US2011301140A1PendingUtilityA1
Pyridine Carboxamide orexin Receptor Antagonists
Est. expiryAug 9, 2027(~1.1 yrs left)· nominal 20-yr term from priority
Inventors:Jeffrey M. BergmanPaul J. ColemanMark E. FraleySwati P. MercerThomas S. RegerAnthony J. RoeckerJustin T. Steen
A61P 43/00A61P 37/08A61P 3/10A61P 9/10A61P 9/04A61P 9/12A61P 9/00A61P 25/00A61P 25/04A61P 25/30A61P 25/20A61P 25/24A61P 3/04A61P 25/22A61P 35/00A61P 25/06A61P 25/16C07D 401/14C07D 213/82A61P 13/12A61P 15/00A61P 15/10C07D 401/04A61P 13/08A61P 1/04A61P 1/14A61P 1/08A61K 31/4439A61P 19/10A61P 11/06A61K 31/444A61K 31/4427A61P 13/02A61P 11/14
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Claims
Abstract
The present invention is directed to pyridyl carboxamide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
Claims
exact text as granted — not AI-modified1 . A compound of the formula I:
wherein:
A 1 is selected from the group consisting of phenyl, naphthyl and heteroaryl;
A 2 is selected from the group consisting of phenyl, naphthyl and heteroaryl;
A 3 is selected from the group consisting of phenyl, naphthyl, C 3-6 cycloalkyl, and heterocycle, with the provisio that if A 1 is heteroaryl and A 2 is heteroaryl, then A 3 is other then phenyl or napthyl;
R 1a , R 1b and R 1c may be absent if the valency of A 1 does not permit such substitution and are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) —(C═O) m O n —C 1-6 alkyl, where m is 0 or 1, n is 0 or 1 (wherein if m is 0 or n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(5) —(C═O) m —O n —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,
(10) —(C═O) m —NR 10 R 11 , wherein R 10 and R 11 are independently selected from the group consisting of:
(a) hydrogen,
(b) C 1-6 alkyl, which is unsubstituted or substituted with R 13 ,
(c) C 3-6 alkenyl, which is unsubstituted or substituted with R 13 ,
(d) C 3-6 alkynyl, which is unsubstituted or substituted with R 13 ,
(e) C 3-6 cycloalkyl which is unsubstituted or substituted with R 13 ,
(f) phenyl, which is unsubstituted or substituted with R 13 , and
(g) heterocycle, which is unsubstituted or substituted with R 13 ,
(11) —S(O) 2 —NR 10 R 11 ,
(12) —S(O) q —R 12 , where q is 0, 1 or 2 and where R 12 is selected from the definitions of R 10 and R 11 ,
(13) —CO 2 H,
(14) —CN, and
(15) —NO 2 ;
R 2a , R 2b and R 2c may be absent if the valency of A 2 does not permit such substitution and are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) —(C═O) m —O n —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(5) —(C═O) m —O n —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,
(10) —(C═O) m —NR 10 R 11 ,
(11) —S(O) 2 —NR 10 R 11 ,
(12) —S(O) q —R 12 ,
(13) —CO 2 H,
(14) —CN, and
(15) —NO 2 ;
R 3a , R 3b and R 3c may be absent if the valency of A 3 does not permit such substitution and are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) —(C═O) m —O n —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(5) —(C═O) m —O n —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R 13 ,
(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,
(10) —(C═O) m —NR 10 R 11 ,
(11) —S(O) 2 —NR 10 R 11 ,
(12) —S(O) q —R 12 ,
(13) —CO 2 H,
(14) —CN, and
(15) —NO 2 ;
with the proviso that if A 3 is pyridyl, at least one of R 3a , R 3b and R 3c is other than hydrogen;
R 4 and R 5 are independently selected from hydrogen and C 1-6 alkyl, which is unsubstituted or substituted with one or more substituents selected from R 13 , or R 4 and R 5 may be joined together to form a C 3-6 cycloalkyl with the carbon atom to which they are attached, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 13 ;
R 6 is hydrogen, C 1-6 alkyl or C 3-6 cycloalkyl, which is unsubstituted or substituted with one or more substituents selected from R 13 ;
R 13 is selected from the group consisting of:
(1) halogen,
(2) hydroxyl,
(3) —(C═O) m —O n —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 14 ,
(4) —O n —(C 1-3 )perfluoroalkyl,
(5) —(C═O) m —O n —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 14 ,
(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 14 ,
(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 14 ,
(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R 14 ,
(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 14 ,
(10) —(C═O) m —NR 10 R 11 ,
(11) —S(O) 2 —NR 10 R 11 ,
(12) —S(O) q —R 12 ,
(13) —CO 2 H,
(14) —CN, and
(15) —NO 2 ;
R 14 is selected from the group consisting of:
(1) hydroxyl,
(2) halogen,
(3) C 1-6 alkyl,
(4) —C 3-6 cycloalkyl,
(5) —O—C 1-6 alkyl,
(6) —O(C═O)—C 1-6 alkyl,
(7) —NH—C 1-6 alkyl,
(8) phenyl,
(9) heterocycle,
(10) —CO 2 H, and
(11) —CN;
or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 wherein A 1 is phenyl.
3 . The compound of claim 1 wherein A 1 is pyridyl.
4 . The compound of claim 1 wherein A 2 is phenyl.
5 . The compound of claim 1 wherein A 2 is heteroaryl.
6 . The compound of claim 1 wherein A 3 is phenyl.
7 . The compound of claim 1 wherein R 1a , R 1b and R 1c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or napthyl,
(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(6) heteroaryl, wherein heteroaryl is selected from pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 , and
(9) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 .
8 . The compound of claim 7 wherein R 1a , R 1b and R 1c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl or napthyl, and
(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl.
9 . The compound of claim 8 wherein R 1a , R 1b and R 1c are independently selected from the group consisting of:
(1) hydrogen,
(2) chloro,
(3) fluroro, and
(4) methyl.
10 . The compound of claim 1 wherein R 2a , R 2b and R 2c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl or napthyl,
(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(6) heteroaryl, wherein heteroaryl is selected from pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 , and
(9) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 .
11 . The compound of claim 10 wherein R 2a , R 2b and R 2c are independently selected from the group consisting of:
(1) hydrogen,
(2) chloro,
(3) fluoro,
(4) bromo,
(5) methoxy,
(6) t-butoxy,
(7) difluoromethyl, and
(8) trifluoromethyl,
(9) —N(CH 3 ).
12 . The compound of claim 1 wherein R 3a , R 3b and R 3c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or napthyl,
(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(6) heteroaryl, wherein heteroaryl is selected from pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,
(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 , and
(9) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ;
with the proviso that if A 3 is pyridyl, at least one of R 3a , R 3b and R 3c is other than hydrogen.
13 . The compound of claim 12 wherein R 3a , R 3b and R 3c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen, and
(3) C 1-6 alkyl;
with the proviso that if A 3 is pyridyl, at least one of R 3a , R 3b and R 3c is other than hydrogen.
14 . A compound which is selected from the group consisting of:
N-(3,4-Dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-6′-fluoro-2,3′-bipyridine-3-carboxamide; N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-quinolin-3-ylnicotinamide; N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(3-hydroxyphenyl)nicotinamide; N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-{3-[(methylamino)carbonyl]phenyl}-nicotinamide; N-(3,4-dimethoxybenzyl)-2-{3-[(dimethylamino)methyl]phenyl}-5-(3,5-dimethylphenyl)nicotinamide; N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)-2-(1H-indol-5-yl)nicotinamide; 5-(3,5-dimethylphenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-N-(quinolin-2-ylmethyl)nicotinamide; N-[(5,6-dimethoxypyridin-3-yl)methyl]-5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-dichlorophenyl)-N-[(2,3-dimethyl-1H-indol-6-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3-fluoro-5-methylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-N-[(1R)-1-(2-naphthyl)ethyl]nicotinamide; 5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-N-(2-naphthylmethyl)nicotinamide; 5-(3-fluoro-5-methylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-N-(2-naphthylmethyl)nicotinamide; 5-(3,5-dimethylphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-N-(quinolin-3-ylmethyl)nicotinamide; 5-(3-Chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-fluoromethylphenyl)-N-[1-(3,4-dimethoxyphenyl)ethyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-fluoromethylphenyl)-N-(3,4-dimethoxybenzyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-[(2,3-dimethyl-1-H-indol-5-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-(2-naphthylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-fluoromethylphenyl)-N-(3,4-dimethoxybenzyl)-2-pyridazin-3-yl-nicotinamide; 5-(3,5-chloromethylphenyl)-N-(3,4-dichlorobenzyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-fluoromethylphenyl)-N-[1-(3,4-dimethoxyphenyl)ethyl]-6′-fluoro-2,3′-bipyridine-3-carboxamide; 5-(3,5-dichlorophenyl)-N-(3,4-dimethoxybenzyl)-5′-chloro-2,3′-bipyridine-3-carboxamide; 5-(3,5-chloromethylphenyl)-N-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-[(1-methyl-2,3-dihydro-1H-indol-5-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-[(1,4-dimethyl-1,2,3,4-tetrahydroquinoxalin-6-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-[(1,4,5-trimethyl-1H-imidazol-2-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-fluoromethylphenyl)-N-(3,4-dimethoxybenzyl)-2-(1-methyl-1H-pyrazol-5-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-(3,4-dihydroxybenzyl)-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3,5-chloromethylphenyl)-N-[(1-methyl-1H-indol-2-yl)methyl]-2-(1-methyl-1H-pyrazol-4-yl)nicotinamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-(morpholin-4-yl)nicotinamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-piperidin-1-ylnicotinamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-pyrrolidin-1-ylnicotinamide; 2-azetidin-1-yl-5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-nicotinamide; 5-(3,5-dichlorophenyl)-N-(3,4-dimethoxybenzyl)-2-(3-methoxyazetidin-1-yl)nicotinamide; 5-(3,5-dichlorophenyl)-N-(3,4-dimethoxybenzyl)-2-(3-fluoroazetidin-1-yl)nicotinamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-[(3R)-3-fluoropyrrolidin-1-yl]nicotinamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-thiomorpholin-4-ylnicotinamide; 5-(3,5-dichlorophenyl)-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2-morpholin-4-ylnicotinamide; 5′-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-6-morpholin-4-yl-3,3′-bipyridine-5-carboxamide; N-[(5,6-dimethoxypyridin-2-yl)methyl]-5′-methyl-6-morpholin-4-yl-3,3′-bipyridine-5-carboxamide; 5-(3-chloro-5-methylphenyl)-N-[(5,6-dimethoxypyrazin-2-yl)methyl]-2-morpholin-4-ylnicotinamide; N-[4-methoxy-3-(trifluoromethyl)benzyl]-5′-methyl-6-pyrrolidin-1-yl-3,3′-bipyridine-5-carboxamide; N-(3-chloro-4-methoxybenzyl)-5′-methyl-6-pyrrolidin-1-yl-3,3′-bipyridine-5-carboxamide; 5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-N-[(1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)methyl]-3,3′-bipyridine-5-carboxamide; N-[(5,6-dimethoxypyridin-2-yl)methyl]-5-(3,5-dimethylphenyl)-2-(4-methyl-1H-pyrazol-1-yl)nicotinamide; 5-(3-chloro-5-fluorophenyl)-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2-(4-methyl-1H-pyrazol-1-yl)nicotinamide; N-(3-cyclopropyl-4-methoxybenzyl)-5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxamide; N-(3-chloro-4-methoxybenzyl)-5-(3-fluoro-5-methoxyphenyl)-2-(1H-pyrazol-1-yl)nicotinamide; N-(3-chloro-4-methoxybenzyl)-5′-methyl-6-(1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxamide; N-[(5,6-dimethoxypyridin-2-yl)methyl]-5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxamide; N-(3-ethyl-4-methoxybenzyl)-5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxamide; N-(3-chloro-4-methoxybenzyl)-5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxamide; 5-(3-chloro-5-methylphenyl)-N-(3,4-dimethoxybenzyl)-2-(4-methyl-1H-pyrazol-1-yl)nicotinamide; 6-cyclopentyl-N-[(5,6-dimethoxypyridin-2-yl)methyl]-5′-methyl-3,3′-bipyridine-5-carboxamide; 6-cyclopentyl-N-(3,4-dimethoxybenzyl)-5′-methyl-3,3′-bipyridine-5-carboxamide; N-(3-chloro-4-methoxybenzyl)-6-cyclopentyl-5′-methyl-3,3′-bipyridine-5-carboxamide; 6-cyclopentyl-N-[4-methoxy-3-(trifluoromethyl)benzyl]-5′-methyl-3,3′-bipyridine-5-carboxamide; or a pharmaceutically acceptable salt thereof.
15 . A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.
16 . (canceled)
17 . (canceled)
18 . A method for enhancing the quality of sleep in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.
19 . A method for treating insomnia in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.
20 . A method for treating or controlling obesity in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.Cited by (0)
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