US4757151A
Expired / Lapsed
US
⏱️ 0.0 years remaining
2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl]
Assignee: Warner Lambert UK Ltd
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Filing: 1986-09-30
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Granted: 1988-07-12
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Expires: 2006-09-30
Abstract
Abstract Certain 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl]propanamides demonstrate activity as appetite suppressants. The compounds, pharmaceutical compositions, and a method of suppressing appetite are disclosed.
Inventors
- 👤 David C. Horwell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 23:23
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/12; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/18; C07D209/20; C07D405/00; C07D405/02; C07D405/12; C07D409/00; C07D409/02; C07D409/12; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06139; C07K5/06156
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
381 words
A compound having structural formula 1: ##STR13## wherein A is --NH--, ##STR14## or --(CH 2 ) n , where n is an integer of from zero to six; R 1 is an N-terminal blocking group selected from ##STR15## R 2 is straight or branched alkyl of from one to six carbon atoms, trifluoromethyl, --CH 2 --CH═CH 2 , --CH 2 --C═CH, --CH 2 OR, --(CH 2 ) m COOR, --(CH 2 ) m NR 6 R 7 , --CH 2 Ar or -CH 2 OAr, where m is an integer of from one to six, R, R 6 and R 7 are selected from hydrogen, or straight or branched alkyl of from one to six carbon atoms, and Ar is 2-, or 3-thienyl, 2-, 3-, or 4-pyridinyl, or ##STR16## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the provisos that when X is nitro, Y is hydrogen, and R 3 is hydrogen, straight or branched alkyl of from one to six carbon atoms, trifluoromethyl, --CH 2 --CH═ 2 , CH═--CH 2 --C.tbd.CH, --CH 2 OR, --(CH 2 ) m COOR, --(CH 2 ) m NR 6 R 7 , --CH 2 Ar or --CH 2 OAr, where m is an integer of from one to six, R, R 6 , and R 7 are selected from hydrogen, or straight or branched alkyl of from one to six carbon atoms, and Ar is 2-, or 3-thienyl, 2-, 3-, or 4-pyridinyl, or ##STR17## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the provisos that when X is nitro, Y is hydrogen, and R 4 is hydrogen, --CH 2 OH, ##STR18## where Z is --CH 2 --, NR, where R is as previously defined, oxygen, sulfur --CONR 6 R 7 , --CH 2 NR 6 R 7 , or --COOR where R, R 6 , and R 7 are as previously defined, and R 5 is 2- or 3-thienyl, 2-, 3-, or 4-pyridinyl, 2- or 3-indanyl, cyclohexyl, 2- or 3-furanyl, 3- or 4-pyridazinyl, 2-imidazolyl, 2-benzimidazolyl, 2-tetrahydrobenzimidazolyl, 2-perimidyl, or ##STR19## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the proviso that when X is nitro, Y is hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
381 words
A compound having structural formula 1: ##STR13## wherein A is --NH--, ##STR14## or --(CH 2 ) n , where n is an integer of from zero to six; R 1 is an N-terminal blocking group selected from ##STR15## R 2 is straight or branched alkyl of from one to six carbon atoms, trifluoromethyl, --CH 2 --CH═CH 2 , --CH 2 --C═CH, --CH 2 OR, --(CH 2 ) m COOR, --(CH 2 ) m NR 6 R 7 , --CH 2 Ar or -CH 2 OAr, where m is an integer of from one to six, R, R 6 and R 7 are selected from hydrogen, or straight or branched alkyl of from one to six carbon atoms, and Ar is 2-, or 3-thienyl, 2-, 3-, or 4-pyridinyl, or ##STR16## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the provisos that when X is nitro, Y is hydrogen, and R 3 is hydrogen, straight or branched alkyl of from one to six carbon atoms, trifluoromethyl, --CH 2 --CH═ 2 , CH═--CH 2 --C.tbd.CH, --CH 2 OR, --(CH 2 ) m COOR, --(CH 2 ) m NR 6 R 7 , --CH 2 Ar or --CH 2 OAr, where m is an integer of from one to six, R, R 6 , and R 7 are selected from hydrogen, or straight or branched alkyl of from one to six carbon atoms, and Ar is 2-, or 3-thienyl, 2-, 3-, or 4-pyridinyl, or ##STR17## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the provisos that when X is nitro, Y is hydrogen, and R 4 is hydrogen, --CH 2 OH, ##STR18## where Z is --CH 2 --, NR, where R is as previously defined, oxygen, sulfur --CONR 6 R 7 , --CH 2 NR 6 R 7 , or --COOR where R, R 6 , and R 7 are as previously defined, and R 5 is 2- or 3-thienyl, 2-, 3-, or 4-pyridinyl, 2- or 3-indanyl, cyclohexyl, 2- or 3-furanyl, 3- or 4-pyridazinyl, 2-imidazolyl, 2-benzimidazolyl, 2-tetrahydrobenzimidazolyl, 2-perimidyl, or ##STR19## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the proviso that when X is nitro, Y is hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
12 words
A compound as defined by claim 1 wherein R 2 is methyl.
Claim 4
Dependent Claim
17 words
A compound as defined by claim 1 wherein R 4 is hydrogen, hydroxymethyl, or --CONH 2 .
Claim 5
Dependent Claim
12 words
A compound as defined by claim 1 wherein R 5 is phenyl.
Claim 6
Dependent Claim
37 words
A compound as defined by claim 1 wherein R 5 is ##STR20## where X and Y are independently hydrogen, fluorine, chlorine, methyl, methoxyl, trifluoromethyl, or nitro, with the proviso that when X is nitro, Y is hydrogen.
Claim 7
Dependent Claim
15 words
A compound as defined by claim 1 wherein R 5 is 2-, 3-, or 4-pyridinyl.
Claim 8
Dependent Claim
29 words
A compound as defined by claim 1 wherein R 5 is 2- or 3-thienyl, 2- or 3-indanyl, 2- or 3-furanyl, 3- or 4-pyridazinyl, 2-imidazolyl, 2-benzimidazolyl, 2-tetrahydrobenzimidazolyl, 2-perimidyl, or cyclohexyl.
Claim 9
Dependent Claim
11 words
A compound as defined by claim 1 having the name N-[(1,1-dimethylethoxy)carbonyl]-α-DL-methyl-tryptophyl-L-phenylalaninamide.
Claim 10
Dependent Claim
12 words
A compound as defined by claim 1 having the name N-[(9H-fluoren-9-ylmethoxy carbonyl]-α-methyl-DL-tryptophyl-L-phenylalaninamide.
Claim 11
Dependent Claim
14 words
A compound as defined by claim 1 having the name [1-(1H-indole-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 12
Dependent Claim
14 words
A compound as defined by claim 1 having the name [2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-1-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 13
Dependent Claim
14 words
A compound as defined by claim 1 having the name (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 14
Dependent Claim
14 words
A compound as defined by claim 1 having the name (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester.
Claim 15
Dependent Claim
14 words
A compound as defined by claim 1 having the name (±)-[2-[(2-phenylethyl)amino]-1-(1H-indol-3-yl-methyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethyl ester.
Claim 16
Dependent Claim
14 words
A compound as defined by claim 1 having the name (±)-[2-[(2-phenylethyl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloroethyl ester.
Claim 17
Dependent Claim
14 words
A compound as defined by claim 1 having the name [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-oxo-2-(1-piperidinyl)-1-(phenylmethyl)ethyl]amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 18
Dependent Claim
14 words
A compound as defined by claim 1 having the name [2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester.
Claim 19
Dependent Claim
17 words
A compound as defined by claim 1 having the name [2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester, pentanedioate salt (2:1).
Claim 20
Dependent Claim
11 words
A compound as defined by claim 1 having the name N-[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]tryptophylphenylalaninamide.
Claim 21
Dependent Claim
14 words
A compound as defined by claim 1 having the name [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 2,2,2-trifluoro-1,1-dimethyl ester.
Claim 22
Dependent Claim
14 words
A compound as defined by claim 1 having the name (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(3-pyridinyl)ethyl]amino]ethyl]carbamic acid, 1,1dimethylpropyl ester.
Claim 23
Dependent Claim
40 words
A compound as defined by claim 4 selected from the group consisting of (±)-α-amino-α-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide; (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamic acid, 9H-fluoren-9-ylmethyl ester; (±)-α-[(2,3-dimethyl-1-oxobutyl)amino]-α-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide; (±)-α-[[[(1,1-dimethylethyl)amino]carbonyl]amino]α-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide; (R)-[2-[(1,1-dimethyl-2-phenylethyl)amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]carbamic acid, 1,1-dimethylpropylester; (S)-[2-[(1,1-dimethyl-2-phenylethyl)amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]carbamic acid, 1,1-dimethylpropylester; [2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester; N-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(4-phenylbutyl)amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester; N-[(1,1-dimethylpropoxy)carbonyl]-DL-tryptophyl-L-phenylalanine, methyl ester; and N-[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]-L-tryptophyl-N.sup.α -methyl-DL-phenylalaninamide.
Claim 24
Dependent Claim
25 words
A compound as defined by claim 5 selected from the group consisting of: (±)-[1-(1H-indol-3-ylmethyl)-2-[[2-(4-methoxyphenyl)ethyl]amino]-1-methyl-2-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester; (±)-[2-[[2-(4-chlorophenyl)ethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester; (±)-[2-[[2-(3,4-dichlorophenyl)ethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester
Claim 25
Dependent Claim
36 words
A compound as defined by claim 6 selected from the group consisting of (R)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester; (±)-[1-(1H-indol-3-ylmethyl)-1-[[[2-(2-pyridinyl)ethyl]amino]carbonyl]propyl]carbamic acid, 2,2,2-trichloroethyl ester; [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2- (2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 2,2,2-tri-fluoro-1,1-dimethyl ester; [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2- (2-pyridinyl)ethyl]amino]ethyl]carbamic acid, 2,2-difluoro-1-(fluoromethyl)ethyl ester; and (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(4-pyridinyl)ethyl]amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 26
Dependent Claim
54 words
A compound as defined by claim 7 selected from the group consisting of: (±)-[2-[(2,3-dihydro-1H-inden-1-yl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester; (±) [2-[(2,3-dihydro-1H-inden-2-yl)amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 2,2,2-trichloro-1,1-dimethylethyl ester; [2-[[2-amino-2-oxo-1-(2-thienylmethyl)ethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethy-1]- carbamic acid, 1,1-dimethylpropyl ester; (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-thienylethyl)amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester; (±)-[2-[[2-(2-furanyl)ethyl]amino-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester; (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(3-pyridazinyl)ethyl]amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester; (±)-[2- [[2-(1H-benzimidazol-2-yl)ethyl]ethyl]amino]-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethy-1]- carbamic acid, 1,1-dimethylpropyl ester; [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(1H-perimidin-2-yl)ethyl]amino]ethyl]carbamic acid, 1,1-dimethylpropyl ester; and (±)-[2-[(2-cyclohexylethyl)amino]-1-(1H-indol-3-yl)methyl)-1-methyl-2-oxoethyl]carbamic acid, 1,1-dimethylpropyl ester.
Claim 27
Dependent Claim
29 words
A pharmaceutical composition comprising an amount of a compound as defined by claim 1 effective to suppress the food intake of a mammal together with a pharmaceutically acceptable carrier.
Claim 28
Dependent Claim
34 words
A method of suppressing the food intake of a mammal comprising administering to a mammal in need of such treatment an appetite suppressing effective amount of a pharmaceutical composition as defined by claim 26.
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