US 2006/0217432 A1Published application

3,6-Disubstituted azabicyclo [3.1.0] hexane derivatives as muscarinic receptor antagonists

AssigneeRanbaxy Laboratories Limited

InventorsAnita Mehta, Arundutt Silamkoti, Bruhaspathy Miriyala, Sudershan Arora, Boju Srinivasulu, Bireshwar Mukherjee, Jang Gupta

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Abstract

The invention relates to derivatives of 3,6-disubstituted azabicyclo[3.1.0]hexanes of structure (I). The compounds of this invention can function as muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.

Claims38

Dependent claims

A compound having the structure of Formula I

and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantioners, diastereomers, N-oxides, polymorphs, prodrugs, or metabolites, wherein
Ar represents an aryl or a heteroaryl ring having 1-2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms, the aryl or heteroaryl rings may be unsubstituted or substituted by one to three substituents independently selected from straight or branched lower alkyl (C1-C4), trifluoromethyl, methylenedioxy, cyano, hydroxy, halogen (e.g. F, Cl, Br, I), nitro, lower alkoxy (C1-C4), aryloxy, amino or lower alkylamino;
R1 represents C3-C9 cycloalkyl ring, a C3-C9 cyclo alkenyl ring, an aryl or a heteroaryl ring having 1 to 2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms, the aryl or a heteroaryl ring may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C1-C4), trifluoromethyl, cyano, hydroxy, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C1-C4), unsubstituted amino or lower alkyl (C1-C4) amino;
R2 represents a hydrogen, hydroxy, amino, alkoxy, alkenyloxy, alkynyloxy, carbamoyl or halogen (e.g. F, Cl, Br, I);
W represents (CH2)p, where p represents 0 to 1;
X represents an oxygen, sulphur, NR, or no atom, where R is H or lower alkyl (C1-C4);
Y represents (CHR5)q CO wherein R5 represents hydrogen or methyl;
or y represents (CH2)q wherein q represents 0 to 4;
m represents 0 to 2;
R3 represents hydrogen, lower alkyl or CO2C(CH3)3;
R4 represents hydrogen, C1-C15 saturated or unsaturated aliphatic hydrocarbon groups in which any 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on an aryl or heteroaryl ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl, trifluoromethyl, cyano, hydroxyl, carboxylic acid, nitro, lower alkoxycarbonyl, halogen, lower alkoxy, amino, lower alkylamino, loweralkyl carbonyl amino, loweralkyl thiocarbonyl amino or loweralkyl carbonyl amino sulphonyl and pharmaceutically acceptable salts thereof.

8 more elements

A compound selected from the group consisting of:

(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-hydroxy-2,2-diphenyl acetamide (Compound No. 1),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-hydroxy-2,2-di(4-fluoro phenyl)acetamide (Comound No. 2),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-(2-propenyloxy)-2,2-diphenyl acetamide (Compound No. 3),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-(2-propenyloxy)-2,2-di(4-fluorophenyl)acetamide (Compound No. 4),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-propyloxy-2,2-diphenyl acetamide (Compound No. 5),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-propyloxy-2,2-di(4-fluoro phenyl)acetamide (Compound No. 6),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-(2-propynyloxy)-2,2-diphenyl acetamide (Compound No. 7),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-hydroxy-2,2-di(2-furyl)acetamide (Compound No. 8),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-hydroxy-2,2-di(2-thienyl)acetamide (Compound No. 9),
(1α,5α,6α)-4-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)butyl-1-(2-hydroxy-2,2-diphenyl)acetate (Compound No. 10),
(1α,5α,6α)-3-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tertbutyloxycarbonyl)propyl-1-(2-hydroxy-2,2-diphenyl)acetate (Compound No. 11),
(1α,5α,6α)-3-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)propyl-1-(2-propyloxy-2,2-diphenyl)acetate (Compound No. 12),
(1α,5α,6α)-4-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)butyl-1-(2-propyloxy-2,2-diphenyl)acetate (Compound No. 13),
(1α,5α,6α)-4-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)butyl-1-(2-(2-propenyloxy)-2,2-diphenyl)acetate (Compound No. 14),
(1α,5α,6α)-4-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)butyl-1-(2-hydroxy-2,2-di(4-fluorophenyl))acetate (Compound No. 15),
(1α,5α,6α)-4-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-tert-butyloxy carbonyl)butyl-1-(2-propyloxy-2,2-di(4-fluorophenyl))acetate (Compound No. 16),
(1α,5α,6α)-1-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-acetamido-2-(2-propyloxy)-2,2-diphenyl acetate (Compound No. 17),
(1α,5α,6α)-1-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-acetamido-2-(2-propenyloxy)-2,2-diphenyl acetate (Compound No. 18),
(1α,5α,6α)-1-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-propionamido-2-(2-propenyloxy)-2,2-diphenyl acetate (Compound No. 19),
(1α,5α,6α)-1-(6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-propionamido-2-2-propyloxy)-2,2-diphenyl acetate (Compound No. 20),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl))-N-acetamido-2-hydroxy-2,2-di(4-fluorophenyl)acetate (Compound No. 21),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 22),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(3,5-difluorobenzyl))-2-cyclo hexyl-2-hydroxy-2-phenyl acetamide (Compound No. 23),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-bromobenzyl))-2-cyclo hexyl-2-hydroxy-2-phenyl acetamide (Compound No. 24),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2,6-difluorobenzyl))-2-cyclo hexyl-2-hydroxy-2-phenyl acetamide (Compound No. 25),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-phenylbenzyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 26),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-phenylethyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 27),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(2,3-dihydrobenzofuran-5-yl)ethyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 28),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(3,4-methylenedioxyphenyl)ethyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 29),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(1-(2,3-dihydrobenzofuran-5-yl)acetyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 30),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(benzofuran-5-yl)ethyl))-2-cyclo hexyl-2-hydroxy-2-phenyl acetamide (Compound No. 31),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-methyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 32),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-ethyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 33),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(1-propyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 34),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-propargyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 35),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-propenyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 36),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-propyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 37),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-cyclopropyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 38),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(1-butyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 39),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(3-methyl-2-butenyl))-2-cyclo hexyl-2-hydroxy-2-phenyl acetamide (Compound No. 40),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 41),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(3,4-methylenedioxybenzyl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 42),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(6,6-dimethyl-2,4-heptadiynyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 43),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzoyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 44),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-formyl-fur-5-yl))-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 45),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(aniline)thiourea)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 46),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(methyl,4-amino-1-phenyl acetate)urea)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 47),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-amino-1-phenyl acetic acid)urea)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 48),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methylphenyl-1-sulphonamide)urea)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 49),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(4-methylphenyl)acetamide (Compound No. 50),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(4-methoxyphenyl)acetamide (Compound No. 51),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(4-phenoxyphenyl)acetamide (Compound No. 52),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(4-fluorophenyl)acetamide (Compound No. 53).
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(3,4-methylenedioxyphenyl)acetamide (Compound No. 54),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-hydroxy-2-(4-tertbutylphenyl)acetamide (Compound No. 55).
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclohexyl-2-hydroxy-2-(4-methylphenyl)acetamide (Compound No. 56),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclo hexyl-2-hydroxy-2-(4-methoxyphenyl)acetamide (Compound No. 57),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclohexyl-2-hydroxy-2-(4-fluorophenyl)acetamide (Compound No. 58),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-methoxy-2-phenyl acetamide (Compound No. 59),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-ethyl)-2-cyclohexyl-2-methoxy-2-phenyl acetamide (Compound No. 60),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclohexyl-2-(2-propenyloxy)-2-phenyl acetamide (Compound No. 61),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclohexyl-2-methoxy-2-phenyl acetamide (Compound No. 62),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2,4-difluorobenzyl))-2-cyclohexyl-2-methoxy-2-phenyl acetamide (Compound No. 63),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 64),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 65),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(3,4-methylenedioxyphenyl)ethyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 66),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-phenylethyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 67),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(2,3-dihydrobenzofuran-5-yl)ethyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 68),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-methyl-pyrid-6-yl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 69),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(1-(2,3-dihydrobenzofuran-5-yl)acetyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 70),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(2-(benzofuran-5-yl)ethyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 71),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-2-cycloheptyl-2-hydroxy-2-phenyl acetamide (Compound No. 72),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cycloheptyl-2-hydroxy-2-phenyl acetamide (Compound No. 73),
2-Amino-((1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)propionamido)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 74),
2-Amino-((1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)acetamido)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide. (Compound No. 75),
3-Amino-((1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)propionamido)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 76),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)-3-cyclohexyl-3-hydroxy-3-phenyl propionamide (Compound No. 77),
2-Amino-((1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)acetamido)-3-cyclohexyl-3-hydroxy-3-phenyl propionamide (Compound No. 78),
2-Amino-((1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-benzyl)propionamido)-2-cyclohexyl-3-hydroxy-3-phenyl propionamide (Compound No. 79),
(1α,5α,6α)-2-[6-N-(3-benzyl-3-azabicyclo[3.1.0]hexyl)-N-propionamido-2-cyclohexyl-2-hydroxy-2-phenyl acetate (Compound No. 80),
(2R)(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 81),
(2R)(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(3,4-methylenedioxy phenyl)ethyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 82),
(2R)-(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide succinate salt. (Compound No. 83),
(2R)-(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl-3-(4-methyl-3-pentenyl))-2-cyclopentyl-2-hydroxy-2-phenyl acetamide L-(+)-tartrate salt. (Compound No. 84),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclohexyl-2-hydroxy-2-phenyl acetamide (Compound No. 85),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclohexyl-2-hydroxy-2-(4-fluorophenyl)acetamide (Compound No. 86),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclohexyl-2-hydroxy-2-(4-methoxyphenyl)acetamide (Compound No. 87),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclohexyl-2-hydroxy-2-(4-methylphenyl)acetamide (Compound No. 88),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclopentyl-2-hydroxy-2-phenyl acetamide (Compound No. 89),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cycloheptyl-2-hydroxy-2-phenyl acetamide (Compound No. 90),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclobutyl-2-hydroxy-2-phenyl acetamide (Compound No. 91),
(1α,5α,6α)-6-N-(3-azabicyclo[3.1.0]hexyl)-2-cyclopropyl-2-hydroxy-2-phenyl acetamide (Compound No. 92),
(1α,5α,6α)-1-[6N-(3-azabicyclo[3.1.0]hexyl)]-N-acetamido-2-hydroxy-2-cyclohexyl-2-phenylacetate (Compound No. 93),
(1α,5α,6α)-1-[6N-(3-azabicyclo[3.1.0]hexyl)]-N-propionamido-2-hydroxy-2-cyclohexyl-2-phenylacetate (Compound No. 94),
(1α,5α,6α)-4-[6N-(3-azabicyclo[3.1.0]hexyl)]-N-(tert-butyloxy carbonyl)butyl-1-[2-hydroxy-2,2-bis(4-fluorophenyl)]acetate (Compound No. 95),
(1α,5α,6α)-4-[6N-(3-azabicyclo[3.1.0]hexyl)]-N-(tert-butyloxy carbonyl)butyl-1-[2-propyloxy-2,2-bis(4-fluorophenyl)]acetate (Compound No. 96),
(1α,5α,6α)-6N-(3-azabicyclo[3.1.0]hexyl)-2,2-diphenyl acetamide (Compound No. 97),
(1α,5α,6α)-6N-(3-azabicyclo[3.1.0]hexyl)-2-cyclohexyl-2-methoxy-2-phenylacetamide (Compound No. 98).

95 more elements

A method for treatment or prophylaxis of an animal or a human suffering from a disease or disorder of the respiratory, urinary and gastrointestinal systems wherein the disease or disorder is mediated through muscarinic receptors, comprising administering to said animal or human, a therapeutically effective amount of a compound having the structure of Formula I

and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantioners, diastereomers, N-oxides, polymorphs, prodrugs, or metabolites, wherein
Ar represents an aryl or a heteroaryl ring having 1-2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms, the aryl or heteroaryl rings may be unsubstituted or substituted by one to three substituents independently selected from straight or branched lower alkyl (C1-C4), trifluoromethyl, methylenedioxy, cyano, hydroxy, halogen (e.g. F, Cl, Br, I), nitro, lower alkoxy (C1-C4), aryloxy, amino or lower alkylamino;
R1 represents C3-C9 cycloalkyl ring, a C3-C9 cyclo alkenyl ring, an aryl or a heteroaryl ring having 1 to 2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms;
the aryl or a heteroaryl ring may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C1-C4), trifluoromethyl, cyano, hydroxy, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C1-C4), unsubstituted amino or lower alkyl (C1-C4) amino;
R2 represents a hydrogen, hydroxy, amino, alkoxy, alkenyloxy, alkynyloxy, carbamoyl or halogen (e.g. F, Cl, Br, I);
W represents (CH2)p, where p represents 0 to 1;
X represents an oxygen, sulphur, NR, or no atom, where R is H or lower alkyl (C1-C4);
Y represents (CHR5)q CO wherein R5 represents hydrogen or methyl;
or
Y represents (CH2)q wherein q represents 0 to 4;
m represents 0 to 2;
R3 represents hydrogen, lower alkyl or CO2C(CH3)3;
R4 represents hydrogen, C1-C15 saturated or unsaturated aliphatic hydrocarbon groups in which any 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on an aryl or heteroaryl ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl, trifluoromethyl, cyano, hydroxyl, carboxylic acid, nitro, lower alkoxycarbonyl, halogen, lower alkoxy, amino, lower alkylamino, loweralkyl carbonyl amino, loweralkyl thiocarbonyl amino or loweralkyl carbonyl amino sulphonyl.

10 more elements

A process of preparing a compound of Formula I,

and its pharmaceutical acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, prodrugs or metabolites wherein
Ar represents an aryl or a heteroaryl ring having 1-2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms, the aryl or heteroaryl rings may be unsubstituted or substituted by one to three substituents independently selected from straight or branched lower alkyl (C1-C4), trifluoromethyl, methylenedioxy, cyano, hydroxy, halogen (e.g. F, Cl, Br, I), nitro, lower alkoxy (C1-C4), aryloxy, amino or lower alkylamino;
R1 represents C3-C9 cycloalkyl ring, a C3-C9 cyclo alkenyl ring, an aryl or a heteroaryl ring having 1 to 2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms;
the aryl or a heteroaryl ring may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C1-C4), trifluoromethyl, cyano, hydroxy, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C1-C4), unsubstituted amino or lower alkyl (C1-C4) amino;
R2 represents a hydrogen, hydroxy, amino, alkoxy, alkenyloxy, alkynyloxy, carbamoyl or halogen (e.g. F, Cl, Br, I);
W represents (CH2)p, where p represents 0 to 1;
X represents an oxygen, sulphur, NR, or no atom, where R is H or lower alkyl (C1-C4);
Y represents (CHR5)q CO wherein R5 represents hydrogen or methyl;
or
Y represents (CH2)q wherein q represents 0 to 4;
m represents 0 to 2;
R3 represents hydrogen, lower alkyl or CO2C(CH3)3;
R4 represents hydrogen.
(a) condensing a compound of Formula VII with a compound of Formula VIII
wherein Ar, R1, R2, R3, W, X, Y and m have the same meanings as defined earlier, P is any group which can be used to protect an amino group, in the presence of a condensing agent to give a protected compound of Formula IX, and
(b) deprotecting the compound of Formula IX in the presence of a deprotecting agent to give a compound of Formula X,
wherein Ar, R1, R2, R3, W, X, Y, m and P are the same as defined earlier.

14 more elements

A process of preparing a compound of Formula I,

and its pharmaceutical acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, prodrugs or metabolites wherein
Ar represents an aryl or a heteroaryl ring having 1-2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms, the aryl or heteroaryl rings may be unsubstituted or substituted by one to three substituents independently selected from straight or branched lower alkyl (C1-C4), trifluoromethyl, methylenedioxy, cyano, hydroxy, halogen (e.g. F, Cl, Br, I), nitro, lower alkoxy (C1-C4), aryloxy, amino or lower alkylamino;
R1 represents C3-C9 cycloalkyl ring, a C3-C9 cyclo alkenyl ring, an aryl or a heteroaryl ring having 1 to 2 hetero atoms selected from the group consisting of oxygen, sulphur and nitrogen atoms;
the aryl or a heteroaryl ring may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C1-C4), trifluoromethyl, cyano, hydroxy, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C1-C4), unsubstituted amino or lower alkyl (C1-C4) amino;
R2 represents a hydrogen, hydroxy, amino, alkoxy, alkenyloxy, alkynyloxy, carbamoyl or halogen (e.g. F, Cl, Br, I);
W represents (CH2)p, where p represents 0 to 1;
X represents an oxygen, sulphur, NR, or no atom, where R is H or lower alkyl (C1-C4);
Y represents (CHR5)q CO wherein R5 represents hydrogen, or methyl;
or
Y represents (CH2)q wherein q represents 0 to 4;
m represents 0 to 2;
R3 represents hydrogen, lower alkyl or CO2C(CH3)3;
R4 represents C1-C15 saturated or unsaturated aliphatic hydrocarbon groups in which any 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on an aryl or heteroaryl ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl, trifluoromethyl, cyano, hydroxyl, carboxylic acid, nitro, lower alkoxycarbonyl, halogen, lower alkoxy, amino, lower alkylamino, loweralkyl carbonyl amino, loweralkyl thiocarbonyl amino or loweralkyl carbonyl amino sulphonyl, comprising
(a) condensing a compound of Formula VII with a compound of Formula VIII
wherein Ar, R1, R2, R3, W, X, Y and m have the same meanings as defined earlier, P is any group which can be used to protect an amino group, in the presence of a condensing agent to give a protected compound of Formula IX,
(b) deprotecting the compound of Formula IX in the presence of a deprotecting agent to give a compound of Formula X,
wherein Ar, R1, R2, R3, W, X, Y, m and P are the same as defined earlier, and
(c) N-alkylating or benzylating the compound of Formula X with a suitable alkylating or benzylating agent L-R4 wherein L is a leaving group and R4 is as defined earlier, to give a compound of Formula I.

15 more elements

Dependencies are inferred from the claim text.