or 3, as well as their physiologically acceptable salts

The invention relates to benzodioxepine derivative, intermediate compounds for them, containing them, pharmaceutical compositions containing them antagonists PGD2(prostaglandin D2and containing medicines for the treatment of nasal obstruction

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where X denotes a 5-member heterocylic group bonded through a carbon atom, selected from thiophenyl, furanyl, pyrazolyl and pyrrolyl, which can be substituted with 1-3 Ra groups; T denotes O, S; B is as indicated in the claim; Z1 denotes an unsubstituted cyclopropyl; Z2 denotes a hydrogen atom, C1-C8alkyl; or C1-C8alkoxycarbonyl; Z3 independently denotes a hydrogen atom. The invention also relates to a fungicidal composition containing a compound of formula (I) as an active ingredient, and a plant pathogenic fungus control method in agricultural plants.

EFFECT: obtaining compounds of formula (I), having fungicidal activity.

9 cl, 3 dwg, 255 ex

FIELD: chemistry.

SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.

EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.

11 cl, 38 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae (1) and (2), where R1 is H or alkyl with 1-6 carbon atoms, R2 is H, alkyl with 1-6 carbon atoms or R1 and R2 together with a nitrogen atom form a saturated or unsaturated 5-, 6- or 7-member ring which can also include one or two heteroatoms independently selected from N, O or S. Said 5-, 6- or 7-member ring is possibly substituted with one or two OH groups or halogen groups, and said 5-, 6- or 7-member ring is possibly condensed with an aromatic or non-aromatic 5- or 6-member ring; R3 is independently selected from H, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, phenyl or phenyl-alkyl, where the alkyl group has 1-4 carbon atoms, phenyl(hydroxy)alkyl, where the alkyl group has 1-4 carbon atoms, wherein said phenyl groups are possibly substituted with 1-3 groups independently selected from a group comprising halogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, or R3 is CO-R7 or CO-O-R7, where R7 is H, alkyl with 1-20 carbon atoms, optionally substituted with a NH2 group or NH-CO alkyl group, where the alkyl group has 1-6 carbon atoms, phenyl or phenyl-alkyl, where the alkyl group has 1-4 carbon atoms, wherein said phenyl groups are possibly substituted with 1-3 groups independently selected from a group comprising halogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, is H, alkyl with 1-6 carbon atoms or CO-R8, where R8 is alkyl with 1-6 carbon atoms; wavy lines denote bonds with carbon atoms, having an R or S configuration; dotted lines denote a bond or absence of a bond provided that the ring containing dotted lines is aromatic; m, n and q are whole numbers independently selected from 0, 1, 2 or 3, provided that the sum of m, n and q equals 2 or 3; s equals 0 or 1; W, X and Y independently denote CH, CR5, CR6 or a heteroatom independently selected from N, O and S, and R5 and R6 are independently selected from H, halogen, alkyl with 1-6 carbon atoms, halogen-substituted alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms and thioxy with 1-3 carbon atoms, phenyl, or R5 and R6 together with atoms to which they are bonded form a carbocyclic ring which has 6 atoms in the ring, or a heterocyclic ring which has 5 or 6 atoms in the ring and 1-3 heteroatoms independently selected from N, O and S. Said carbocyclic or heterocyclic ring, formed jointly by R5 and R6, is possibly substituted with 1-6 R9 groups, where R9 is a halogen.

EFFECT: higher pain-killing and immune-stimulating action.

65 cl, 1 tbl, 256 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (II-A) or pharmaceutically acceptable salt thereof: [in which symbols denote the following: R10-R12: are identical or different and each denotes halogen, lower alkyl, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, R13: R0, halogen, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, ring B: benzene ring or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from O, S and N, R14: R0, halogen or -OR0, R0: are identical or different and each denotes H or lower alkyl, Y1: a single bond, lower alkylene, lower alkenylene or O-lower alkylene-, and Z1: -CO2R0 or -C0-NH-SO2-lower alkyl]. The invention also relates to a pharmaceutical composition based on the said compound, having antagonistic effect on the EP1 receptor.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in a medicinal agent for treating lower urinary tract symptoms.

6 cl, 56 tbl, 231 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to acyloxyalkylcarbamate prodrugs (±)4-amino-3-(4-chlorophenyl)butanoic acid, to based pharmaceutical compositions and to their application, for treating spasticity or a spasticity symptom, gastroesophageal reflux disease (GERD), drug addiction, alcohol addiction or alcohol abuse, or cough, or vomiting. Acyloxyalkylcarbamate prodrugs represent a compound of formula (V) or its pharmaceutically acceptable salt where R1 is selected from C1-C6alkyl substituted by C1-C6alkyl, C3-C6cycloalkyl, phenyl, phenyl C1-C6alkyl substituted by phenyl C1-C6alkyl, phenylC2-C6alkenyl, C5-C6heteroaryl containing 1 nitrogen, oxygen or sulphur atom as a heteroatom; R2 and R3 are independently selected from hydrogen, C1-C6alkyl and C3-C6cycloalkyl; R4 is selected from: hydrogen, phenyl, phenyl C1-C6alkyl and C1-C6alkyl and where "substituted" means a group wherein one or two hydrogen atoms are substitute by a substitute which represent C1-C6alkoxy. Also, the invention refers to an intermediate compound of formula (VII) and its pharmaceutically acceptable salt where X represents: fluorine, chlorine, bromine or iodine; R2 and R3 are independently selected from hydrogen and C1-C6alkyl; R4 is selected from: hydrogen, C1-C6alkyl, phenyl and phenyl C1-C6alkyl.

EFFECT: preparation of the acyloxyalkylcarbamate prodrugs (±)4-amino-3-(4-chlorophenyl)butanoic acid which are applicable for the oral introduction and oral introduction with using prolonged release dosage forms.

23 cl, 3 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention describes N-cycloalkylbenzylamide derivatives of formula

, where A denotes a saturated 5-member heterocyclic group, Z1 denotes a substituted C3-C7-cycloalkyl; Z2 and Z3, which can be identical or different from each other, denote a hydrogen atom; C1-C8-alkyl; cyano; C1-C8-alkoxycarbonyl; a method of producing said compounds, use thereof as fungicidal active substances, particularly in form of fungicidal compositions, and method of controlling phytopathogenic fungi, mainly in plants, using said compounds or compositions.

EFFECT: higher activity, low amount of active substance while maintaining efficiency at least equivalent to that of existing compounds.

11 cl, 5 ex

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