FIELD OF THE INVENTION
This invention generally relates to derivatives of 3,6-disubstituted azabicyclo hexanes.
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 of treating the diseases mediated through muscarinic receptors.
BACKGROUND OF THE INVENTION
Muscarinic receptors as members of the G Protein Coupled Receptors (GPCRs) are composed of a family of 5 receptor sub-types (Mi, Ma, MS, M4 and Ms) and are activated by the neurotransmitter acetylcholine. These receptors are widely distributed on multiple organs and tissues and are critical to the maintenance of central and peripheral cholinergic neurotransmission. The regional distribution of these receptor sub-types in the brain and other organs has been documented. For example, the MI subtype is located primarily in neuronal tissues such as cereberal cortex and autonomic ganglia, the Ma subtype is present mainly in the heart where it mediates cholinergically induced bradycardia, and the Ma subtype is located predominantly on smooth muscle and salivary glands (Nature. 1986; 323: 411; Science, 1987; 237: 527). A review in Current Opinions in Chemical Biology. 1999; 3: 426, as well as in Trends in Pharmacological Sciences. 2001; 22: 409 by Eglen et. al., describe the biological potentials of modulating muscarinic receptor subtypes by ligands in different disease conditions like Alzheimer's disease, pain, urinary disease condition, chronic obstructive pulmonary disease etc.
A review in J. Med. Chem.. 2000; 43: 4333 by Christian C. Felder et. al. describes therapeutic opportunities for muscarinic receptors in the central nervous system and elaborates on muscarinic receptor structure and function, pharmacology and their therapeutic uses.
The pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists are presented in a review in Molecules. 2001, 6: 142.
N.J.M. Birdsall et. al. in Trends in Pharmacological Sciences. 2001; 22: 215 have also summarized the recent developments on the role of different muscarinic receptor subtypes using different muscarinic receptors of knock out mice.

Muscarinic agonists such as muscarine and pilocarpine and antagonists such as atropine have been known for over a century, but little progress has been made in the discovery of receptor subtype-selective compounds making it difficult to assign specific functions to the individual receptors. Although classical muscarinic antagonists such as atropine are potent bronchodilators, their clinical utility is limited due to high incidence of both peripheral and central adverse effects such as tachycardia, blurred vision, dryness of mouth, constipation, dementia, etc. Subsequent development of the quarterly derivatives of atropine such as ipratropium bromide are better tolerated than parenterally administered options but most of them are not ideal anti-cholinergic bronchodilators due to lack of selectivity for muscarinic receptor sub-types. The existing compounds offer limited therapeutic benefit due to their lack of selectivity resulting in dose limiting side effects such as thirst, nausea, mydriasis and those associated with the heart such as tachycardia mediated by the M2 receptor.
Annual review of Pharmacological Toxicol.. 2001; 41: 691, describes the pharmacology of the lower urinary tract infections. Although anti muscarinic agents such as oxybutynin and tolterodine that act non-selectively on muscarinic receptors have been used for many years to treat bladder hyperactivity, the clinical effectiveness of these agents has been limited due to the side effects such as dry mouth, blurred vision and constipation. Tolterodine is considered to be generally better tolerated than oxybutynin. (W.D. Steers et. al. in Curr. Qpin. Invest. Drugs. 2: 268, C.R. Chappie et. al. in Urology. 55: 33), Steers WD, Barrot DM, Wein AJ, 1996, Voiding dysfunction: diagnosis classification and management. In "Adult and Pediatric Urology," ed. JY Gillenwatter, JT Grayhack, SS Howards, JW Duckett, pp 1220-1325, St. Louis, MO; Mosby. 3rd edition.)
Despite these advances, there remains a need for development of new highly selective muscarinic antagonists, which can interact with distinct subtypes, thus avoiding the occurrence of adverse effects.
Compounds having antagonistic activity against muscarinic receptors have been described in Japanese patent application Laid Open Number 92921/1994 and 135958/1994; WO 93/16048; U.S. Patent No. 3,176,019; GB 940,540; EP 0325 571; WO 98/29402; EP 0801067; EP 0388054; WO 9109013; U.S. Patent No. 5,281,601. U.S. Patent Nos. 6,174,900, 6,130,232 and 5,948,792; WO 97/45414 are related to 1,4-disubstituted piperidine derivatives; WO 98/05641 describes fluorinated, 1,4-disubstitued piperidine derivatives; WO 93/16018 and WO96/33973 are other close art references.

A report in J. Med. Chem.. 2002; 44:984, describes cyclohexylmethyl piperidinyl triphenylpropioamide derivatives as selective MS antagonist discriminating against the other receptor subtypes.
SUMMARY OF THE INVENTION
The present invention provides 3,6-disubstituted azabicyclo hexanes, which function as muscarinic receptor antagonists and are useful as safe treatment of various diseases of the respiratory, urinary and gastrointestinal systems, and methods for the syntheses of the compounds. The present invention includes 3,6-disubstituted azabicyclo [3.1.0], [3.1.1] and [3.1.2] hexanes.
The invention also provides pharmaceutical compositions containing the compounds, and which may also contain acceptable carriers, excipients or diluents which are useful for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems.
The present invention also includes within its scope prodrugs of the compounds. In general, such prodrugs are functionalized derivatives of these compounds, which readily get converted in vivo into the defined compounds. Conventional procedures for the selection and preparation of suitable prodrugs are known to the artisan of ordinary skill in the art.
The invention also includes the enantiomers, diastereomers, N-oxides, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters and metabolites of these compounds having the same type of activity.
The invention further includes pharmaceutical compositions comprising the compounds of the present invention, their enantiomers, diastereomers, prodrugs, N-oxides, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, or metabolites in combination with a pharmaceutically acceptable carrier and optionally included excipients.
Other advantages of the invention will be set forth in the description which follows, and in part will be apparent from the description or may be learnt by the practice of the invention. The objects and the advantages of the invention may be realized and obtained by means of the mechanisms and combinations pointed out in the appended claims.
In accordance with one aspect of the present invention, there is provided a compound having the structure of Formula I:
(Formula Removed)

and its pharmaceutically 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 lower alkyl (C|-C4), trifluoromethyl, cyano, hydroxy, nitro, halogen (e.g. F, Cl, Br or I), lower alkoxy (Ci-C4), amino or lower alkylamino (Ci-C4);
RI represents hydrogen, hydroxy, hydroxymethyl, loweralkyl (Ci-C4), amino, alkoxy, cycloalkyl (Cs-C?), carbamoyl, halogen (e.g. F, Cl, Br, I) or aryl;
R2 represents alkyl, Cs-C? cycloalkyl ring, Cs-C? cycloalkenyl 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 hetero aryl ring may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (Ci-C4), trifluoromethyl, cyano, hydroxy, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (Ci-C4), unsubstituted amino or lower alkyl (Ci-C4) amino;
W represents (CH2)P, where p represents 0 to 1;
X represents an oxygen, sulphur, NR or no atom wherein R represents hydrogen or Ci-6 alkyl;
Y represents CHRsCO wherein Rs represents hydrogen or methyl or (CH2)q wherein q represents 0 to 4; m represents 0 to 2;
Ra represents hydrogen, lower alkyl (Q-C4) or CC^C (CH^;
RA represents Ci-Cis saturated or unsaturated aliphatic hydrocarbon (straight chain or branched) in which any 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen (e.g. F, Cl, Br, I), carboxylic acid, carboxylic acid ester, aryl, aryloxy, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur with an option that any 1 to 5 hydrogen atoms on an aryl or heteroaryl ring in said aryl, aryloxy, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkenyl group may be substituted with lower alkyl, trifluoromethyl, halogen (e.g. F, Cl, Br, I), cyano, nitro, hydroxy, lower (Ci-C4) alkoxy, amino, lower (Ci-C4) alkylamino, sulphonylamino, amide, carboxylic acid, carboxylic acid ester or benzyl ester.
In accordance with a second aspect of the present invention, there is provided a compound having the structure of Formula II and its pharmaceutically acceptable salts,

pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides,
polymorphs, prodrugs, metabolites, wherein Ar, RI, Rj, RS, Rt, W, X and Y are as defined for
Formula(Formula Removed)
I.
H
Formula II In accordance with a third aspect of the present invention, there is provided a
compound having the stucture of Formula III and its pharmaceutically acceptable salts,
pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides,
polymorphs, prodrugs, metabolites, wherein Ar, RI, Rj, Rs and Rt are as defined for
Formula
(Formula Removed)


F

H
Formula III In accordance with a fourth aspect of the present invention, there is provided a
compound having the structure of Formula IV and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, prodrugs, metabolites, wherein Ar, RI, Rs and RI are as defined for Formula I and r is 1 to 4.
(Formula Removed)
In accordance with a fifth aspect of the present invention, there is provided a
compound having the stucture of Formula V and its pharmaceutically acceptable salts,
pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides,
polymorphs, prodrugs, metabolites, wherein Ar, RI, Ra and R} are as defined for Formula I
and s is 1 to 3. u

(Formula Removed)

In accordance with a sixth aspect of the present invention, there is provided a compound having the stucture of Formula VI and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, prodrugs, metabolites, wherein Formula VI wherein Rs, R4 and s are the same as

defined for Formula V. H(Formula Removed)

-MS
Formula VI In accordance with a seventh aspect of the present invention, there is provided 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 a patient in need thereof, an effective amount of compounds as described above.
In accordance with an eighth aspect of the present invention, there is provided a method for treatment or prophylaxis of an animal or a human suffering from a disease or disorder of the respiratory systems such as bronchial asthma, chronic obstructive pulmonary disorders (COPD), pulmonary fibrosis, etc., urinary system which induce such urinary disorders as urinary incontinence, lower urinary tract systems (LUTS), etc., and gastrointestinal system such as irritable bowel syndrome, obesity, diabetes and gastrointestinal hyperkinesis with compounds as described above, wherein the disease or disorder is associated with muscarinic receptors, comprising administering to a patient in need thereof, an effective amount of compounds as described above.
In accordance with a ninth aspect of the present invention, there is provided a process for preparing the compounds as described above.
The compounds of the present invention exhibit significant potency in terms of their activity, which was determined by in vitro receptor binding and functional assays and in vitro experiments using anaesthetized rabbit. Compounds were tested in vitro and in vitro. Some compounds were found to function as potent muscarinic receptor antagonists with high affinity towards Ms receptors. Therefore, the present invention provides pharmaceutical compositions for treatment of diseases or disorders associated with muscarinic receptors. Compounds and compositions described herein can be administered orally or parenterally.

DETAILED DESCRIPTION OF THE INVENTION
The compounds described herein may be prepared by the reaction sequence as shown in Scheme-I.
(Formula Removed)
The preparation comprises condensing a compound of Formula VII with the compound of Formula VIII, wherein Ar, RI, R2, W, X, Y, m, Ra are the same as defined earlier and P is any group which can be used to protect an amino group and is selected from benzyl and t-butyloxy carbonyl groups, in the presence of a condensing agent to give a

protected compound of Formula IX wherein RI, R2, Ra, W, X, Y, P and m are as defined earlier, which on deprotection through reaction with a deprotecting agent in an organic solvent gives an unprotected compound of Formula X wherein RI, R2, Rs, W, X, Y and m are the same as defined earlier, which is finally N-alkylated or benzylated with a suitable alkylating or benzylating agent L-R4 wherein L is any leaving group known in the art, to give a compound of Formula I.
The reaction of the compound of Formula VII with a compound of Formula VIII to give a compound of Formula IX can be carried out in the presence of a condensing agent, for example l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU).
The reaction of the compound of Formula VII with a compound of Formula VIII to give a compound of Formula IX can be carried out in a suitable solvent, for example N,N-dimethylformamide, dimethylsulfoxide, toluene and xylene at a temperature ranging from about0-140°C.
The deprotection of the compound of Formula IX to give a compound of Formula X can be carried out with a deprotecting agent, for example palladium on carbon, trifluoroacetic acid (TFA) and hydrochloric acid.
The deprotection of the compound of Formula IX to give a compound of Formula X can be carried out in a suitable organic solvent, for example methanol, ethanol, tetrahydrofuran and acetonitrile at temperatures ranging from about 10-50°C.
The N-alkylation or benzylation of the compound of Formula X to give a compound of Formula I can be carried out with a suitable alkylating or benzylating agent, L-R4 wherein L is any leaving group, known in the art, for example halogen, O-mestyl and O-tosyl group.
The N-alkylation or benzylation of the compound of Formula X to give a compound of Formula I can be carried out in a suitable organic solvent such as N,N-dimethylformamide dimethylsulfoxide, tetrahydrofuran and acetonitrile, at temperatures ranging from about 25 to about100°C.
In the above scheme, where specific bases, condensing agents, protecting groups, deprotecting agents, N-alkylating/benzylating agents, solvents, catalysts etc. are mentioned, it is to be understood that other bases, condensing agents, protecting groups, deprotecting agents, N-alkylating/benzylating agents, solvents, catalysts etc. known to those skilled in the art may be used. Similarly, the reaction temperature and duration may be adjusted according to the desired needs.

An illustrative list of particular compounds, which are capable of being produced by Scheme I, include:
1. (lα,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-(4-methoxy)phenylacetamide
2. (lα,5α,6α)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
3. (lα,5α,6α)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopenty 1-2-pheny lacetamide
4. (lα,5α,6α)N-[3-(5-nitro-2-furylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopenty 1-2-pheny lacetamide
5. (la,5a,6a)-N-[3-(4-methyl-pentyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
6. (lα,5α,6α)-N-[3-(2-(l,4-benzodioxan-6-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
7. (lα,5α,6α)-N-[3-(3,4,5-trimethoxyphenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
8. (lα,5α,6α)N-[3-[3-(3,4-methylenedioxyphenyl)propyl)]-3-azabicyclo[3.1.0]hex-6-
yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
9. (lα,5α,6α))-N-[3-(3,4,5-trimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
10. v(lα,5α,6α)-N-[3-(3,5-dimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopenty 1-2-pheny lacetamide
11. (lα,5α,6α)-N-[3-(3,4-dimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
12. v(lα,5α,6α)-N-[3-(3-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
13. (lα,5α,6α)-N-[3-(4-trifluoromethylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
14. (lα,5α,6α)-N-[3-(5-methyl-2-furylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
15. (lα,5α,6α)-N-[3-(2-(4-methylphenoxy)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
16. (lα,5α,6α)-N-[3-(3-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
17. (lα,5α,6α)-N-[3-(4-chlorophenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
18. (lα,5α,6α)-N-[3-(4-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
19. ((lα,5α,6α)-N-[3-(3-phenylpropyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide


20. (lα,5α,6α)-N-[3-(3-hydroxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
21. v(lα,5α,6α)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
22. (lα,5α,6α)-N-[3-(4-t-butylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
23. (lα,5α,6α)N-[3-(2-methylquinolinyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
24. (lα,5α,6α)-N-[3-(3-nitro-4-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2- cyclopentyl-2-phenylacetamide
25. (lα,5α,6α)N-[3-(3-nitro-4-hydroxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
26. (lα,5α,6α)-N-[3-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
27. (lα,5α,6α)-N-[3-(3-aminobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cy c lopenty 1 -2-pheny lacetamide
28. (lα,5α,6α)-N-[3-(6-aminopyridin-2-yl-methyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
29. (lα,5α,6α)-N-[3-(2-phenoxyethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cy c lopenty 1-2-pheny lacetamide
30. (lα,5α,6α)-N-[3-(3-phenoxypropyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
31. (lα,5α,6α)-N-[3-(2-methylpyrollyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
32. (lα,5α,6α)-N-[3-[(l,4-benzodioxan-6-yl)-methyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
33. (lα,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-
phenylacetamide
34. (lα,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclobutyl-2-phenylacetamide
35. (lα,5α,6α)-N-[3-(2-(3,4-methylendioxyphenyl)ethyl]-3-azabicyclo-[3.1.0]hex-6-yl]-
2-hydroxy-2-cyclobutyl-2-phenylacetamide
36. (lα,5α,6α)-N-[3-benzyl-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-
phenylacetamide
37. ((lα,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopropyl-2-phenylacetamide
38. (lα,5α,6α)-N-[3-[2-(3,4-methylenedioxyphenyl)ethyl]-3-azabicyclo-[3.1.0]hex-6-yl]-
2-hydroxy-2-cyclopropyl-2-phenylacetamide
39. (lα,5α,6α)-N-[3-(4-hydroxy-3-methoxybenzyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide


40. (lα,5α,6α)-N-[3-(3-hydroxy-4-methoxybenzyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
41. (lα,5α,6α)-N-[3-(2-phenylcarboethoxyethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
42. (lα,5α,6α)-N-[3-[l-(2-hydroxyphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
43. (lα,5α,6α)N-[3-[l-(4-methylphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
44. (lα,5α,6α)-N-[3-(phenylmethylpyridine)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
45. (lα,5α,6α)-N-[3-(4-pyridylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
46. (lα,5α,6α)-N-[3-(l-indanyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-
2-phenylacetamide
47. (lα,5α,6α)-N-[3-(3-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
48. (lα,5α,6α)-N-[3-(2,4,6-trimethylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopenty 1-2-pheny lacetamide
49. (lα,5α,6α)-N-[3-(2-(3,4-dimethoxyphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
50. (lα,5α,6α)-N-[3-(2-(3,4-dimethylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
51. (lα,5α,6α)-N-[3-pentyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-
phenylacetamide
52. (lα,5α,6α)-N-[3-(4-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
53. (lα,5α,6α -N-[3-(2-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
54. (lα,5α,6α -N-[3-(2,3,4,5,6-pentafluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
55. (lα,5α,6α -N-[3-(4-cyanobenzyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-
cy c lohexy 1-2-pheny lacetam ide
56. (lα,5α,6α -N-[3-(3-methylpyridyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
57. (lα,5α,6α -N-[3-(4-bromo-2-methylthienyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
58. (lα,5α,6α -N-[3-[l-(phenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
59. (lα,5α,6α -N-[3-(2-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide


60. (lα,5α,6α -N-[3-(4-methoxycarbonyl]benzyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
61. (lα,5α,6α -N-[3-(diphenylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
62. (lα,5α,6α -N-[3-(4-carboxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
63. (lα,5α,6α -N-[3-(2-aminobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
64. (lα,5α,6α -N- [3 -(2-carboethoxypropy l)-3 -azabicyc lo [3.1.0] hex-6-y 1] -2-hydroxy-2-
cyclopentyl-2-phenylacetamide
65. (lα,5α,6α -N-[3-(2-(4-acetylphenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
66. (lα,5α,6α -N-[3-(2-(4-methoxycarbonyl)phenyl)ethyl-3-azabicyclo[3.1.0]hex-6-yl]-
2-hydroxy-2-cyclopentyl-2-phenylacetamide
67. (lα,5α,6α -N-[3-(3-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
68. (lα,5α,6α -N-[3-(2-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
69. (lα,5α,6α N-[3-(3-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
70. (lα,5α,6α -N-[3-(3-methylbutyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
71. (lα,5α,6α -N-[3-(4-hydroxymethylphenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
72. (lα,5α,6α -N-[3-(3-Fluoro-4-aminobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
73. (lα,5α,6α -N-[3-(l-(3,4-dimethylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
74. (lα,5α,6α -N-[3-(2-(3-methylphenoxy)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
75. (lα,5α,6α -N-[3-(3-(3-methylphenoxy)propyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
76. (lα,5α,6α -N-[3-(2-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
77. (lα,5α,6α -N-[3-(2-(2-methylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
78. (lα,5α,6α -N-[3-[(l,3-dioxolan-2-yl)-methyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
79. (lα,5α,6α -N-[3-[(2-carboxy)propyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopenty 1-2-pheny lacetamide


80. (lα,5α,6α -N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2,2-
diphenylacetamide
81. (lα,5α,6α -N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cycloheptyl-2-phenylacetamide
82. (lα,5α,6α -N-[3-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-
2-hydroxy-2-cyclopropyl-2-phenylacetamide
83. (lα,5α,6α -N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopropy 1-2-pheny lacetamide
84. (lα,5α,6α N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclobutyl-2-phenylacetamide
85. (lα,5α,6α -N-[3-[(2-phenylcarboxy)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cycloheptyl-2-phenylacetamide
86. (lα,5α,6α -N-[3-(2-(3-indoyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
87. (lα,5α,6α -N-[3-(2-methylnaphthyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lohexy 1-2-pheny lacetamide
88. (lα,5α,6α -N-[3-(2-(indoyl-3-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
89. ((lα,5α,6α -N-[3-hexyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-
phenylacetamide
90. (lα,5α,6α -N-[3-(l,2,3,4-tetrahydronaphth-l-yl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
91. (lα,5α,6α -N-[3-(2-chlorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopenty 1-2-pheny lacetamide
92. (lα,5α,6α -N-[3-(2-(2-methoxyphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
93. (lα,5α,6α -N-[3-(2-(4-fluorophenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
94. (lα,5α,6α -N-[3-[l-(indan-5-yl)ethyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
95. (lα,5α,6α -N-[3-(l-(naphth-l-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
96. (lα,5α,6α N-[3-(l-(3,4-methylenedioxyphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-
2-hydroxy-2-cyclopentyl-2-phenylacetamide
97. (lα,5α,6α N-[3-[l-(l,2,3,4-tetrahydronaphth-6-yl)ethyl]-3-azabicyclo[3.1.0]hex-6-
yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
98. (lα,5α,6α -N-[3-[l-cis-(hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyc lopropy 1-2-pheny lacetamide
99. (lα,5α,6α N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopropyl-2-phenylacetamide


100. (lα,5α,6α)-N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0] hex-6-yl ]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
101. (lα,5α,6α -N-[3-[l-(cis-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclohexyl-2-phenylacetamide
102. (lα,5α,6α -N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
103. (lα,5α,6α -N-[3-[l-(cis-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
104. (lα,5α,6α -N-[3-(2-naphthylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
105. (lα,5α,6α -N-[3-[(2-phenyl-l-methyl-2-oxo)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
106. (lα,5α,6α N-[3-(2-(4-carbamoylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
107. (lα,5α,6α -N-[3-(2-(4-benzyloxycarbonylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-
yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
108. (lα,5α,6α -N-[3-[l-(2-methylpropyl)benzene]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
109. v(lα,5α,6α)-N-[3-[(2-phenyl-1 -methyl-2-oxo)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclohexyl-2-phenylacetamide
110. (lα,5α,6α -N-[3-hexyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-
phenylacetamide
111. (lα,5α,6α -N-[3-(2-(4-cyanophenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-
2-cyclopentyl-2-phenylacetamide
112. (lα,5α,6α -N-[3-(2-(4-sulphamoylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-
hydroxy-2-cyclopentyl-2-phenylacetamide
113. (lα,5α,6α -N-[3-cyclohexylmethyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-
cyclopentyl-2-phenylacetamide
114. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2,2-diphenylacetamide
115. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-chloro-2-cyclohexyl-2-
phenylacetamide
116. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-cyclohexyl-2-
phenylacetamide
117. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-phenylacetamide
118. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-cyclopentyl-2-
phenylacetamide
119. (lα,5α,6α -N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-phenyl
propionamide
120. N-methyl-N-(la,5a,6a)-N-[3-(l-phenyl-ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyclopentyl-2-hydroxy-2-phenylacetamide


121. N-methyl-N(lα,5α,6α )-N-[3-(3,4-methylenedioxyphenethyl)-3-azabicyclo[3.1.0]-
hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide
122. N-methyl-N-((lα,5α,6α )-N-[3-(l-benzyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyclopentyl-2-hydroxy-2-phenylacetamide
123. N-methyl(lα,5α,6α )-N-[3-(3,4-methylenedioxyphenethyl)-3-azabicyclo[3.1.0]-hex-
6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide
124. N-methyl-N-(lα,5α,6α )--N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyclohexyl-2-hydroxy-2-phenylacetamide
125. N-methyl-N(lα,5α,6α )--N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyclopentyl-2-hydroxy-2-phenylacetamide
126. N-rnethyl-N-((lα,5α,6α )-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyclopentyl-2-hydroxy-2-phenylacetamide L (+)tartarate salt,
Compounds or compositions disclosed may be administered to an animal for treatment orally, or by parenteral route. Pharmaceutical compositions disclosed herein can be produced and administered in dosage units, each unit containing a certain amount of at least one compound described herein and/or at least one physiologically acceptable salt addition thereof. The dosage may be varied over extremely wide limits as the compounds are effective at low dosage levels and relatively free of toxicity. The compounds may be administered in the low micromolar concentration, which is therapeutically effective, and the dosage may be increased as desired up to the maximum dosage tolerated by the patient.
The present invention also includes within its scope prodrugs of the compounds of Formulae I, II, III, IV, V and VI. In general, such prodrugs will be functional derivatives of these compounds, which readily are converted in vivo into the defined compounds. Conventional procedures for the selection and preparation of suitable prodrugs are known.
The present invention also includes the enantiomers, diastereomers, N-Oxides, polymorphs, solvates and pharmaceutically acceptable salts of these compounds as well as metabolites having the same type of activity. The present invention further includes pharmaceutical composition comprising the molecules of Formulae I, II, III, IV, V and VI or prodrugs, metabolite enantiomers, diastereomers. N-oxides, polymorphs solvates or pharmaceutically acceptable salts thereof, in combination with pharmaceutically acceptable carrier and optionally included excipient.
The examples mentioned below demonstrate the general synthetic procedure as well as the specific preparation of the preferred compound. The examples are provided to illustrate particular aspects of the disclosure and should not be constrained to limit the scope of the present invention, as defined by the claims.

EXPERIMENTAL DETAILS
Various solvents, such as acetone, methanol, pyridine, ether, tetrahydrofuran, hexanes, and dichloromethane, were dried using various drying reagents according to procedures well known in the literature. IR spectra were recorded as nujol mulls or a thin neat film on a Perkin Elmer Paragon instrument, Nuclear Magnetic Resonance (NMR) were recorded on a Varian XL-300 MHz instrument using tetramethylsilane as an internal standard.
EXAMPLE 1
Preparation of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenyl acetamide (Compound No.l)
Step-la: Synthesis of 2-Hydroxy-2-cyclopentyl-2-(4-methoxy)phenylacetic acid.
This was prepared following the procedure described in J.Amer. Chem. Soc. 75, 2654 (1953).
Step-lb: Synthesis of (la, 5a, 6a)-6-amino-3-azabicyclo[3.1.0]hexane:
This was synthesized as per reported procedure of Braish, T.F. et. al., Synlett. 1 100 (1996).
Step-lc: Synthesis of (la, 5a, 6a)-6-tert-butoxy carbonylamino-3-azabicyclo
[3.1.0]hexane.
This was synthesized as per reported procedure of Braish, T.F. et. al.,. Synlett. 1110 (1996).
Step-Id: Synthesis of (la, 5a, 6a)-N-3-(4-methyl-3-pentenyl-6-tert butoxycarbonylamino-3-azabicyclo [3.1 .OJhexane:
To a solution of compound of step-lc (Immol) in 10 ml of acetonitrile was added 5-bromo-4-methyl pent-3-ene (0.75 mmol) followed by the addition of potassium carbonate (3 mmol) and potassium iodide (2 mmol). The reaction mixture was refluxed for 5 hours and then brought to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (60 x 20 mesh size silica gel). The compound was eluted with 1:1 EtOAc :Hexane mixture.
(CDC13): 6 value: 5.09-5.04 (t, 4H), 4.56 (bs, 1H), 3.1 1-3.08 (d, 2H), 2.76 (s, 1H), 2.36-2.31 (m,4H), 2.11-2.03 (m, 2H), 1.67(s,3H), 1.52-1. 43 (m, 13H), IR(DCM):1706 cnV1
Step-le: Synthesis of (la,5a,6a)-3-N-(4-methyl-3-pentenyl)-6-amino-3-azabicyclo[3.1.0] hexane hydrochloride
To a solution of compound of step-Id in EtOAc (20 ml) at 0°C was added saturated solution of hydrochloric acid in EtOAc. The reaction mixture was stirred at room temperature for 16 hours and then concentrated under reduced pressure to give a solid.
m.p.: 231°C

Step-lf: Synthesis of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]
hex-6-yl]-2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenyl acetamide (Compound No.l)
A solution of 2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenylacetic acid (Immol) and (la, 5a, 6a)-3-N-(4-methyl-3-pentenyl)-6-amino-3-azabicyclo[3.1.0]hexane hydrochloride (Immol) in DMF (5ml) was cooled to 0°C. The reaction mixture was treated with 1-hydroxybenzotriazole (HOBT, 1.1 mmol) and N-methyl morpholine (NMM, 4mmol) and stirred at 0°C for half an hr. EDC.HCl (l-[3-(dimethylamino)propyl]-3-ethyl-carbodiimide hydrochloride; 1 mmol) was added and the reaction mixture was stirred at 0°C for 1 hr. and then at room temperature overnight. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography (100 x 200 mesh size silicagel) eluting the compound with 70:30 EtOAc-hexane mixture.
'HNMR (CDC13) 6-value): 7.54-6.84 (m, 4-Ar-H); 6.35 (bs, 1H) 5.04 (t, 1H); 3.79 (s, 3H); 3.19-1.17 (m, 26H), IR (DCM): 1652 cm"1
EXAMPLE 2
Preparation of (la, 5a, 6a)-N-[3-(2-ThienyImethyl)-3-azabicyclo[3.1.0] hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.2)
Step-2a: Synthesis of 2-hydroxy-2-cyclohexyl-2-phenylacetic acid:
This was prepared by following the procedure in J.Amer.Chem. Soc., 75, 2654 (1953).
Step-2b: Synthesis of (la, 5 a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide:
The compound was synthesized by procedure of Example 1, step-f, using 2-hydroxy-2-cyclohexyl-2-phenylacetic acid in place of 2-hydroxy-2-cyclopentyl-2-(4-methoxy) phenylacetic acid and (la,5a,6a)-3-benzyl-3-azabicyclo-6-amino [3.1.0]hexane instead of (la, 5a, 6a)-3-N-(4-methyl-3-pentenyl)-6-amino-3-azabicyclo[3.1.0]hexane hydrochloride.
Step-2c: Synthesis of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide.
The compound of Step-b (1 mmol) in MeOH (20 ml) was added to a suspension of Pd-C in MeOH (10 ml) and the reaction mixture was hydrogenated in parr apparatus at 45 psi for 3 hrs. The reaction mixture was filtered over celite and concentrated under reduced pressure to give the compound.

'HNMR (CDCl3-8 value): 7.47-6.74 (m, 5ArH), 3.24-3.16 (m, 3H), 3.07-3.02 (m, 2H), 2.9-1.23 (m, 13H), IR (DCM): 1660cm-1.
Step-Id: Synthesis of (la, So, 6a)-N-[3-(2-Thienylmethyl)-3-azabicyclo[3.1.0] hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.2)
A solution of compound of step c (Immol) and 2-formylthiophene (1.1 mmol) in dry THF was stirred over molecular sieves for 2 hours and then sodium triacetoxy borohydride was added and the reaction mixture stirred at room temperature overnight. The reaction mixture was filtered, concentrated under reduced pressure and EtOAc was added. The organic layer was washed with water, dried and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh, silica gel), eluting the compound with 40:60 EtOAc-hexane.
m.pt.: 153-154°C, ]HNMR (CDC13, 5 value): 7.59-6.81 (m, 8 ArH), 6.59 (bs, 1H); 3.73 (s, 2H), 3.12-1.23 (m, 18H), IR (KBr): 1656 cm'1
EXAMPLE 3
Preparation of (la, 5a, 6a)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.3)
Step-3a: Synthesis of 2-hydroxy-2-cyclopentyl-2-phenyl acetic acid.
This was prepared by following the procedure in J.Amer. Chem. Soc. 75, 2654 (1953).
Step-3b: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
This was synthesized by procedure of Example 2, Step b, using 2-hydroxy-2-cyclopentyl-2-phenylacetic acid in place of 2-hydroxy-2-cyclopentyl-2-(4-(methoxy)phenyl)acetic acid and (la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino [3.1.0]hexane instead of (la, 5a, 6a)-3-N-(4-methyl-3-pentyl)-6-amino-3-azabicyclo[3.1.0] hexane hydrochloride.
Step-3c: Synthesis of (la, 5a, 6a)-N-[3-azabicyclo-[3.10]hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetmide.
The compound was synthesized by following the procedure of Example-2, Step-c, but using the compound (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
Step-3d: Synthesis of (la, 5a, 6a)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.3)

The compound was synthesized by following the procedure of Example-2, Step-d, using (la, 5a, 6a)-N-[3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide.
'HNMR (CDCl3-8 values): 7.58-6.82 (m, 8ArH), 6.36 (bs, 1H), 3.74 (s, 2H), 3.11-3.10 (m, 16H), IR(DCM): 1658cm'1
EXAMPLE 4
Preparation of (la, 5a, 6a)-N-[3-(5-nitro-2-furylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.4)
A solution of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol) in THF containing acetic acid (3.7 mmol); 5-nitrofurfural (2.5 mmol) and sodium triacetoxyborohydride (3.2 mmol) was stirred at room temperature overnight. The reaction mixture was poured into saturated bicarbonate solution and extracted with EtOAc. The organic layer was washed with water and dried. The crude compound obtained after removing the solvents was purified by column chromatography (100-200 mesh silica gel) eluting the compound with 20:80 EtOAc:Hexane mixture.
'HNMR (CDCl3S-value): 7.58-7.23 (m, 5ArH), 6.44 (bs, 1H); 6.37 (d, 1H), 3.66 (s, 2H), 3.14-2.90 (m, 5H), 2.52-2.48 (m, 2H), 1.60-1.47 (m, 8H), 1.46-1.42 (m, 2H), IR (DCM):
1655cm'1
EXAMPLE 5
Preparation of (la, 5a, 6a)-N-[3-(4-methyl-pentyI)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.5)
A solution of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol) in 15 ml of acetonitrile containing 4-methylpentyl methanesulphonate (2 mmol) and potassium carbonate (2 mmol) was refluxed for 8 hours. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh, silicagel) eluting the compound with 80: 20: EtOAc-hexane mixture.
'HNMR (CDC13, 8 value): 7.63-7.26 (m, 5ArH); 6.37 (bs, 1H), 3.14-3.07 (m, 4H); 2.85 (s, 1H); 2.33-2.28 (m, 3H), 1.7-0.82 (m, 21H), IR(DCM): 1651 cm'1
EXAMPLE 6
Preparation of (la, 5a, 6a)-N-[3-(2-(l,4-benzodioxan-6-yl)ethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.6)
Step-6a: Synthesis of 6-(2-bromoethyl)-1,4-benzodioxan0

The compound was synthesized following the procedure of EP 0388054 Al.
Step-6b: Synthesis of (la, 5a, 6a)-N-[3-(2-(l,4-benzodioxan-6-yl)ethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
The compound was synthesized following the procedure of Example-5 using 6-(2-bromoethyl)-l,4-benzodioxan, instead of 4-methylpentyl methane sulphonate.
'HNMR (CDC13, 8 values): 7.60-7.23 (m, 5ArH), 6.76-6.56 (m, 3H), 5.30 (s, 1H), 4.22 (s, 4H), 3.24-2.57 (m, 10H), 1.67-0.89 (m, 10H), IR (DCM): 1661 cnV1
EXAMPLE 7
Preparation of (la, Sa, 6a)-N-[3-(3,4,5-trimethoxyphenethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.7)
Step-7a: Synthesis of 3,4,5-trimethoxyphenethylbromide.
The compound was synthesized following the procedure described in EP 0388054 Al and starting with 3,4,5-trimethoxyphenylacetic acid.
Step-7b: Synthesis of (la, 5a, 6a)-N-[3-(3,4,5-trimethoxyphenethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
The compound was synthesized following the procedure of Example 5, using 3,4,5-trimehtoxyphenethyl bromide instead of 4-methylpentyl methane sulphonate.
'HNMR (CDC13): 7.59-6.42 (m, 7ArH), 6.37 (bs, 1H), 3.82 (s, 9H), 3.19-0.89 (m, 20H), IR
(DCM): 1653cm'1
EXAMPLE 8
Preparation of (la, Sa, 6a)-N-[3-[3-(3,4-methylenedioxyphenyl)propyl)]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 8)
The compound was synthesized by following the procedure of Example 5, using 3-(3,4-methylenedioxyphenyl)propylbromide instead of 4-methylpentyl methane sulphonate.
'HNMR (CDC13): 7.59-6.56 (m, 8ArH), 5.29 (s, 2H), 3.19-0.89 (m, 22H), IR (DCM): 1654 cm"
EXAMPLE 9
Preparation of (la, Sa, 6a)-N-[3-(3,4,5-trimethoxybenzyl)-3-azabicyclo [3.1.0] hex-6-yl]-2-hydroxy-2-cyclopenryI-2-phenylacetamide (Compound No.9)
Step-9a: Synthesis of 3,4,5-trimethoxybenzylchloride
The compound was synthesized following the procedure described in EP0388054 Al and starting with 3,4,5-trimethoxybenzoic acid.
Step-9b: Synthesis of (la, 5a, 6a)-N-[3-(3,4,5-trimethoxybenzyl)-3-azabicyclo [3.1.0] hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide

The compound was prepared by following the procedure of Example-5, using 3,4,5-trimethoxybenzylchloride instead of 4-methylpentyl methanesulphonate.
'HNMR (CDC13, 5-values): 7.59-6.46 (m, 7ArH), 6.40 (bs, 1H), 3.82 (s, 9H), 3.46 (s, 2H), 3.09-1.01 (m, 16H), IR(DCM): 1653cm'1.
EXAMPLE 10
Preparation of (la, 5a, 6a)-N-[3-(3,5-dimethoxybenzyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 10)
To a solution of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide (1 mmol), 3,5-dimethoxybenzylchloride (1.3 mmol), potassium carbonate (2 mmol) and potassium iodide (2 mmol) in acetonitrile was refluxed for 8 hours. The reaction mixture was filtered, concentrated under reduced pressure and the residue was purified by column chromatography (100-200 mesh size silicagel) eluting the compound with 1:1 EtOAc-hexane mixture.
'HNMR (CDC13, 8 values): 7.58-6.44 (m, 8ArH), 6.33 (bs, 1H), 3.76 (s, 6H), 3.52 (s, 2H), 3.11-3.10 (m, 16H)
EXAMPLE 11
Preparation of (la, 5a, 6a)-N-[3-(3,4-dimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 11)
The compound was synthesized by following the procedure of Example 10 but using 3,4-dimethoxybenzylchloride instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-values): 7.58-6.74 (m, 8ArH), 6.42 (bs, 1H), 3.84 (s, 2H), 3.49-0.89 (m, 16H),IR(DCM): 1657cm'1
EXAMPLE 12
Preparation of (la, 5a, 6a)-N-[3-(3-methoxybenzyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 12)
The compound was synthesized following the procedure of Example 10, using 3-methoxybenzylchloride instead of 3,5-dimethoxybenzylchloride.
The pure product was eluted with 20:80 EtOAc-hexane mixture.
'HNMR (CDC13, 8 values): 7.60-6.76 (m, 9Ar-H), 6.44 (bs, 1H), 3.78 (s, 3H), 3.57 (s, 2H), 3.13-0.89 (m, 16H), IR(DCM): 1661 cm'1
EXAMPLE 13
Preparation of (la, 5a, 6a)-N-[3-(4-trifluoromethyIbenzyi)-3-azabicyclo [3.1.0] hex-6-yl]-2-hydroxy-2-cyc!opentyl 2-phenyl acetamide (Compound No.13)
A solution of ((la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol), 4-trifluoromethylbenzaldehyde (2.64 mmol), sodium triacetoxyborohydride (3.3 mmol) and acetic acid (3.8 mmol) in THF was stirred at room

temperature for 4 days. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layer was washed with water, dried and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh size silicagel) and compound was eluted with 20:80 EtOAc-hexane mixture.
'HNMR (CDC13, 8-values): 7.60-7.23 (m, 9ArH), 6.49 (ds, 1H), 3.68 (s, 2H), 3.12-1.10 (m, 16H), IR(DCM): 1651cm'1
EXAMPLE 14
Preparation of (la, 5a, 6a)-N-[3-(5-methyl-2-furylmethyl)-3-azabicyclo [3.1.0], hex-6-yl]-2-hydroxy-2-cyclopenty!-2-phenylacetamide (Compound No.14)
The compound was synthesized by following the procedure of Example 13, using 5-methyl-2-furancarboxaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13> S-values): 7.57-5.99 (m, 7ArH), 5.84 (s, 1H), 3.53 (s, 2H), 3.09-2.49 (m, 7H), 2.24 (s, 3H), 1.63-1.16 (m, 9H), IR(DCM): 1638cm'1.
EXAMPLE 15
Preparation of (la, 5a, 6a)-N-[3-(2-(4-methylphenoxy)ethyl)-3-azabicycIo [3.1.0] hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.15)
The compound was synthesized by following the procedure of Example 10, using 4-methylphenoxyethyl bromide instead of 3,5-dimethoxybenzylchloride.
The compound was eluted with 30:70 - EtOAc-hexane mixture.
'HNMR (CDC13,8 values): 7.58-6.73 (m, 9ArH), 6.48 (s, 1H), 4.01 (t, 3H), 3.25-2.63 (m, 9H), 2.26 (s, 3H), 1.62-1.18 (m, 9H), IR(DCM): 1652cm'1
EXAMPLE 16
Preparation of (la, 5a, 6a)-N-[3-(3-nitrobenzyl)-3-azabicyclo[3.1.0] hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.16)
The compound was prepared by following the procedure of Example 13 but using 3-nitrobenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 8-values): 8.09-7.23 (m, 9ArH), 6.47 (bs, 1H), 3.67 (s, 2H), 3.22-1.23 (m, 16H),IR(DCM): 1654cm"1
EXAMPLE 17
Preparation of (la, 5a, 6a)-N-[3-(4-chIorophenethyl)-3-azabicyclo [3.1.0]hex-6-yi]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.17)
The compound was synthesized following the procedure of Example 5 but using 4-chlorophenylthylmethane sulphonate instead of 4-methylpentyl methanesulphonate.

'HNMR (CDC13 S-values): 7.58-7.06 (m, 9ArH), 6.39 (s, IH), 3.16-3.11 (t, 2H), 3.02-0.87 (m, 18H),IR(DCM): 1657cm'1
EXAMPLE 18
Preparation of (la, 5a, 6a)-N-[3-(4-nitrobenzyl)-3-azabicyclo [3.1.0]hex-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 18)
The compound was synthesized using the procedure of Example 10, using 4-nitrobenzyl chloride instead of 3,5-dimethoxy benzyl chloride.
m.pt: 85-87°C, 'HNMR (CDC13, 8 values): 7.58-7.06 (m, 9ArH), 6.39 (s, IH), 3.16-3.11 (t, 2H), 3.02-0.87 (m, 18H), IR (DCM): 1657cm-'
EXAMPLE 19
Preparation of (la, 5a, 6a)-N-[3-(3-phenylpropyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.19)
The compound was synthesized by following the procedure of Example 13, using phenylpropionaldehyde instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDC13, 8-values): 7.59-7.12 (m, lOArH), 6.38 (bs, IH), 3.11-1.25 (m, 22H)
EXAMPLE 20
Preparation of (la, 5a, 6a)-N-[3-(3-hydroxybenzyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.20)
The compound was synthesized by following the procedure of Example 13, using 3-hydroxybenzaldehyde instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDCb, S-values): 7.59-6.67 (m, 9ArH), 6.54 (bs, IH), 3.47 (s, 2H), 3.04-0.83 (m, 16H)
EXAMPLE 21
Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.21)
The compound was synthesized by following the procedure of Example 13, using acetophenone instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDCb, 8-values): 7.58-7.15 (m, lOArH), 6.36 (bs, IH), 3.29 (q, IH), 3.19-1.23 (m, 20H), IR (DCM): 1652cm-'
EXAMPLE 22
Preparation of (la, 5a, 6a)-N-[3-(4-t-butylbenzyl)-3-azabicycIo [3.1.0]hex-6-yI]-2-hydroxy-2-cycIopentyl-2-phenyIacetamide (Compound No.22)
The compound was synthesized by following the procedure of Example 10, using 4-t-butylbenzylbromide instead of 3,5-dimethoxybenzylbromide.

m.pt. : 60-62°C, 'HNMR (CDC13, 8-values): 7.58-7.12 (m, 9ArH), 6.35 (bs, 1H), 3.40 (s, 2H), 3.13-1.36 (m, 16H), 1.29 (s, 9H), IR(DCM): 1652cm'1
EXAMPLE 23
Preparation of (la, 5a, 6a)-N-[3-(2-methylquinolinyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopenryl-2-phenylacetamide (Compound No. 23)
The compound was synthesized by following the procedure of Example 10 but using 2-chloromethyl quinoline instead of 3,5-dimethoxybenzylbromide.
m.pt.: 54-57°C, 1HNMR(CDC13, 8-values): 8.08-7.26 (m, HArH), 6.44 (bs, 1H), 3.87 (s, 2H),3.13-1.15(m, 16H), IR(DCM): 1646cm'1
EXAMPLE 24
Preparation of (la, 5a, 6a)-N-[3-(3-nitro-4-methoxybenzyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.24)
The compound was synthesized by following the procedure of Example 13 but using 3-nitro-4-methoxybenzaldehyde instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDC13, 8-values): 7.68-6.97 (m, 8ArH), 6.46 (bs, 1H), 3.93 (s, 3H), 3.50 (s, 2H), 3.04-1.10(m, 16H),IR(DCM): 1650cm'1
EXAMPLE 25
Preparation of (la, 5a, 6a)-N-[3-(3-nitro-4-hydroxybenzyI)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.25)
The compound was synthesized by following the procedure of Example 13 but using 3-nitro-4-hydroxy benzaldehyde instead of 4-trifluoromethyl benzaldehyde.
IR (DCM): 1658cm'1, 'HNMR (CDC13, 8-values): 7.91-7.05 (m, 8ArH), 6.44 (bs, 1H), 3.49 (s,2H), 3.04-1.23 (m, 16H)
EXAMPLE 26
Preparation of (la, 5a, 6a)-N-[3-(3,4-dichlorophenyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopenryl-2-phenylacetamide (Compound No.26)
The compound was synthesized by following the procedure of Example 10, using 3,4-dichlorophenethyl methanesulphonate instead of 4-methylpentyl methane sulphonate.
'HNMR (CDC13): 7.581-6.7 (m, 8ArH), 6.39 (bs, 1H), 3.14-0.88 (m, 20H)
EXAMPLE 27
Preparation of (la, 5a, 6a)-N-[3-(3-aminobenzyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.27)
The solution of compound of Example 15 (Immol) in methanol was cooled in an ice bath and to it raney nickel and hydrazine hydrate (2 mmol) were added. The reaction mixture was further stirred for 2 hours in an ice bath. It was filtered over celite, the filtrate was

concentrated, and the residue taken in DCM. The residue was washed with water, dried and purified by column chromatography (100-200 mesh, silicagel) eluting the compound with 70:30 EtOAc-hexane mixture.
'HNMR (CDC13, 5-values): 7.59-6.52 (m, 9ArH), 6.37 (bs, 1H), 3.44 (s, 2H), 3.077-1.25 (m, 16H),IR(DCM): 1645cm'1
EXAMPLE 28
Preparation of (la, 5a, 6a)-N-[3-(6-aminopyridin-2-yl-methyI)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.28)
Step-a: Synthesis of 6-tert-butoxy carbonyl amino-2-pyridine methyl methane sulphonate
The compound was synthesized following the procedure described in J.Med.Chem., 2000, Vol. 43(26), 5017-5029
Step-b: Synthesis of (la, 5a, 6a)-N-[3-(6-tert-butoxycarbonyl aminopyridin-2-yl methyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
To a solution of compound of Step-a (1 mmol) in acetonitrile was added (la, 5a, 6a)-N-[3-(azabicyclo) [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl phenyl acetamide (1 mmol), potassium carbonate (3 mmol) and the RM was stirred overnight at RT. The RM was poured into water and extracted with EtOAc. The organic layers were dried and concentrated under reduced pressure. The residue was purified by column chromatography eluting the compound with 5:95 MeOH-DCM.
m.pt: 60°C, 'HNMR (CDC13, 8-values): 7.74-6.93 (m, 8ArH), 6.39 (bs, 1H), 3.54 (s, 2H), 3.10-2.43 (m, 6H), 1.65-1.01 (m, 19H), IR(DCM): 1658cm'1
Step-c: Synthesis of Preparation of (la, 5a, 6a)-N-[3-(6-aminopyridin-2-yl-methyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
The compound of Step-b (1 mmol) was taken in EtOAc and EtOAc saturated with hydrochloric acid was added to the RM. The RM was stirred at RT for 3 days. The RM was cooled to 0°C purified with aq. NaHCCb. The organic layer was purified by 10% MeOH-DCM.
'HNMR (CDC13): 7.59-6.33 (m, 8H), 3.57 (s, 2H), 3.14-2.44 (m, 7H), 1.89-1.15 (m, 9H)

EXAMPLE 29
Preparation of (la, 5a, 6a)-N-[3-(2-phenoxyethyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.29)
The compound was synthesized following the procedure of Example 10 but using 2-phenoxyethylbromide instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDCb, 8-values): 7.58-6.83 (m, lOArH), 6.38 (bs, IH), 3.96 (t, 2H), 3.077-1.25 (m, 16H), IR(DCM): 1645cm'1
EXAMPLE 30
Preparation of (la, 5a, 6a)-N-[3-(3-phenoxypropyi)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.30)
The compound was synthesized following the procedure of Example 10 using 3-phenoxypropylbromide instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDCb, 8 values): 7.58-6.84 (m, lOArH), 6.38 (bs, IH), 3.93 (t, 2H), 3.13-1.42 (m, 20H), IR (DCM): 1652cm"1
EXAMPLE 31
Preparation of (la, 5a, 6a)-N-[3-(2-methylpyroHyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.31)
The compound was synthesized following the procedure of Example 13 but using pyrrole-2-carboxaldehyde instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDC13, 5-values): 9.17 (s, IH), 7.58-6.05 (m, 8ArH), 5.96 (bs, IH), 3.61 (s, 2H), 3.07-1.15 (m, 16H), IR(DCM): 1645cm"'
EXAMPLE 32
Preparation of (la, 5a, 6a)-N-[3-[(l,4-benzodioxan-6-yl)-methyl]-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.32)
The compound was synthesized following the procedure of Example 13 using 1,4-benzodioxan-6-carboxaldehyde instead of 4-trifluoromethyl benzaldehyde.
m.pt: 61-64°C, 'HNMR (CDC13, 8-values): 7.57-6.65 (m, 8ArH), 6.33 (bs, IH), 4.22 (s, 4H), 3.41 (s, 2H), 3.04-1.10 (m, 16H), IR(DCM): 1655cm"'
EXAMPLE 33
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide (Compound No. 33)
The compound was prepared by the following procedure:
Step-a: Synthesis of 2-hydroxy-2-cyclobutyl-2-phenylacetic acid.
This was synthesized as per reported procedure of Saul B. Kadin and Joseph G. Cannon, J. Org. Chem., 1962, 27, 240-245.
27

Step-b: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1,0]hex-6-yl]-2-
hydroxy-2-cyclobutyl-2-phenylacetamide
This compound was prepared by following the procedure of Example 2, Step-b but using 2-hydroxy-2-cyclobutyl-2-phenylacetic acid instead of 2-hydroxy-2-cyclohexyl-2-phenyl acetic acid.
'HNMR (CDC13, 5-values): 7.47-6.19 (m, lOArH), 6.19 (bs, 1H), 3.52 (s, 2H), 3.36-3.27 (m, 1H), 3.06-2.98 (m, 3H), 2.35-2.32 (m, 2H), 1.88-1.74 (m, 8H).
EXAMPLE 34
Preparation of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicycIo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide (Compound No.34)
Step-a: Synthesis of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-cyclobutyl-2-hydroxy-2-phenylacetamide.
The compound was prepared following the procedure of Example 2, Step-c by using (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0] hex-6-yl]-2-cyclobutyl-2-hydroxy-2-phenyacetamide instead of (la, 5a, 6a)-N-[3-benzyl-3-bicyclo [3.1.0] hex-6-yl-2-cyclohexyl-2-hydroxy-2-phenylacetamide.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide
The compound was synthesized following the procedure of Example 5 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl-2-cyclobutyl-2-hydroxy-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide and 5-bromo-2-methyl-pent-3-ene instead of 4-methylpentyl methane sulphonate.
'HNMR (CDCl3,S-values): 7.48-7.26 (m, 5ArH), 6.13 (bs, 1H), 5.07-5.03 (t, 1H), 3.49 (bs, 1H), 3.34 (m, 1H), 3.10 (m, 2H), 2.86 (s, 1H), 2.33 (m, 4H), 2.09-1.57 (m, 16H), IR (DCM): 1651cm'1
EXAMPLE 35
Preparation of (la, 5a, 6a)-N-[3-[2-(3,4-methylendioxyphenyl)ethyl]-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide (Compound No. 35)
The compound was prepared by following the procedure of Example 10 but using 3,4-methylenedioxy phenethylbromide instead of 3,5-dimethoxybenzyl bromide and (la, 5a, 6a)-N-3-[azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide instead of(la,5a,6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenyl-acetamide.
'HNMR (CDC13): 7.48-7.29 (m, 5H), 6.7-6.58 (m, 3H), 6.16 (s, 1H), 5.9 (s, 2H), 3.33 (m, 1H), 3.13 (m, 2H), 2.84 (s, 1H), 2.56 (m, 4H), 2.33 (m, 2H), 2.05-1.6 (m, 8H).

EXAMPLE 36
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No.36)
Step-a: Synthesis of 2-hydroxy-2-cyclopropyl-2-phenylacetic acid.
The compound was synthesized as per reported procedure of Saul B. Kadin and Joseph G. Cannon, J.Org. Chem. 1962, 27, 240-245.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide.
The above compound was prepared by following the procedure of Example 2, Step-b using 2-hydroxy-2-cyclopropyl-2-phenylacetic acid instead of 2-hydroxy-2-cyclohexyl-2-phenylacetic acid.
'HNMR (CDC13) 6-values): 7.59-7.29 (m, 5H), 6.05 (bs, 1H), 3.54 (s, 2H), 3.06 (m, 3H), 2.37 (m, 2H), 2.04 (s, 1H), 1.54-1.45 (m, 3H), 0.54 (m, 4H), IR (DCM) : 1648 cm'1
EXAMPLE 37
Preparation of (la, 5a, 6a)-N-[3-[4-methyl-3-pentenyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No. 37)
Step-a: Synthesis of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-cyclopropyl-2-hydroxy-2-phenylacetamide.
The compound was prepared by following the procedure of Example 2 step-c, using (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo-[3.1.0]hex-6-yl]-2-cyclopropyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
The compound was synthesized following the procedure of Example 5 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-cyclopropyl-2-hydroxy-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide and 5-bromo-5-methyl-pent-3-one instead of 4-methylpentyl methane sulphonate.
'HNMR (CDC13, 5-values): 7.59-7.29 (m, 5H), 6.00 (s, 1H), 5.06 (t, 1H), 3.44 (bs, 1H), 3.12 (m, 2H), 2.94 (s,lH), 2.34 (m, 4H), 2.06 (m, 2H), 1.66-1.45 (m, OH), 0.56 (m, 4H), IR (DCM): 1651cm'1

EXAMPLE 38
Preparation of (la, 5a, 6a)-N-[3-{2-(3,4-methylenedioxyphenyl)ethyl]-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cycIopropyl-2-phenylacetamide (Compound No.38)
The compound was prepared following the procedure of Example 10 using 3,4-methylenedioxyphenethylbromide instead of 3,4-dimethoxybenzylbromide and (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
'HNMR (CDC13, 5-valus): 7.59-7.30 (m, 5H), 6.67-6.66 (m, 3H), 6.03 (s, IH), 5.9 (s, 2H), 3.17 (m, 2H), 2.92 (s,lH), 2.58 (m, 4H), 2.36 (m, 2H), 1.65-1.47 (m, 3H), 0.80 (m, IH), 0.50 (m, 4H), IR (DCM): 1649cm'1
EXAMPLE 39
Preparation of (la, 5a, 6a)-N-[3-(4-hydroxy-3-methoxybenzyl)]-3-azabicyclo[3.1.0] hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.39)
The compound was prepared following the procedure of Example 13 using 4-hydroxy-3-methoxybenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
m.pt: 68-73°C, 'HNMR (CDC13, 5 values): 7.58-6.78 (m, 8ArH), 6.66 (bs, IH), 6.41 (s, IH), 5.85 (s, 3H), 3.46 (s, 2H), 3.05-1.11 (m, 17H), IR (DCM): 1654cm'1
EXAMPLE 40
Preparation of (la, 5a, 6a)-N-[3-(3-hydroxy-4-methoxybenzyl)]-3-azabicycIo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.40)
The compound was prepared following the procedure of Example 13 using 3-hydroxy-4-methoxybenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
m.pt: 66-73°C, 'HNMR (CDC13, 8-value): 7.57-6.67 (m, 8ArH), 6.37 (bs, IH), 3.85 (s, 3H), 3.45 (s, 2H), 3.13-2.94 (m, 4H), 2.38-2.35 (m, 2H), 1.67-1.25 (m, 10H),IR (DCM): 1655cm'1
EXAMPLE 41
Preparation of (la, 5a, 6a)-N-[3-(2-phenylcarboethoxyethyl)-3-azabicycIo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.41)
The compound was synthesized following the procedure of Example 10 using 2-bromoethylphenylacetate instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, S values):7.58-7.26 (m, lOArH), 6.38 (bs, IH), 4.12-4.01 (m, 3H), 3.15-2.33 (m, 6H), 1.60-0.85 (m, 13H), IR(DCM): 1646 and 1741 cm'10

EXAMPLE 42
Preparation of (la, 5a, 6a)-N-[3-[l-(2-hydroxyphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.42)
The compound was synthesized following the procedure of Example 13 using 2-hydroxyacetophenone instead of 4-trifluoromethyl benzaldehyde.
'HNMR (CDC13, 5-values): 7.57-6.70 (m, 9ArH), 6.45 (bs, 1H), 3.38-1.16 (m, 20H), IR (DCM): 1655 cm'1
EXAMPLE 43
Preparation of (la, 5a, 6a)-N-[3-[l-(4-methylphenyi)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.43)
The compound was synthesized by following the procedure of Example 13 using 4-methylacetophenone instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 5-values): 7.58-7.04 (m, 9ArH), 6.33 (bs, 1H), 3.28-1.45 (m, 12H), 1.25-1.21 (m, 11H), IR (DCM): 1646 cm'1
EXAMPLE 44
Preparation of (la,5a,6a)-N-[3-(phenylmethylpyridine)-3-azabicyclo-[3.1.0]hex-6-yI]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.44)
The above compound was prepared by following the procedure of Example 10 using 4-(l-bromophenyl methyl)pyridine hydrochloride instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDC13, 8-values): 8.45-7.06 (m, 14ArH), 6.46 (bs, 1H), 4.17 (s, 1H), 3.12-0.91 (m, 16H),IR(DCM): 1660cm'1
EXAMPLE 45
Preparation of (la, 5a, 6a)-N-[3-(4-pyridylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.45)
The compound was synthesized following the procedure of Example 10 using 4-chloromethylpyridine hydrochloride instead of 3,5-dimethoxybenzylbromide.
m.pt: 70-73°C, 'HNMR (CDC13, 6-values): 7.40-7.16 (m, ISArH), 6.27 (bs, 1H), 3.82 (s, 1H), 3.33-1.24 (m, 11H), IR(DCM): 1657cm"'
EXAMPLE 46
Preparation of (la, 5a, 6a)-N-[3-(l-indanyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.46)
To a solution of (lot, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol) in THF was added 1-bromoindan (1.5 mmol) and N-ethyldiisopropylamine (4 mmol) under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 5 days. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was dried,

concentrated under reduced pressure and purified by column chromatography (silicagel, 100-200 mesh) eluting the compound with 30:70 EtOAc-hexane.
'HNMR (CDC13, 5-values): 7.58-7.12 (m, 9ArH), 6.36 (bs, 1H), 4.26-4.22 (t, 1H), 3.06-0.85 (m, 20H), IR (DCM): 1652 cnV1
EXAMPLE 47
Preparation of (la, 5a, 6a)-N-[3-(3-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.47)
The compound was synthesized following the procedure of Example 13 using 3-methylbenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 8-values): 7.58-6.99 (m, 9ArH), 6.36 (bs, 1H), 3.49 (s, 2H), 3.06-0.87 (m, 19H), IR(DCM): 1645cm'1
EXAMPLE 48
Preparation of (la, 5a, 6a)-N-[3-(2,4,6-trimethylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.48)
The compound was synthesized following the procedure of Example 13 using 2,4,6-trimethylbenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 8-values): 7.56-7.22 (m, 7ArH), 6.30 (bs, 1H), 3.49 (s, 2H), 3.10-0.85 (m, 25H), IR (DCM): 1646 cm'1
EXAMPLE 49
Preparation of (la, 5a, 6a)-N-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.49)
Step-a: Synthesis of 3,4-dimethoxyphenethylbromide
The compound was synthesized as per reported procedure in EP 0388054A1, using 1,2-dimethoxybenzene instead of 2,3-dihydrobenzofuran.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-[2-(3,4-dimethoxyphenyl)ethyl]-3-
azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
The compound was synthesized following the procedure described in Example 10 using 3,4-dimethoxyphenethyl bromide instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDC13, 5-values): 7.58-7.56 (d, 2ArH), 7.36-7.23 (m, 3H), 6.77-6.67 (m, 3H), 6.39 (bs, 1H), 3.88-3.83 (s, 6H), 3.18-3.15 (d, 2H), 3.15-2.37 (m, 10H), 1.73-0.87 (m, 10H), IR (DCM): 1642cm-'
EXAMPLE 50
Preparation of (la, 5a, 6a)-N-[3-[2-(3,4-dimethylphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.50)
Step-a: Synthesis of 3,4-dimethylphenethylbromide.
The compound was synthesized as per reported procedure in EP0388054A1 using o-xylene instead of 2,3-dihydrobenzofuran.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-[2-(3,4-dimethylphenyl)ethyl]-3-azabicyclo[3.1.0] hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
The compound was synthesized following the procedure described in Example 10 using 3,4-dimethylphenethyl bromide instead of 3,5-dimethoxy benzylbromide.
'HNMR (CDC13): 7.58-7.56 (d, 2ArH), 7.38-7.28 (m, 2ArH), 7.28-6.36 (m, 2ArH), 7.02-7.00 (d, lArH), 6.92-6.87 (m, 2ArH), 6.36 (bs, 1H), 3.16-3.13 (m, 3H), 3.02-2.99 (m, 1H), 2.85 (bs, 1H), 2.63-2.53 (m, 4H), 2.37-2.34 (m, 2H), 2.20 (bs, 6H), 1.63-1.25 (m, 11H), IR (DCM): 1646cm-1
EXAMPLE 51
Preparation of (la, 5a, 6a)-N-[3-pentyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenyIacetamide (Compound No.51)
The compound was synthesized following the procedure of Example 10, using 1-bromopentane instead of 3,5-dimethoxybenzylchloride.
'HNMR(CDC13, 8-values): 7.58-7.55 (d, 2ArH), 7.35-7.22 (m, 3H), 6.35 (bs, 1H), 3.09-3.06 (m, 3H), 2.98 (m, 1H), 2.85 (bs, 1H), 2.31-2.27 (m, 4H), 1.77-0.83 (m, 7H)
EXAMPLE 52
Preparation of (la, 5a, 6a)-N-[3-(4-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.52)
The compound was prepared following the procedure of Example 10, using 4-cyanobenzylbromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-values): 7.58-7.53 (m, 4ArH), 7.34-7.26 (m, 5ArH), 6.47 (bs, 1H), 3.57 (s, 2H), 3.06-2.97 (m, 4H), 2.35 (d, 2H, J=7.6), 1.64-1.45 (m, 8H), 1.25-1.16 (m, 2H), IR (KBr): 1652cm'1, 2228cm'1
EXAMPLE 53
Preparation of (la, 5a, 6a)-N-[3-(2-cyanobenzyl)-3-azabicycIo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.53)
To a solution of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol) in DMF (10 ml) was added 2-cyanobenzylbromide (1.2 mmol), potassium carbonate (2 mmol) and potassium iodide (2 mmol). The reaction mixture was stirred overnight at room temperature, poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh silica gel) eluting the compound with 25.75 EtOAc-hexane mixture.'HNMR (CDC13, S-value): 7.59-7.23 (m, lOArH), 6.40 (bs, IH), 3.73 (s, 2H), 3.09-2.96 (m, 5H), 2.48-2.43 (m, 2H), 1.55-1.25 (m, 8H), 1.30-1.25 (m, 2H),IR (KBr): 1651cm'1, 2225cm'1
EXAMPLE 54
Preparation of (la, 5a, 6a)-N-[3-(2,3,4,5,6-pentafluorobenzyl)-3-azabicyclo [3.1.0]hex-6-yl)-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.54)
The compound was synthesized following the procedure of Example 10 using 2,3,4,5,6-pentafluorobenzylbromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-valuesV 7.57-7.22 (m, 5ArH), 6.38 (s, IH), 3.72 (s, 2H), 3.05-1.23 (m, 16H),IR(KBr): 1653cm'1
EXAMPLE 55
Preparation of (la, 5a, 6a)-N-[3-(4-cyanobenzyI)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.55)
The compound was prepared following the procedure of Example 53, using 4-cyanobenzylbromide instead of 2-cyanobenzylbromide.
m.pt.: 66°C, 'HNMR (CDC13, 6-value): 7.66-7.46 (m, 4ArH), 7.33-7.26 (m, 5ArH), 6.66 (bs, IH), 3.57 (s, 2H), 3.07-2.98 (m, 3H), 2.69 (m, IH), 2.44-2.33 (m, 3H), 1.81-1.77 (m, IH), 1.46-1.43 (m, 2H), 1.25-1.11 (m, 7H), 0.90-0.82 (m, 2H), IR(KBr): 1655cm'1, 2228cm'1
EXAMPLE 56
Preparation of (la, 5a, 6a)-N-[3-(3-methylpyridyl)-3-azabicycIo [3.1.0]hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.56)
The compound was prepared following the procedure of Example 10, using 3-chloromethylpyridine hydrochloride instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-value): 8.45-7.18 (m, 9 ArH), 6.44 (bs, IH), 3.53 (s, 2H), 3.05-1.17 (m, 16H),IR(KBr): 1653cm'1
EXAMPLE 57
Preparation of (la, 5a, 6a)-N-[3-(4-bromo-2-methylthienyl)-3-azabicyclo [3.1.0]hex-6-yI]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.57)
The compound was prepared following the procedure of Example 13, using 4-bromo-thiophene-2-carboxaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 8-values): 7.58-6.74 (m, 7ArH), 6.40 (bs, IH), 3.74 (s, 2H), 3.13-1.10 (m, 16H), IR(KBr): 1653cm'1
EXAMPLE 58
Preparation of (la, 5a, 6a)-N-[3-[l-(phenyl)ethyi]-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyI-2-phenylacetamide (Compound No.58)
The compound was prepared following the procedure of Example 10, using 1-phenylethyl bromide instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDC13) 6-values): 7.59-6.17 (m, lOArH), 6.57 (bs, 1H), 4.13-4.10 (Q, 1H), 3.28-0.87 (m, 21H), IR (DCM) : 1659cm'1
EXAMPLE 59
Preparation of (la, 5a, 6a)-N-[3-[2-nitrobenzyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.59)
The compound was prepared following the procedure of Example 13, using 2-nitrobenzaldehyde instead of 4-trifluoromethylbenzyldehyde.
m.pt: 161-163°C, 'HNMR (CDC13, 8-values): 7.81-7.23 (m, 9ArH), 6.38 (bs, 1H), 3.84 (s, 2H), 3.08-1.25 (m, 16H), IR (DCM): 1640cm'1
EXAMPLE 60
Preparation of (la, 5a, 6a)-N-[3-[4-methoxycarbonyl]benzyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.60)
The compound was synthesized following the procedure of Example 10, using methyl-4-(bromomethyl)benzoate instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 5-values): 7.94-7.23 (m, 9ArH), 6.40 (bs, 1H), 3.89 (s, 3H), 3.57 (s, 2H), 3.07-0.82 (m, 16H), IR (DCM): 1643cm'1
EXAMPLE 61
Preparation of (la, 5a, 6a)-N-[3-[diphenylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenyIacetamide (Compound No.61)
The compound was synthesized following the procedure of Example 10, using benzhydry 1 bromide instead of 3,5-dimethoxybenzylchloride.
1 HNMR (CDC13) 6-values): 7.59-7.10 (m, 15ArH), 6.39 (bs, lH),4.16(s, 1H), 3.13-0.82 (m, 16H), IR(DCM): 1652cm'1
EXAMPLE 62
Preparation of (la, 5a, 6a)-N-[3-(4-carboxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.62)
The solution of compound (la, 5a, 6a)-N-[3-(4-carbomethoxybenzyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (1 mmol) in methanol (20 ml) containing lithium hydroxide (4 mmol) in 5 ml of water was stirred at room temperature for 24 hours. The reaction mixture was concentrated under reduced pressure, the residue was cooled in ice and acidified with acetic acid. It was extracted with ethyl acetate and the residue after removing the solvent was purified by column chromatography (100-200 mesh silicagel) eluting the compound with ethyl acetate.
m.pt: 124°-129°C, 'HNMR (DMSO-d6, 5-values): 7.88-7.21 (m, 9ArH), 5.46 (s, 1H), 3.59 (s, 2H), 2.94-1.18 (m, 16H), IR (DCM): 1656cm'f
EXAMPLE 63
Preparation of (la, 5a, 6a)-N-[3-(2-aminobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.63)
The compound was synthesized following the procedure of Example 27, using (la, 5a, 6a)-
N-[3-(2-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-
phenylacetamide.
m.pt: 67-72°C, 'HNMR (CDC13> 8-values): 7.58-6.56 (m, 9ArH), 6.43 (bs, IH), 3.51 (s, 2H), 3.02-0.83 (m, 16H), IR (DCM): 1647 cm'1
EXAMPLE 64
Preparation of (la, 5a, 6a)-N-[3-(2-carboethoxypropyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.64)
The compound was synthesized following the procedure of Example 46, using ethyl-2-bromopropionate instead of 1 -bromoindan.
'HNMR (CDC13) 5-values): 7.58-7.23 (m, 5ArH), 6.38 (bs, IH), 4.15-4.07 (q, 2H), 3.28-1.21 (m,23H), IR(DCM): 1652cm"' and 1731 cm0
EXAMPLE 65
Preparation of (la, 5a, 6a)-N-[3-(2-(4-acetyIphenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyc!opentyl-2-phenylacetamide (Compound No.65)
The above compound was prepared by following the procedure of Example 53, using 2-(4-acetylphenyl)ethylbromide instead of 2-cyanobenzylbromide.
'HNMR (CDC13, 5-values): 8.09-7.83 (m, 2ArH), 7.59-7.56 (m, 2ArH), 7.36-7.22 (m, 5ArH), 6.39 (bs, IH), 3.76-3.16 (m, 2H), 3.14-2.83 (m, 3H), 2.75-2.63 (m, 4H), 2.58-2.57 (bs, 3H), 2.36 (bs, 2H), 1.67-0.87 (m, 10H), IR (DCM): 1662 cm'1
EXAMPLE 66
Preparation of (la, 5a, 6a)-N-[3-(2-(4-methoxycarbonyl)phenyl)ethyl-3-azabicyclo[3.1.0]hex-6-yI]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.66)
The compound was synthesized by following the procedure of Example 10, using 4-methoxycarbonyl phenethylbromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, S-values): 7.93-7.90 (d, 2H), 7.58-7.56 (d, 2H), 7.35-7.30 (m, 2H), 7.27-7.20 (m, 3H), 6.36 (bs, IH), 3.88 (s, 3H), 3.15-3.12 (d, 2H), 3.09 (bs, IH), 3.01-2.99 (m, IH), 2.82 (bs, IH), 2.75-2.71 (m, 2H), 2.64-2.59 (m, 2H), 2.37-2.34 (m, 2H), 1.63-1.16 (m, 11H), IR (DCM) : 1654 cm'1 and 1720 cm'1
EXAMPLE 67
Preparation of (la, 5a, 6a)-N-[3-[3-cyanobenzyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.67)
The compound was synthesized following the procedure of Example 53, using 3-cyanobenzylbromide instead of 2-cyanobenzylbromide.
'HNMR (CDC13, 6-values): 7.59-7.46 (m, 5ArH), 7.38-7.23 (m, 4ArH), 6.41 (bs, 1H), 3.54 (s, 2H), 3.05-2.95 (m, 5H), 2.38-2.34 (m, 2H), 1.68-1.41 (m, 8H), 1.20-1.17 (m, 2H), IR
(DCM): 1648 cm'1 and 2229 cm"
EXAMPLE 68
Preparation of (la, 5a, 6a)-N-[3-[2-cyanobenzyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.68)
The compound was synthesized following the procedure of Example 53, using (la, 5a, 6a)-N-[3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
'HNMR (CDCb, 8-values): 7.58-7.24 (m, 9ArH), 6.65 (bs, 1H), 3.73 (s, 2H), 3.10-2.73 (m, 3H), 2.48 (m, 1H), 2.46-2.42 (m, 3H), 1.68-1.65 (m, 1H), 1.62 (m, 9H), 0.99-0.95 (m, 2H).
IR (DCM): 1648 cm'1 and 2224 cm'1
EXAMPLE 69
Preparation of (la, 5a, 6a)-N-[3-(3-cyanobenzyl)-3-azabicycIo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.69)
The compound was synthesized following the procedure of Example 53, using (la, 5a, 6a)-N-[3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and 3-cyanobenzyl bromide instead of 2-cyanobenzylbromide.
m.pt: 68-70°C, 'HNMR (CDC13, 8-values): 7.59-7.46 (m, 5ArH), 7.38-7.22 (m, 4ArH) 6.63 (bs, 1H), 3.54 (s, 2H), 3.06-2.97 (m, 3H), 2.68 (m, 1H), 2.39-2.34 (m, 3H), 1.81-1.77 (m, 1H), 1.66-1.16 (m, 9H), 0.87-0.83 (m, 2H), IR (DCM): 1654 cm'1 and 2229 cm'1
EXAMPLE 70
Preparation of (la, 5a, 6a)-N-[3-(3-methylbutyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.70)
The compound was synthesized following the procedure of Example 53, using (la, 5a, 6a)-N-[3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and l-bromo-3-methylbutane instead of 2-cyanobenzyl bromide.

'HNMR (CDC13, S-values): 7.59-7.56 (m, 2ArH), 7.35-7.22 (m, 3ArH), 6.56 (bs, IH), 3.07 (t, 2H), 2.85-2.80 (m, 2H), 2.35-2.25 (m, 5H), 1.66-1.62 (m, IH), 1.41-1.16 (m, 12H), 0.91-0.88 (m, 2H), 0.83 (d, 6H, J=6.0 Hz), IR (DCM): 1655 cm'1
EXAMPLE 71
Preparation of (la, 5a, 6a)-N-[3-(4-hydroxymethylphenethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.71)
Step-a: Synthesis of 4-hydroxymethylphenethyl chloride.
The compound was prepared following the procedure given in U.S. Patent No. 4,595,690. Step-b: The title compound was synthesized following the procedure of Example 10, using 4-hydroxy methylphenethylchloride instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13): 7.58-7.56 (m, 2ArH), 7.36-7.24 (m, 5H), 7.16-7.13 (d, 2H), 6.40 (bs, IH), 4.64 (s, 2H), 3.17-3.10 (m, 3H), 3.02-2.97 (m, IH), 2.84 (bs, IH), 2.67-2.62 (m, 4H), 2.41 (bs,2H), 1.77-1.16 (m, 11H), IR (DCM): 1655cm'1
EXAMPLE 72
Preparation of (la, 5a, 6a)-N-[3-(3-fluoro-4-aminobenzyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.72)
Step-a: Synthesis of 4-tert butoxy carboxylamino-3-fluorobenzylbromide
The compound was synthesized following the procedure described in J.Med.Chem., 2000,
43(26), 5017-5029
Step-b: Synthesis of (la, 5a, 6a)-N-[3-(3-fluoro-4-tert-butoxy)carbonylamino-3-
fluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentylphenylacetamide
The compound was synthesized following the procedure of Example 10, using 4-tert-butoxycarbonylamino-3-fluorobenzylbromide instead of 3,5-dimethoxybenzylchloride
Step-c: Synthesis of (la, 5a, 6a)-N-[3-(3-fluoro-4-aminobenzyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
The compound of Step-b was dissolved in EtOH and ethanolic hydrochloric acid (5 ml) was added to the RM. The RM was stirred overnight at RT. The RM was concentrated under reduced pressure to give the desired product.
'HNMR(CDC13) 8-values): 7.58-7.55 (m, 2ArH), 7.35-7.55 (m, 2ArH), 7.35-7.22 (m, 3ArH), 6.87-6.63 (m, 3ArH), 6.34 (bs, IH), 3.62 (bs, 2H), 3.49 (b, 2H), 3.10 (bs, IH), 3.04-2.95 (bs, 4H), 2.33-2.30 (m, 2H), 1.63-0.88 (m, 10H), IR (DCM): 1640cm'1
EXAMPLE 73
Preparation of (la, 5a, 6a)-N-[3-[l-(3,4-dimethylphenyl)-ethyl]-3-azabicycio [3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.73)
The compound was synthesized following the procedure of Example 10, using l-(3,4-dimethylphenyi)ethylbromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13 8-values): 7.63-6.92 (m, 8ArH), 6.34 (bs, IH), 3.27-3.25 (q,l H), 3.14-0.85 (m, 25H), IR (DCM): 1658 cm'1
EXAMPLE 74
Preparation of (la, 5a, 6a)-N-[3-[2-(3-methylphenoxy)ethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.74)
The compound was synthesized following the procedure of Example 10, using 2-(3-methylphenoxy)ethyl bromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-values): 7.58-6.64 (m, 9ArH), 6.37 (s, IH), 3.97-3.93 (t, 2H), 3.18-1.17 (m, 21H), IR (DCM): 1658 cnV1
EXAMPLE 75
Preparation of (la, 5a, 6a)-N-[3-[3-(3-methylphenoxy)propyl]-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.75)
The compound was synthesized following the procedure of Example 10, using 3-(3-methylphenoxy) propylbromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, S-values): 7.58-6.65 (m, 9ArH), 6.35 (bs, IH), 3.94-3.89 (t, 2H), 3.12-1.25 (m, 23H), IR (DCM): 1657 cm'1
EXAMPLE 76
Preparation of (la, 5a, 6a)-N-[3-(2-methylbenzyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyc!opentyl-2-phenylacetamide (Compound No.76)
The compound was prepared following the procedure of Example 13, using 2-methylbenzaldehyde instead of 4-trifluoromethylbenzaldehyde.
'HNMR (CDC13, 8-values): 7.58-7.08 (m, 9ArH), 6.35 (bs, IH), 3.49 (s, 2H), 3.09-0.88 (m, 19H), IR(DCM): 1653cm'1
EXAMPLE 77
Preparation of (la, 5a, 6a)-N-[3-(2-(2-methylphenyl)ethyl-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenyiacetamide (Compound No.77)
The compound was prepared following the procedure of Example 10, using 2-(2-methy Ipheny l)ethy Ibromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-values): 7.59-7.09 (m, 9ArH), 6.35 (bs, IH), 3.19 (m, 10H), 2.27 (8, 3H), 160-1.25 (m, 1 OH), IR (DCM): 1654 cm'1
EXAMPLE 78
Preparation of (la, 5a, 6a)-N-[3-[(l,3-dioxolan-2-yl)methyl]-3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.78)
The compound was synthesized by following the procedure of Example 10, but using 2-bromomethyl-1,3-dioxolane instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDCb, 8-values): 7.57-7.22 (m, 5ArH), 6.39 (bs, 1H), 4.90 (t, 1H), 3.95-3.79 (m, 4H), 3.22-1.18 (m, 19H), IR(DCM): 1652cm'1
EXAMPLE 79
Preparation of (la, 5a, 6a)-N-[3-[2-(carboxy)propyl]3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.79)
The compound was synthesized by following the procedure of Example 62, using (la, 5a, 6a)-N-[3-[2-(carboethoxy)propyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-(4-carbomethoxy) benzyl-3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
m.pt: 91-95°C, 'HNMR (CDCb, 5-value): 7.68-7.17 (m, 5ArH), 3.57-2.68 (m, 10H), 1.88 (s, 3H), 1.47-0.83 (m, 9H), IR(KBr): 1627cm'1 and 1714 cm'1
EXAMPLE 80
Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2,2-diphenylacetamide (Compound No.80)
Step-a: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-
hydroxy-2,2-diphenylacetamide
The compound was synthesized by following the procedure of Example 1, using 2,2-diphenylacetic acid instead of 2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenylacetic acid and (la, 5a, 6a)-3-azabicyclo-[3.1.0]-hexane instead of (la, 5a, 6a)-N-[3-[4-methyl-3-pentenyl]-6-amino-3-azabicyclo-[3.1.0]hexane ]hydrochloride.
Step-b: Synthesis of (la, 5 a, 6a)-N-[3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2,2-
diphenylacetamide.
The compound was synthesized following the procedure of Example 2, Step-c, using (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2,2-diphenylacetamide instead of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide.
Step-c: Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]-hex-6-
yl]-2-hydroxy-2,2-diphenylacetamide
A solution of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2,2-diphenylacetamide (1 mmol), 1-phenylethylbromide (1.2 mmol), potassium carbonate (2 mmol) and potassium iodide (2 mmol) in 10 ml of acetonitrile was refluxed for 8 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by column chromatography (100-200 mesh silicagel) eluting the compound with 60:40- EtOAc-hexane mixture.
m.pt: 70-73°C, 'HNMR (CDC13, 6-values): 7.40-7.16 (m, 15ArH), 6.27 (bs, 1H), 3.82 (s, 1H), 3.33-3.21 (m, 3H), 3.19-3.13 (d, 1H), 2.81-2.39 (m, 2H), 1.56-1.24 (m, 5H).
EXAMPLE 81
Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycloheptyI-2-phenylacetamide (Compound No.81)
Step-a: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycloheptyl-2-phenylacetamide.
The compound was synthesized following the procedure of Example 1 using 2-hydroxy-2-cycloheptyl-2-phenylacetic acid instead of 2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenylacetic acid and (la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino-[3.1.0]hexane instead of (la, 5a, 6a)-N-[4-methyl-3-pentenyl)]-6-amino-3-azabicyclo [3.1.0]hexane hydrochloride.
Step-b: Synthesis of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-
cy c lohepty 1-2-pheny lacetam ide.
The compound was synthesized following the procedure of Example 2, Step-c, using (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycloheptyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycIohexyl-2-phenylacetamide.
Step-c: Synthesis of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-
2-hydroxy-2-cycloheptyl-2-phenylacetamide.
The compound was synthesized following the procedure of Example 80, Step-c, using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycloheptyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2,2-diphenylacetamide.
'HNMR (CDC13, 5-values): 7.60-7.14 (m, lOArH), 6.54 (bs, 1H), 3.28-3.16 (m, 2H), 2.98 (s, 1H, IR(DCM): 1652cm"1
EXAMPLE 82
Preparation of (la, 5a, 6a)-N-[3-(2-(2,3-dihydrobenzofuran -5-yl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No.82)
The compound was synthesized following the procedure of Example 5, using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopropyl-2-hydroxy-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenyl acetamide and 5-(2-bromoethyl)-2,3-dihydrobenzofuran instead of 4-methylpentylmethane sulphonate.
'HNMR (CDC13, 5-values): 7.58-7.34 (m, 5ArH), 6.99 (bs, IH), 6.88 (d,J=8Hz, IH), 6.67 (d, J=8Hz, IH), 6.03 (m, IH), 4.54 (t, 2H), 3.15 (m, 4H), 2.59-2.38 (m, 6H), 1.8 (m, IH), 1.47 (m, 2H), 1.28 (m, IH), 0.56 (m, 4H), IR (DCM): 1665cm-1
EXAMPLE 83
Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No. 83)
The compound was synthesized following the procedure of Example 5 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopropyl-2-hydroxy-2-phenylacetamide and 1-phenyl ethyl bromide instead of 4-methylpentylmethane sulphonate.
'HNMR (CDC13, 8-values): 7.58 (m, 2H), 7.38-7.17 (m, 8H), 5.99 (bs, IH), 3.40 (d, J=3.0, IH), 3.31 (m, IH), 3.20 (q, J=6.5, IH), 3.06 (m, IH), 2.78 (m, IH), 2.4 (m, IH), 2.15 (m, IH), 1.50 (m, 2H), 1.4(m, IH), 1.25 (d, J=6.5, 3H), 0.56 (m, 4H), IR (KBr): 1655cm'1
EXAMPLE 84
Preparation of (la, 5a, 6a)-N-[3-(l-phenylethyl)-3-azabicycIo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide (Compound No.84)
The compound was synthesized following the procedure of Example 80, Step-c using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2,2-diphenyl acetamide.
'HNMR (CDC13, S-values): 7.46-7.15 (m, lOArH), 6.15 (m, IH), 3.28 (m, 2H), 3.19 (q, J=6.5; IH), 2.98 (m, IH), 2.76 (m, IH), 2.4 (m, IH), 2.15-1.8 (m, 3H), 1.42 (m, IH), 1.28 (m, 8H),IR(DCM): 1655cm'1
EXAMPLE 85
Preparation of (la, 5a, 6a)-N-[3-(2-phenylcarboxyethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycloheptyI-2-phenylacetamide (Compound No.85)
The compound was prepared following the procedure of Example 63 using (la, 5a, 6a)-N-[3-(2-phenylcarboxyethyl)-3 azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohepty 1-2-phenylacetamide.
'HNMR (DMSO d6, 8-values): 7.68-7.18 (m, lOArH), 5.75 (s, IH), 3.35-2.59 (m, 7H), 1.98 (m, 2H), 1.47-1.15 (m, 9H), IR(DCM): 1638cm'1
EXAMPLE 86
Preparation of (la, 5a, 6a)-N-[3-(2-(3-indoyl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.86)
The compound was synthesized following the procedure of Example 53 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-
[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and 3-(2-bromoethyl)indole instead of 2-cyanobenzyl bromide.
'HNMR (CDC13> 5-values): 7.96 (m, IH), 7.60-7.01 (m, lOArH), 6.60 (bs, IH) 3.20 (t, 2H), 2.95-2.68 (m, 6H), 2.39 (m, 3H), 1.32-1.12 (m, 10H), 0.87-0.85 (m, 2H),IR (DCM): 1662cm'1
EXAMPLE 87
Preparation of (la, 5a, 6a)-N-[3-(2-methylnaphthyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyck>hexyI-2-phenylacetamide (Compound No.87)
The compound was synthesized following the procedure of Example 54 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and 2-(bromomethyl)naphthalene instead of 2-cyanobenzyl bromide.
m.pt: 165-168°C, 'HNMR (CDC 135-values): 7.78-7.72 (m, 3ArH), 7.63-7.57 (m, 3ArH), 7.44-7.31 (m, 6H), 6.59 (bs, IH), 3.69 (s, 2H), 3.12-3.04 (m, 3H), 2.72 (m, IH), 2.40(m, 3H), 1.82-1.78 (m, IH), 1.66-1.54 (m, 2H), 1.45-1.12 (m, 8H), 0.88-0.84 (m, IH), IR(KBr): 1653cm'1
EXAMPLE 88
Preparation of (la, 5a, 6a)-N-[3-(2-(indol-3-yl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 88)
The compound was synthesized following the procedure of Example 54 using 3-(2-bromoethyl) indole instead of 2-cyanobenzyl bromide.
m.pt.: 55-57°C, 'HNMR (CDC13, 8-values): 8.07-8.01 (m, IH), 7.65-7.60 (m, 3ArH), 7.42-7.05 (m, 7H), 6.44 (bs, IH), 2.96-2.87 (m, 5H), 2.78-2.76 (m, 2H), 2.47-2.43 (m, 2H), 1.75-1.73 (m, 4H), 1.71-1.53 (m, 4H), 1.04 (m, IH), 0.95 (m, IH), IR(KBr): 1668 cm'1
EXAMPLE 89
Preparation of (la, 5a, 6a)-N-[3-hexyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenyIacetamide (Compound No.89)
The compound was synthesized using the procedure described in Example 54 using 1-bromohexane instead of 2-cyanobenzyl bromide.
'HNMR (CDC13, 5-values): 7.58-7.56 (m, 2ArH), 7.36-7.26 (m, 3ArH), 6.31 (bs, IH), 3.14-2.86 (m, 5H), 2.33-2.25 (m, 4H), 1.61-1.22 (m, 18H), 0.86 (t, 3H), IR (DCM): 1653cm'1
EXAMPLE 90
Preparation of (la, 5a, 6a)-N-[3-(l,2,3,4-tetrahydronaphth-l-yl)-3-azabicyclo[3.1.0]-hex-6-yI]-2-hydroxy-2-cyclopenty 1-2-phenylacetamide (Compound No.90)
The compound was synthesized following the procedure of Example 46 using 1,2,3,4-tetrahydro-1-naphthylbromide instead of 1-bromoindan..pt: 66-71°C ,'HNMR (CDC13, 8-values): 7.62-7.03 (m, 9ArH), 6.37 (bs, 1H), 3.66 (bs, 1H), 3.18-2.72 (m, 9H), 2.08-1.29 (m, 13H), IR (KBr): 1657 cm'1
EXAMPLE 91
Preparation of (la, 5a, 6a)-N-[3-(2-chlorobenzyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.91)
The compound was synthesized following the procedure of Example 10, using 2-chlorobenzyl bromide instead of 3,5-dimethoxybenzyl bromide.
'HNMR (CDCb, 5-values^: 7.58-7.12 (m, 9ArH), 6.38 (s, 1H), 3.65 (s, 2H), 3.12-1.10 (m, 16H),IR(KBr): 1658 cm"'
EXAMPLE 92
Preparation of (la, 5a, 6a)-N-[3-(2-(2-methoxyphenyl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 92)
The compound was synthesized following the procedure of Example 10, using 2-methoxyphenethyl bromide instead of 3,5-dimethoxybenzylbromide.
'HNMR (CDC13, 5-values): 7.58-6.79 (m, 9ArH), 6.31 (bs, 1H), 3.77 (s, 3H), 3.16-2.35 (m, 10H), 1.65-1.41 (m, 10H), IR(KBr): 1659cm-'
EXAMPLE 93
Preparation of (la, 5a, 6a)-N-[3-(2-(4-fluorophenyl)ethyl]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 93)
The compound was synthesized following the procedure of Example 10, using 2-(4-fluorophenyl)ethyl bromide instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, S-values): 7.59-6.89 (m, 9ArH), 6.37 (bs, 1H), 3.15-2.33 (m, 11H), 1.64-1.18 (m, 1 OH), IR (DCM): 1654 cm"'
EXAMPLE 94
Preparation of (la, 5a, 6a)-N-[3-[l-(indan-5-yl)ethyl]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.94)
The compound was synthesized following the procedure of Example 10, using 5-(l-bromoethyl)indane instead of 3,5-dimethoxybenzylchloride.
1 HNMR (CDC13,8-values): 7.56-6.93 (m, 8ArH), 6.30 (bs, 1H), 3.27-2.76 (m, 11H),2.05-1.20(m, 15H)
EXAMPLE 95
Preparation of (la, 5a, 6a)-N-[3-[l-(naphth-l-yl)ethyl]-3-azabicyclo[3.1.0]-hex-6-yI]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.95)
The compound was synthesized following the procedure of Example 10, using 1-(1-bromoethyl)naphthalene instead of 3,5-dimethoxybenzyl chloride.
m.pt: 82-87°C, 'HNMR (CDC13) 8-values): 8.36-7.25 (m, 12ArH), 3.95-3.93 (q, 1H), 3.43-2.04 (m, 7H), 1.57-1.23 (m, 13H), IR(KBr): 1654cm'1
EXAMPLE 96
Preparation of (la, 5a, 6a)-N-[3-[l-(3,4-methylene dioxyphenyl) ethyl]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenyIacetamide (Compound No.96)
The compound was synthesized following the procedure of Example 10, using 1-(1-bromoethyl)3,4-methylene dioxyphenyl instead of 3,5-dimethoxybenzyl chloride.
m.pt: 53-56°C, 'HNMR (CDC13, 8-values): 7.62-6.37 (m, 8ArH), 5.94 (m, 2H), 3.30-2.39 (m, 7H), 1.65-1.23 (m, 13H), IR(KBr): 1655cm-'
EXAMPLE 97
Preparation of (la, 5a, 6a)-N-[3-[l-(l,2,3,4-tetrahydronaphth-6yl)ethyl]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.97)
The compound was synthesized following the procedure of Example 10, using 1-(1-bromoethyl)l,2,3,4-tetrahydronaphthalene instead of 3,5-dimethoxybenzyl chloride.
m.pt: 73-78°C, 'HNMR (CDC13, 6-values): 7.60-6.89 (m, 8ArH), 6.33 (s, 1H), 3.28-2.73 (m, 9H), 2.37 (q, 1H), 2.02-1.58 (m, 14H), 1.27-1.12 (m, 5H), IR(KBr): 1654.8 cm'1
EXAMPLE 98
Preparation of (la, 5a, 6a)-N-[3-[l-cis-(hex-3-enyl)]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No.98)
The compound was synthesized following the procedure of Example 10 using (la,5a,6ot)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and cis-3-hexen-l-methanesulphonate instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13, 8-values): 7.59-7.26 (m, 5ArH), 6.0 (bs, 1H), 5.38-5.26 (m, 2H), 3.15-2.93 (m, 2H), 2.83 (s, 1H), 2.37-2.32 (m, 9H), 2.13-2.11 (m, 2H), 2.04-2.01 (m, 2H), 1.45-1.25 (m, 2H), 0.97-0.92 (m, 3H), 0.58-0.52 (m, 5H), IR (DCM): 1652cm'1
EXAMPLE 99
Preparation of (la, 5a, 6a)-N-[3-[l-(trans hex-3-enyl)]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide (Compound No.99)
The compound was synthesized following the procedure of Example 10 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and trans-3-hexen-l-methane sulphonate instead of 3,5-dimethoxybenzyl chloride.
'HNMR(CDC13 8-values): 7.62-7.33 (m, 5ArH), 6.04 (bs, IH), 5.55-5.33 (m, 2H), 3.15-2.93 (m, 2H), 2.83 (s,' IH), 2.37-2.32 (m, 9H), 2.13-2.11 (m, 2H), 2.04-2.01 (m, 2H), 1.45-1.25 (m, 2H), 0.97-0.92 (m, 3H), 0.58-0.52 (m, 5H), IR (DCM): 1652cm'1
EXAMPLE 100
Preparation of (la, 5a, 6a)-N-[3-[l-(trans hex-3-enyl)]-3-azabicyclo[3.1.0] hex-6-yl ]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.100)
The compound was synthesized following the procedure of Example 10 using (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and trans-3-hexen-l-methanesulphonate instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13, 8-values): 7.59-7.23 (m, 5ArH), 6.59 (bs, IH), 5.45-5.30 (m, 2H), 3.11-3.08 (m, 2H), 2.39-2.36 (m, 3H), 3.11-3.08 (m, 2H), 2.86 (s, IH), 2.39-2.36 (m, 3H), 2.06-1.97 (m, 6H), 1.45-1.22 (m, 13H), 0.96-0.89 (m, 2H), IR(DCM): 1652cm'1
EXAMPLE 101
Preparation of (la, 5a, 6a)-N-[3-[l-(cis hex-3-enyl)]-3-azabicyclo[3.1.0] hex-6-yl 1-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.101)
The compound was synthesized following the procedure of Example 10 using cis-3-hexene-1-methanesulphonate instead of 3,5-dimethoxybenzyl chloride and (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide.
'HNMR (CDC13, 8-values): 7.59-7.23 (m, 5ArH), 6.58 (bs, IH), 5.38-5.23 (m, 2H), 3.10-3.07 (m, 2H), 2.8 (s, IH), 2.39-2.34 (m, 4H), 2.13-2.01 (m, 5H), 1.66-1.42 (m, 10H), 1.26-0.89 (m, 5H), IR (DCM): 1651cm'1
EXAMPLE 102
Preparation of (la, 5a, 6a)-N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenylacetamide (Compound No.102)
The compound was synthesized following the procedure of Example 10 using trans-hex-3-ene-1-methane sulphonate instead of 3,5-dimethoxybenzyl chloride.
'HNMR(CDC13, 8-values): 7.63-7.23 (m, lOArH), 6.11 (bs, IH), 3.56 (m, 2H), 3.41 (bs, IH), 3.14-3.10 (m, 2H), 2.93-2.90 (m, 2H), 2.30-2.04 (m, 2H), 1.59-1.42 (m, 3H), 1.42-1.37 (m, IH), 1.25 (s, 2H), 0.67-0.47 (m, 5H).
EXAMPLE 103
Preparation of (la, 5a, 6a)-N-[3-[l-(cis hex-3-enyl)]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.103)
The compound was synthesized following the procedure of Example 10 using cis-hex-3-ene-1-methanesulphonate instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13, 8-values): 7.58-7.27 (m, 5ArH), 6.34 (bs, 1H), 5.40-5.22 (m, 2H), 3.4-3.0 (m, 4H), 2.84 (m, 1H), 2.33 (m, 4H), 2.12-1.98 (4H), 1.7-1.2 (m,13H), IR(DCM): 1651cm'1
EXAMPLE 104
Preparation of (la, 5a, 6a)-N-[3-(2-naphthylmethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No. 104)
The compound was synthesized following the procedure of Example 53 using 2-(bromomethyl)naphthalene instead of 2-cyanobenzylbromide.
m.pt.: 70-72°C, 'HNMR (CDC13) 8-values): 7.79-7.72 (m, 3ArH), 7.63-7.56 (m, 3ArH), 7.44-7.23 (m, 6ArH), 6.38 (bs, 1H), 3.69 (s, 2H), 3.11-2.98 (m, 5H), 2.41-2.38 (m, 2H), 1.69-1.43 (m, 8H), 1.28-1.11 (m, 2H), IR (KBr): 1656cm'1
EXAMPLE 105
Preparation of (la, 5a, 6a)-N-[3-[(2-phenyl-l-methyl-2-oxo)ethyl]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.105)
The compound was synthesized following the procedure of Example 53 using 2-bromopropiophenone instead of 2-cyanobenzyl bromide.
m.pt.: 57-59°C,'HNMR (CDC13, 8-values): 8.04-8.01 (m, 2ArH), 7.60-7.22 (m, 8ArH), 6.39 (bs, 1H), 3.98 (q, 1H), 3.09-2.92 (m, 4H), 2.73-2.55 (m, 3H), 1.79-1.41 (m, 8H), 1.25-1.10 (m, 5H), IR(KBr): 1658cm'1
EXAMPLE 106
Preparation of (la, 5a, 6a)-N-[3-(2-(4-carbamoylphenyl) ethyl)-3-azabicycIo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.106)
The compound was synthesized following the procedure of Example 10, using 4-carbamoyl phenethylbromide instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13, S-values): 7.70-7.67 (d, 2ArH), 7.52-7.41 (m, 2ArH), 7.35 (m, 1H), 7.22-6.86 (m, 3H), 3.01-2.98 (m, 1H), 2.72-2.58 (m, 7H), 1.55-0.78 (m, 10H), IR (KBr): 1659, 1618cm'1
EXAMPLE 107
Preparation of (la, 5a, 6a)-N-[3-(2-(4-benzyloxycarbonylphenyl)ethyI)-3-azabicyclo[3.1.0]-hex-6-yI]-2-hydroxy-2-cycIopentyI-2-phenylacetamide (Compound No. 107)
The compound was synthesized following the procedure of Example 10 using benzyl-4-(2-bromoethylbenzoate instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13, 8-values): 7.96-7.93 (d, 2H), 7.55-7.51 (d, 2H), 7.44-7.19 (m, 10H), 6.39 (bs, 1H), 5.33 (s, 2H), 3.16-2.98 (m, 4H), 2.82-2.62 (m, 5H),2.40-2.32 (s, 2H), 1.82-0.84 (m,
10H),IR(DCM): 1718, 1659cm'
XAMPLE 108
Preparation of (la, 5a, 6a)-N-[3-[l-(2-methylpropyl)benzene]-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenyIacetamide (Compound No.108)
The compound was synthesized by following the procedure described in Example 10 using (l-bromo-2-methylpropyl)benzene instead of 3,5-dimethoxybenzylchloride.
m.pt: 143-145°C, 'HNMR (CDC13, 8-values): 7.58-7.08 (m, 8ArH), 6.35 (bs, 1H), 3.16-2.84 (m, 5H), 2.09-2.05 (m, 2H), 2.74-2.67 (m, 6H), 2.4 (m, 1H), 1.64-1.25 (m, 10H)
EXAMPLE 109
Preparation of (la, 5a, 6a)-N-[3-(2-phenyl-l-methyl-2-oxo)ethyI]-3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No.109)
The compound was synthesized following the procedure of Example 53, using (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and 2-bromopropiophenone instead of 2-cyanobenzylbromide.
m.pt: 79-81°C, 'HNMR (CDC13, 8-values): 8.04-8.02 (m, 2ArH), 7.58-7.25 (m, 8ArH), 6.60 (bs,lH), 3.98 (q, 1H), 3.08-3.04 (m, 1H), 2.94-2.90 (m, 1H), 2.73-2.56 (m, 5H), 1.68-1.64 (m, 1H), 1.59-1.10(m, 13H), 0.99 (m, lH),IR(KBr): 1674cm-1
EXAMPLE 110
Preparation of (la, 5a, 6a)-N-[3-hexyl-3-azabicycIo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound No. 110)
The compound was synthesized by following the procedure of Example 53 using (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide instead of (la, 5a, 6a)-N-(3-azabicyclo-[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide and 1-bromohexane instead of 2-cyanobenzyl bromide.
m.pt: 59-61°C, 'HNMR (CDC13, 8-values): 7.59-7.56 (m, 2ArH), 7.35-7.22 (m, 3ArH), 6.57 (bs,lH), 3.09-3.04 (m, 2H), 2.85-2.77 (m, 2H), 2.37-2.26 (m, 5H), 1.64-1.11 (m, 18H), 0.87-0.83 (m, 4H), IR (KBr): 1655cm"'
EXAMPLE 111
Preparation of (la, 5a, 6a)-N-[3-(2-(4-cyanophenyl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.Ill)
The compound was synthesized by following the procedure of Example 10, using 4-cyanophenyl ethyl bromide instead of 3,4-dimethoxybenzylchloride.
'HNMR (CDC13, S-values): 7.56 (m, 4H), 7.33-7.26 (m, 5H), 6.53 (bs,lH), 3.63 (s, 1H), 3.24 (m, 2H), 3.01 (m, 2H), 2.85-2.74 (m, 3H), 2.55 (m, 2H), 2.4 (m, 1H), 1.86-0.86 (m, 10H), IR (KBr): 1658cm'1 and 2228 cm'1
XAMPLE 112
Preparation of (la, 5a, 6a)-N-[3-(2-(4-sulphamoylphenyl)ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound 112)
The compound was synthesized by following the procedure of Example 10 using 4-sulphamoyl phenethylbromide instead of 3,5-dimethoxybenzyl chloride.
'HNMR (CDC13 5-values): 7.81-7.78 (m, 2H), 7.60-7.58 (m, 2H), 7.44-7.22 (m, 6H), 3.18-3.02 (m, 3H), 2.78-2.68 (m, 5H), 2.50 (bs, 2H), 2.4 (m, IH), 1.61-0.86 (m, 10H), IR (KBr): 1656cm"1
EXAMPLE 113
Preparation of (la, 5a, 6a)-N-[3-cycIohexylmethyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyI-2-phenylacetamide (Compound No.113)
The compound was synthesized by following the procedure of Example 10 using cyclohexylmethyl methane sulphonate instead of 3,5-dimethoxybenzylchloride.
'HNMR (CDC13, 8-values): 7.58-7.14 (m, 5H), 6.35 (s, IH), 3.38-2.88 (m, 5H), 2.25-1.78 (m, 4H), 1.7-1.1 (m, 20H), IR (DCM): 1645cm'1
EXAMPLE 114
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2,2-diphenylacetamide (Compound No. 114)
A solution of diphenylacetic acid (1 mmol) and (la, 5a, 6a)-3-benzyl-3-azabicyclo[3.1.0]-6-amino hexane (1.1 mmol) in 5 ml of DMF was cooled .to 0°C. HOBT (1.2 mmol) and NMM (1 mmol) were added to the reaction mixture and stirred for 30 min. at 0°C.EDC (Immol) was added to the reaction mixture and stirred for 1 hr. at 0°C and then at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh silicagel) eluting the compound with 50:50 EtOAc-hexane mixture to give a yellow solid.
m.pt: 169°C, 'HNMR (CDC13, 8-values): 7.37-7.18 (m, 15ArH), 5.57 (bs, IH), 4.83 (s, IH), 3.54 (s, 2H), 3.08-2.93 (m, 3H), 2.37-2.35 (d, 2H), 1.28-1.24 (m, 2H), IR (KBr): 1648cm-1
EXAMPLE 115
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-chloro-2-cycIohexyl-2-phenylacetamide (Compound No. 115)
A solution of (la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino[3.1.0] hexane (1 mmol) was dissolved in 5 ml of DCM and cooled to -20°C. A solution of 2-chloro-2-cyclohexyl-2-phenylacetylchloride (1.1 mmol) in DCM (5 ml) was added to the reaction mixture and the reaction mixture was stirred at the same temperature for half an hour. It was then warmed to
room temperature for 15 minutes. Triethylamine (2 mmol) was added after cooling the reaction mixture to -20°C. The reaction mixture was stirred at the same temperature for 30 minutes, warmed to room temperature and stirred at room temperature for 2 hours. The reaction mixture was poured into water and extracted with DCM. The organic layer was dried, concentrated under reduced pressure and the residue purified by column chromatography (100-200 mesh size, silicagel) eluting the compound with 15:85 EtOAc-hexane mixture.
'HNMR (CDC13, 5-values): 7.67-7.20 (m, 5ArH), 6.82 (s, IH), 3.53 (s, 2H), 3.10-3.02 (m, 3H), 2.38-2.31 (m, 2H), 1.73-0.87 (m, 13H), IR (KBr): 1674cm'1
EXAMPLE 116
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-cycIohexyl-2-phenylacetamide (Compound No. 116)
Step-a: Synthesis of cc-cyclohexylphenylacetonitrile.
The compound was synthesized following the procedure described in Organic Synthesis Coll. Vol. 3 pg 220.
Step-b: Synthesis of a-cyclohexylphenylacetic acid.
To a mixture of 7.5 ml each of cone, sulphuric acid, acetic acid and water, the compound of
Step-a (10 mmol) was added and the reaction mixture was refluxed for 12 hours. The
reaction mixture was poured into ice and extracted with dichloromethane. The organic layer
was separated and concentrated under reduced pressure and purified by column
chromatography.
Step-c: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-phenylacetamide.
The compound was synthesized following the procedure of Example 1 using a-cyclohexylphenylacetic acid instead of 2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenylacetic acid and (la, 5a, 6a)-N-[3-benzyl-6-amino-3-azabicyclo [3.1.0] hexane (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)]-6-amino-3-azabicyclo[3.1.0]-hexane hydrochloride.
'HNMR (CDC13): 7.34-7.16 (m, lOArH), 5.47 (bs, IH), 3.60 (s, 2H), 3.08-2.98 (m, 3H), 2.76 (dm, 2H), 2.35 (m, 2H), 1.43-0.91 (m, 11H), IR(KBr): 1646cm"1
EXAMPLE 117
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-phenylacetamide (Compound No.117)
(la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino[3.1.0]-hexane (1 mmol) was dissolved in DMF (10 ml) and to it 2-hydroxy-2-phenylacetylchloride (1.2 mmol) was added followed by the addition of potassium carbonate (2 mmol) and potassium iodide (2 mmol). The reaction
ixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried and the residue obtained after removal of solvents was purified by column chromatography (100-200 mesh size silicagel) eluting the compound with DCM.
m.pt. 81°C, 'HNMR (CDC13, 8-values): 7.41-7.21 (m, lOArH), 6.69 (bs, 1H), 5.34 (s, 1H), 3.59 (s,2H), 3.15-3.11 (m, 3H), 2.45-2.41 (m, 2H), 1.62-1.55 (m, 2H), IR(KBr): 1666cm'1
EXAMPLE 118
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyI-2-phenylacetamide (Compound No. 118)
Step-a: Synthesis of a-cyclopenrylphenylacetonitrile.
The compound was synthesized following the procedure described in Organic Synthesis Coll.
Vol. 3 pg. 220, using cyclopentylbromide instead of cyclohexylbromide.
Step-b: Synthesis of ct-cyclopentylphenylacetic acid.
The compound was synthesized following the procedure described of Example-116, step-b,
using a-cyclopentylphenylacetonitrile instead of a-cyclohexylphenylacetonitrile.
Step-c: Synthesis of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-
cyc lopenty 1-2-pheny lacetamide
The compound was synthesized following the procedure of Example-1, using a-
cyclopentyIphenylacetic acid instead of 2-hydroxy-2-cyclopentyl-2-(4-methoxy) phenylacetic
acid and (la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino[3.1.0]hexane instead of (la, 5a, 6a)-
N-[3-(4-methyl-3-pentenyl)]-6-amino-3-azabicyclo[3.1.0]hexanehydrochloride.
'HNMR (CDC13, 5-value): 7.34-7.16 (m, lOArH), 5.42 (s, 1H), 3.64 (s, 2H), 3.08-2.86 (m, 4H), 2.35 (m, 2H), 1.68-1.19 (m, 8H), 0.88 (m, 2H), IR (DCM): 1644cm'1
EXAMPLE 119
Preparation of (la, 5a, 6a)-N-[3-benzyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-phenylpropionamide (Compound No. 119)
The compound was synthesized following the procedure of Example-1 using 2-hydroxy-2-phenyl propionic acid instead of 2-hydroxy-2-cyclopentyl-2-(4-methoxy)phenyl acetic acid and (la, 5a, 6a)-3-benzyl-3-azabicyclo-6-amino[3.1.0]hexane instead of (la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)]-6-amino-3-azabicyclo[3.1.0]-hexane hydrochloride.
'HNMR (CDC13, 8-value):7.53-7.18 (m, lOArH), 6.35 (bs, 1H), 3.53 (s, 2H), 3.07-3.04 (m, 3H), 2.38-2.33 (m, 2H), 1.78 (s, 3H), 0.970-0.85 (m, 2H), IR (DCM): 1659cm'1
EXAMPLE 120
Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(l-phenyl ethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide (Compound No.120)
Step-a: Preparation of N-(l-tert-Butoxycarbonyl )(la, 5a, 6a)-N-[3-
azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
To a cold solution of Igm (Immol) of (la, 5a, 6a)-N- [3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide in DCM (50 ml) were added 0.9 ml (2mmol) of triethylamine and 0.6 ml, 1 .2 mmol of Ditert-butyl dicarbonate diluted with DCM (2 ml) at 0°C. The reaction mixture was stirred at 0°C for 20 minutes and then at room temperature for 2 hours. The reaction mixture was poured into water, and the organic layer was separated, dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The crude compound was purified by column chromatography and the desired product eluted with 30:70 EtOAC-Hexane.
m.pt: 69-75°C, 'HNMR (CDC13, 5-value): 7.23-7.50 (m, 5ArH), 6.59 (s, 1H), 3.67-3.64 (m, 2H), 3.35-3.31 (m, 2H), 2.96 (m, 1H), 2.94 (m, 1H), 1.66-1.45 (m, 8H), 1.40 (s, 9H), 1.26 -1.25(m,
Step-b: Preparation of N-(l-tert-ButyloxycarbonyI)-(la, 5a, 6a)-N-[3-
azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyl-2-trimethylslilyloxy-2-phenylacetamide
To a stirred solution of compound in step 120-a (960mg, 1 mmol) and imidazole (604 mg, 3.7 mmol) in DMF (20 mg), was added trimethylsilylchloride (0.8 ml, 2.7 mmol) at room temperature and the reaction mixture was stirred for 18 hours. The reaction mixture was poured into water and extracted with diethylether. The organic layer was washed with rfeO, brine, and dried over anhydrous Na2SC>4. The evaporation of solvent gave the crude product which was purified by silicagel column chromatography. The desired product was eluted with 10:90 EtOAc -hexane mixture.
'HNMR (CDC13, 8-value):7.63-7.53 (m, 5ArH), 7.30 (s, 1H), 4.02-3.98 (d, 2H), 3.66 (s, 2H), 3.24-3. 13 (m, 1H), 2.74 (s, 1H), 2.11-1.84 (m, 8H), 1.69 (s,9H), 1.38 (m, 1H), 1.15(m, 1H), 0.2 1 4 (s, 9H).
Step-c: Preparation of N-methyl-N-(l-tert-butoxycarbonyl) (la, 5a, 6a)-N-[3-
azabicyc!o[3.1.0]-hex-6-yl]-2-hydroxy-2-cycIopentyl-2-phenyIacetamide
To a stirred solution of compound synthesized in step-120b (825 mg, 1 mmol) in dry THF (15 ml), were sequentially added sodium hydride (556 ml, 152 mg, 1.8 mmol), and tetrabutyl ammonium iodide (50 mg, 0.07 mmol) at 0°C. After 10 minutes, iodomethane was added. The mixture was allowed to warm to room temperature and stirred for 19 hours. The reaction mixture was quenched with saturated NHjCl solution and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SC>4 and
concentrated. The residue was purified by silica gel column chromatography and the desired product eluted with 8:92 EtOAc-Hexane mixture.
IR: 1699.1 cm'1, 1651.9cm'1 'HNMR (CDC13, 5-value): 7.29-7.23 (m, 5 ArH), 3.7 (bs, 2H), 3.40 (bs, 2H), 2.76 (bs, 2H), 2.44 (s, 3H), 1.80-1.51 (m, 8H), 1.43 (s, 9H), 1.25 (m, 1H), 1.22 (m, 1H), 0.19(s, 3H)
Step-d: Preparation of N-methyl (la, 5a, 6a)-N-[3-azabicyclo[3.1.0]-hex-6-yl]-2-
cycIopentyl-2-hydroxy-2-phenyIacetamide hydrochloride.
The compound synthesized in step c (330 m, Immol) was dissolved in 10% HCl-MeOH (8 ml) and the mixture was stirred for 17 hours at room temperature. The solvent was evaporated to obtain the crude compound which was used without purification.
IR: 1631.30 cm'1, 'HNMR (CDC13, 8-value): 7.40-7.13 (m, 5ArH), 3.60 (bs, 2H), 3.42 (bs, 2H), 2.96 (bs, 2H), 2.75 (s, 3H), 2.00-1.55 (m, 8H), 1.32-1.25 (m, 2H).
Step-e: Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(l-phenyl ethyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide
To a solution of compound of step-120d (230 mg, 1 mmol) in CH3CN (25 ml) were added potassium carbonate (226 mg, 3 mmol), 1-bromo-l-phenylethane (160 mg, 1.5 mmol) and potassium iodide (170 mg, 1.5 mmol) at room temperature. The reaction mixture was refluxed for 8 hours. The reaction mixture was extracted with EtOAc. The combined organic extract was dried over anhy. Na2SO4 and concentrated. The crude compound was purified by silica gel (100-200 mesh) column chromatography and the desired product was eluted with 20:80 EtOAc/Hexane mixture.
IR= 1628cm-1, 'HNMR (CDC13, 8-value): 7.41-7.19 (m, lOArH), 5.27 (s, 1H), 3.20-3.18 (m, 2H), 3.02-2.99 (m, 2H), 2.74-2.70 (m, 1H), 2.68 (s, 3H), 2.25 (m, 1H), 2.21 (m, 1H), 1.18-1.38(m, 8H), 1.29(s,3H), 1.26(m, 1H), 1.25(s,
EXAMPLE 121
Preparation of N-methyl-N-(lcc, 5a, 6a)-N-[3-(3,4-methylenedioxyphenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-cycIopenryl-2-hydroxy-2-phenyIacetamide (Compound No.121)
This compound was synthesized following the same procedure as for Example 120, using 3,4-methylenedioxyphenyl ethyl bromide instead of 1-bromo-l-phenyl ethane. The desired product was eluted with 50:50 EtoAc-Hexane mixture.
IR (DCM): 1621.2cm'1, 'HNMR (CDCl3-8-values): 7.39-7.21 (m, 5ArH), 6.74-6.60 (m, 3Ar-H), 5.92 (s, 2H), 5.17 (s, 1H), 3.14-3.01 (m, 4H), 2.71 (s, 3H), 2.60-2.58 (m, 4H), 2.33 (m, 2H), 1.79-1.38 (m, 10H).
EXAMPLE 122
Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(l-benzyl)-3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide (Compound No. 122)
This compound was synthesized following the same method as for Example 120e, using benzyl bromide instead of 1-bromo-l-phenyl ethane. The desired product eluted with 50:50 EtoAc/Hexane mixture.
'HNMR (CDC13, 8-value): 7.40-7.23 (m, lOArH), 5.19 (s, 1H), 3.54 (s, 2H), 3.03 (m, 4H), 2.70 (s, 3H), 2.35 (m, 2H), 1.79-1.44 (m, 8H), 1.42 (m, 1H), 1.25 (m, 1H), IR= 1627.8 cm'1
EXAMPLE 123
Preparation of N-methyl (la, 5a, 6a)-N-[3-(3,4-methylenedioxyphenethyl-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide (Compound No. 123)
Step-a: Preparation of N-(l-tert-butoxycarbonyl) (la, 5a, 6a)-N-[3-azabicyclo
[3.1.0]-hex-6-yl]-2-hydroxy-cyclohexyl-2-phenylacetamide
This compound was synthesized following the same method as for Example 120, step a, by using (la, 5a, 6a)-N-[3-(3-azabicyclo[3.1.0]-hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide instead of (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-hydroxy -2-cyclopentyl-phenylacetamide.
m.pt: 93-97°C, 'HNMR (CDC13, 8-values): 7.59-7.23 (m, 5ArH), 6.78 (s, 1H), 3.67-3.61 (m, 2H), 3.35-3.32 (m, 2H), 2.61 (s, 1H), 2.41-2.37 (m, 2H), 1.77-1.44 (m, 10H), 1.40 (s, 9H), 1.11 (m, 1H), 0.85 (m, 1H), IR : 1698.8 cm'1 and 1676cm'1
Step-b: Preparation of N-(l-tert-butyloxycarbonyl) (la, 5a, 6a)-N-[3-azabicyclo
[3.1.0]-hex-6-yl]-2-cyclohexyl-2-trimethylsilyloxy-2-phenylacetamide
This compound was synthesized following the same procedure as for Example 120, step-b, usingN-(l-tert-butyloxycarbonyl) (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenyl acetamide instead of N-(t-tert-butyloxycarbonyl (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclopenyl-2-hydroxy-2-phenylacetamide.
m.pt. : 62-66°C, 'HNMR (CDC13, 6-value): 7.26-7.14 (m, 5ArH), 3.74-3.64 (m, 2H), 3.40 (bs, 2H), 2.37 (s, 3H), 2.30 (bs, 2H), 1.71-1.53 (m, 10H), 1.42 (s, 3H), 1.33-1.21 (m, 2H), 0.19 (s, 9H), IR :1701.15cm"' 1652.3cm'1
Step-c: Preparation of N-methyl-N-(l-tert-butyloxy carbonyl) la, 5a, 6a)-N-[3-
azabicyclo [3.1.0]hex-6-yl]-2-cyclohexyl-2-trimethylsilyloxy-2-phenylacetamide.
This compound was synthesized following the same procedure as for Example 120, step-c, using N-(l-tert-butyloxy carbonyl ) ( la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-cyclohexyl-2-trimethyl-silyloxy-2-phenylacetamide instead of N-(l-tert-butyloxy carbonyl )
(la, 5a, 6a)-N-[3-azabicyclo [3.1.0]hex-6-yl]-2-cyclohexyl-2-trimethylsilyloxy-2-phenylacetamide. The desired product eluted with 25:75 EtoAc/hexane mixture.
m.pt.: 62-66°C, 'HNMR (CDCl3-8-values): 7.26-7.14 (m, 5ArH), 3.74-3.64 (m, 2H), 3.40 (bs, 2H), 2.37 (s,3H), 2.30 (bs,2H), 1.71-1.53 (m, 10H), 1.42 (s,3H), 1.33-1.21 (m, 2H), 0.19 (s, 9H), IR(KBr): 1701.5 cm'1 and 1652.3 cm'1
Step-d: Preparation of N-methyl(la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yI]-2-
cyclohexyl-2-hydroxy-2-phenylacetamide hydrochloride
This compound was synthesized following the same procedure as for Example 120, Step-d, by using N-methyl-N-( 1-tert-butyloxy carbonyl) (la, 5a, 6a)-N-[3-azabicyclo [3.1.0]-hex-6-yl]-2-cyclohexyl-2-trimethylsilyloxy-2-phenylacetamide.
'HNMR (CDC13, 8-value): 7.42-7.22 (m, 5ArH), 5.30 (s, 1H), 3.73-3.00 (m, 6H), 2.81 (s, 3H), 1.82-1.38 (m, 10H), 1.32-1.25 (m, 2H), IR: 1627.10cm'1
Step e: Preparation of N-methyl(la, 5a, 6a)-N-[3-(3,4-methylenedioxyphenethyl-
3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide
This compound was synthesized following the same procedure as for Example 120, using compound synthesized in step-123d and 3,4-methylenedioxyphenylethylbromide. The crude compound was purified by silicagel (100-200) column chromatography and the desired product was eluted with 40:60 EtoAc/Hexane.
'HNMR (CDC13, 8-value): 7.41-7.21 (m, 5ArH), 6.74-6.61 (m, 3 ArH), 5.92 (s, 2H), 4.80 (s, 1H), 3.21-3.18 (m, 1H), 3.06-2.95 (m, 2H), 2.75 (s, 3H), 2.65-2.49 (m, 5H), 2.37-2.32 (t, 2H), 1.80-0.88 (m, 12H), IR (KBr): 1622.2 cm"1
EXAMPLE 124
Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yI]-2-cyclohexyl-2-hydroxy-2-phenylacetamide (Compound No.124)
This compound was synthesized following the same procedure as for Example 123, using 5-bromo-2-methyl-2-pentene instead of 3,4-methylenedioxyphenylethylbromide.
Eluent = 40% EtoAc/Hexane
'HNMR (CDC13, 8-value): 7.43-7.21 (m, 5ArH), 5.12-5.07 (t, 1H), 4.87 (s, 1H), 3.39-3.36 (m, 1H), 3.18-2.98 (m, 2H), 2.75 (s, 3H), 2.50 (bs, 1H), 2.38-2.27 (m, 3H), 2.12-2.05 (m, 2H), 1.69-1.25 (m, 14H), 1.11 (s, 6H), IR: 1627.1 cm"1
EXAMPLE 125
Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-cycIopentyl-2-hydroxy-2-phenylacetamide (Compound No.125)
The compound was synthesized following the same procedure as for Example 120, using 5-bromo-2-methyl-2-pentene instead of 1-bromo-l-phenyl ethane.
'HNMR (CDC13, S-value): 7.40-7.21 (m, 5ArH), 5.21 (s, 1H), 5.09-5.05 (t, 1H), 3.12-3.09 (m, 2H), 2.95 (s, 1H), 2.71 (s, 3H), 2.37-2.32 (m, 3H), 2.09-2.07 (m, 2H), 1.68 (s, 6H), 1.65-1.51 (m, 8H), 1.48-1.41 ( m, 2H), 1.25 (m, 2H), IR: 1632.8cm'1, 1651.9cm'1
EXAMPLE 126
Preparation of N-methyl-N-(la, 5a, 6a)-N-[3-(4-methyI-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopenryl-2-hydroxy-2-phenyIacetamide L(+) Tartarate salt (Compound No.126)
To a solution of compound synthesized in Example 125 (485 mg, Immol) in 8 ml of EtOH was added L (+) tartaric acid (184 mg, Immol) and the reaction mixture heated at 60°C for 1 hr. After 1 hour the reaction mixture was concentrated to give a solid compound.
mpt.: 71-75°C, IR (KBr): 1735cm'1 and 1625.7cm'1
HPLC: 98.60%
Biological Activity
Radioligand Binding Assays: The affinity of test compounds for M2 and Ms muscarinic
receptor subtypes was determined by [3H]-N-methylscopolamine binding studies using rat
heart and submandibular gland respectively as described by Moriya et al., (Life ScL
1999,64(25):2351-2358) with minor modifications.
Membrane preparation: Submandibular glands and heart were isolated and placed in ice
cold homogenizing buffer (HEPES 20mM, lOmM EDTA, pH 7.4) immediately after
sacrifice. The tissues were homogenized in 10 volumes of homogenizing buffer and the
homogenate was filtered through two layers of wet gauze and filtrate was centrifuged at 500g
for lOmin. The supernatant was subsequently centrifuged at 40,000g for 20 min. The pellet
thus obtained was resuspended in same volume of assay buffer (HEPES 20 mM, EDTA
5mM, pH 7.4) and were stored at -70°C until the time of assay.
Ligand binding assay: The compounds were dissolved and diluted in DMSO. The
membrane homogenates (150-250 ng protein) were incubated in 250 ul of assay buffer
(HEPES 20 mM, pH 7.4) at 24-25°C for 3h. Non-specific binding was determined in the presence of 1 uM atropine. The incubation was terminated by vacuum filtration over GF/B fiber filters (Wallac). The filters were then washed with ice cold 50mM Tris HC1 buffer (pH 7.4). The filter mats were dried and bound radioactivity retained on filters was counted. The IC5Q & Kd were estimated by using the non-linear curve fitting program using G Pad Prism
software. The value of inhibition constant Ki was calculated from competitive binding studies by using Cheng & Prusoff equation (Biochem Pharmacol, 1973,22: 3099-3108), Ki = IC5Q
/(1+L/Kd), where L is the concentration of [3H]NMS used in the particular experiment.
Functional Experiments using isolated rat bladder: Methodology:
Animals were euthanized by overdose of urethane and whole bladder was isolated and
removed rapidly and placed in ice cold Tyrode buffer with the following composition
(mMol/L) NaCl 137; KC1 2.7; CaCl2 1.8; MgCl2 0.1; NaHCO3 11.9; NaH2PO4 0.4; Glucose
5.55 and continuously gassed with 95% O2 and 5 % CO2.
The bladder was cut into longitudinal strips (3mm wide and 5-6 mm long) and mounted in 10
ml organ baths at 30° C, with one end connected to the base of the tissue holder and the other
end connected to a polygraph through a force displacement transducer. Each tissue was
maintained at a constant basal tension of 2 g and allowed to equilibrate for 1 hour during
which the PSS was changed every 15 min. At the end of equilibration period the stabilization
of the tissue contractile response was assessed with lumol/L of Carbachol consecutively for
2-3 times. Subsequently a cumulative concentration response curve to carbachol (10"9 mol/L
to 3 X 10"5 mol/L) was obtained. After several washes, once the baseline was achieved,
cumulative concentration response curve was obtained in presence of NCE (NCE added 20
min. prior to the second CRC).
The contractile results were expressed as % of control E max. ED50 values were calculated
by fitting a non-linear regression curve (Graph Pad Prism). PKB values were calculated by
the formula pKB = - log [ (molar concentration of antagonist/ (dose ratio-1))]
where,
dose ratio = ED50 in the presence of antagonist/ED50 in the absence of antagonist.
The results of In-Vitro tests are listed in Table I.Table-I

(Table Removed
)While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

WE CLAIM:
1. A 3,6 disubstituted azabicyclo hexane compounds as muscarinic receptor antagonists having the structure of Formula I:
(formula removed)
wherein
Ar represents an aryl wherein the aryl is unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C1-C4), trifluoromethyl, cyano, hydroxy, nitro, halogen (e.g. F, Cl, Br or I), lower alkoxy (C1-C4), amino or lower alkylamino(C1-C4);
R1 represents a hydrogen, hydroxy, halogen (e.g. F, C1, Br, I) or aryl;
R2 represents alkyl, C3-C7 cycloalkyl ring, C3-C7 cycloalkenyl 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 hetero aryl 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; W represents (CH2)P, where p represents 0;
X represents no atom;
Y represents a bond  m represents 0; R3 represents hydrogen or lower alkyl (C1-C4); and
R4 represents C1-C15 saturated or unsaturated aliphatic hydrocarbon (straight chain or branched) in which any 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen (e.g. F, Cl, Br, I), carboxylic acid, carboxylic acid ester, aryl, aryloxy, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur with option that any 1 to 5 hydrogen atoms on the ring in said aryl, aryloxy, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkenyl may be substituted with lower(C1-C4)alkyl, trifluoromethyl, halogen (e.g. F, Cl, Br, I), cyano, nitro, hydroxy, lower (C1-C4) alkoxy, amino, lower (C1-C4) alkylamino, sulphonylamino, amide, carboxylic acid, carboxylic acid ester or benzyl ester.

2. The compound as claimed in claim 1 having the structure of Formula IV, wherein Ar, R1, R3
and R4 are as defined for Formula I and r is 1 to 4.
(formula removed)
3. The compound as claimed in claim 1 having the structure of Formula V wherein Ar, R1,R3
and R4 are as defined for Formula I and s is 1 to 3.
(formula removed)
4. The compound as claimed in claim 1 having the structure of Formula VI wherein R3 and R4
are as defined for Formula I and s is 1 to 3.
(formula removed)
5. A compound as claimed in claim 1, selected from the group consisting of:
(1α,5α,6α)-2-cyclopentyl-2-hydroxy-2-(4-methoxyphenyl)-N- [3 -(2-methylprop-1 -en-1 -yl)-3 -azabicyclo[3.1,0]hex-6-yl]acetamide
(1α,5α,6α)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(5-nitro-2-furylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(hex-2-yl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(l ,4-benzodioxan-6-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3,4,5-trimethoxyphenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[3-(3,4-methylenedioxyphen-5-yl)propyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide

(1α,5α,6α)-N-[3-(3,4,5-trimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3,5-dimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3,4-dimethoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-trifluoromethylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(5-methyl-2-furylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2 -phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-methylphenoxy)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-chlorophenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-phenylpropyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-hydroxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l -phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-t-butylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-methylquinolinyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2- cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-nitro-4-methoxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-nitro-4-hydroxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(3 -aminobenzyl)-3-azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(6-aminopyridin-2-yl-methyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-phenoxyethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide

(1α,5α,6α)-N-[3-(3-cyclohexyloxypropyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-pyrrolin-2-ylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[(l ,4-benzodioxan-6-yl)-methyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3,4-methylendioxyphen-5-yl)ethyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[2-(3,4-methylenedioxyphenyl)ethyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-hydroxy-3-methoxybenzyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-hydroxy-4-methoxybenzyl]-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-phenylcarboethoxyethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(2-hydroxyphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(4-methylphenyl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(phenylmethylpyridine)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(4-pyridylmethyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l-indanyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(3-methylbenzyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2,4,6-trimethylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3,4-dimethoxyphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3-(2-(3,4-dimethylphenyl)ethyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-butyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide

(1α,5α,6α)-N-[3-(4-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2,3,4,5,6-pentafluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-cyanobenzyl)-3-azabicyclo-[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(pyrid-3-ylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-bromo-2-thienylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1 a,5a,6oc)-N- [3 - [ 1 -(phenyl)ethyl]-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-nitrobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-methoxycarbonyl]benzyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(diphenylmethyl)-3-azabicyclo [3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-carboxybenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-aminobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-carboethoxypropyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-acetylphenyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-methoxycarbonyl)phenyl)ethyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(3 -cyanobenzyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(2-cyanobenzyl)-3 -azabicyclo[3.1.0]hex-6-yl] -2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-cyanobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l -methylbutyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(4-hydroxymethylphenethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(3 -Fluoro-4-aminobenzyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide

(1α,5α,6α)-N- [3 -(1 -(3,4-dimethylphenyl)ethyl)-3-azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3 -methylphenoxy)ethyl)-3 -azabicyclo [3.1.0] hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(3-(3-methylphenoxy)propyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(2-methylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[(l,3-dioxolan-2-yl)-methyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[(l -carboxy)ethyl] -3 -azabicyclo [3.1.0] hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2,2-diphenylacetamide
(1α,5α,6α)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclooctyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N- [3-( 1 -phenylethyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l-phenylethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclobutyl-2-phenylacetamide
(1α,5α,6α)-N- [3 - [(2 -phenylcarboxy)ethyl] -3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cycloheptyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3-indoyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(naphth-2-yl-methyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -(2-(indoyl-3 -yl)ethyl)-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -hexyl-3 -azabicyclo[3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l,2,3,4-tetrahydronaphth-l-yl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-chlorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(2-methoxyphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-fluorophenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(indan-5-yl)ethyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide

(1α,5α,6α)-N-[3-(l-(naphth-l-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(l-(3,4-methylenedioxyphen-5-yl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(l,2,3,4-tetrahydronaphth-6-yl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 - [ 1 -cis-(hex-3 -enyl)] -3 -azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopropyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(trans-hex-3-enyl)]-3-azabicyclo[3.1.0] hex-6-yl ]-2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3 - [ 1 -(cis-hex-3 -enyl)]-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3 - [ 1 -(trans-hex-3 -enyl)] -3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(cis-hex-3-enyl)]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-naphthylmethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[(2-phenyl-l-methyl-2-oxo)ethyl]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-carbamoylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(4-benzyloxycarbonylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-[l-(2-methylpropyl)benzene]-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N- [3 - [(2-phenyl-1 -methyl-2-oxo)ethyl]-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N- [3 -hexyl-3 -azabicyclo [3.1.0]hex-6-yl] -2-hydroxy-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3-cyanophenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-(2-(3-sulphamoylphenyl)ethyl)-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-cyclohexylmethyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2,2-diphenylacetamide
(1α,5α,6α)-N- [3 -benzyl-3 -azabicyclo [3.1.0]hex-6-yl] -2-chloro-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-cyclohexyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-phenylacetamide

(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-cyclopentyl-2-phenylacetamide
(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hex-6-yl]-2-hydroxy-2-phenyl propionamide
N-methyl (1α,5α,6α)-N-[3-(l-phenyl-ethyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyl-2-
hydroxy-2-phenylacetamide
N-methyl (1α,5α,6α)-N-[3-(2-(3,4-methylenedioxyphen-5-ylethyl))-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide
N-methyl (1α,5α,6α)-N- [3-( 1 -benzyl)-3 -azabicyclo [3.1.0]-hex-6-yl] -2-cyclopentyl-2-hydroxy-2-phenylacetamide,
N-methyl-(1α,5α,6α)-N-[3-(2-(3,4-methylenedioxyphen-5-ylethyl))-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide,
N-methyl-N-(1α,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclohexyl-2-hydroxy-2-phenylacetamide,
N-methyl-N-(1α,5α,6α)-N-[3-(4-methyl-3-pentenyl)-3-azabicyclo[3.1.0]-hex-6-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide' and
N-methyl-N-(1α,5α,6α)-N- [3 -(4-methyl-3 -pentenyl)-3 -azabicyclo [3.1.0] -hex-6-yl] -2-cyclohexyl-2-hydroxy-2-phenylacetamide L (+)tartarate salt.
6. A process of preparing a compound of Formula I as claimed in claim 1,
(formula removed)
wherein Ar, R1 R2, W, X ,Y, m, R3 and R4 are the same as defined earlier, comprising
(a) condensing a compound of Formula VIII with a compound of Formula VII
(formula removed)
wherein Ar, R1, R2, W, X, Y and R3 have the same meanings as defined earlier for Formula I, and P is a protecting group for an amino group selected from the group consisting of benzyl and t-butyloxy carbonyl groups, to give a protected compound of Formula IX in the presence of a condensing agent which is selected from the group consisting of l-(3-dimethylaminopropyl)-3 -ethyl carbodiimide hydrochloride (EDC) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) in a solvent selected from the group consisting of N,N-

dimethylformamide, dimethylsulfoxide, toluene and xylene at temperature ranging from 0-140°C;
(formula removed)
(b) deprotecting the compound of Formula IX in the presence of a deprotecting agent
selected from the group consisting of palladium on carbon trifluoroacetic acid (TFA)
and hydrochloric acid to give an unprotected intermediate of Formula X in a organic
solvent selected from the group consisting of methanol, ethanol, tetrahydrofuran and
acetonitrile wherein Ar, R1, R2, W, X, Y, m and R3 as defined earlier, and
(formula removed)

(c) N-alkylating or benzylating the intermediate of Formula X with a alkylating or
benzylating agent L-R4 wherein L is any leaving group selected from the group
consisting of halogen, O-methyl and O-tosyl groups and R4 is as defined earlier to
give a compound of Formula I in a suitable organic solvent selected from the group
consisting of N,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran and
acetonitrile wherein Ar, R1, R2, W, X, Y, m, R3 and R4 are as defined earlier.