Patent US1870997A successfully refreshed from Google Patents.
US5484783A
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Hypocholesterolemic, antiatherosclerotic and hypotriglyceridemic mercaptoacetylamide and benzazapine derivatives
Assignee: Aventis Pharmaceuticals Inc
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Filing: 1994-03-24
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Granted: 1996-01-16
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Expires: 2014-03-24
Abstract
Abstract The present invention relates to the use of certain mercaptoacetylamide and benzazapine derivatives in treating patients suffering from hypertriglyceridemia, atherosclerosis and hypercholesterolemia.
Inventors
- 👤 Gary A. Flynn
- 👤 John F. French
- 👤 Richard C. Dage
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 10:22
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/55; A61P; A61P3/00; A61P3/06; A61P9/00; A61P9/10
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
207 words
A method of lowering total serum cholesterol in a patient in need thereof comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR4## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 2
Independent Claim
207 words
A method of lowering total serum cholesterol in a patient in need thereof comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR4## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 3
Independent Claim
202 words
A method of treating a patient for hypercholesterolemia comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR5## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 4
Independent Claim
202 words
A method of treating a patient for hypercholesterolemia comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR5## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 5
Independent Claim
206 words
A method of lowering plasma triglycerides in a patient in need thereof comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR6## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 6
Independent Claim
206 words
A method of lowering plasma triglycerides in a patient in need thereof comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR6## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 7
Independent Claim
203 words
A method of treating a patient suffering from hypertriglyceridemia comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR7## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 8
Independent Claim
203 words
A method of treating a patient suffering from hypertriglyceridemia comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR7## wherein A 1 and A 2 are each independently hydrogen or --COOR 4 wherein R 4 is hydrogen; --CH 2 O--C(O)C(CH 3 ) 3 ; a C 1 -C 4 alkyl; an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or diphenylmethyl; with the proviso that where A 1 is hydrogen, A 2 is --COOR 4 , and where A 1 is --COOR 4 , A 2 is hydrogen; B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; and n is an integer 0 or 1.
Claim 9
Independent Claim
193 words
A method of lowering total serum cholesterol in a patient in need thereof comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR8## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR9## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 10
Independent Claim
193 words
A method of lowering total serum cholesterol in a patient in need thereof comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR8## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR9## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 11
Independent Claim
188 words
A method of treating a patient for hypercholesterolemia comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR10## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR11## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 12
Independent Claim
188 words
A method of treating a patient for hypercholesterolemia comprising administering to said patient a therapeutically effective hypocholesterolemic amount of a compound of the Formula ##STR10## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR11## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 13
Independent Claim
192 words
A method of lowering plasma triglycerides in a patient in need thereof comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR12## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR13## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 14
Independent Claim
192 words
A method of lowering plasma triglycerides in a patient in need thereof comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR12## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR13## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 15
Independent Claim
189 words
A method of treating a patient suffering from hypertriglyceridemia comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR14## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR15## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 16
Independent Claim
189 words
A method of treating a patient suffering from hypertriglyceridemia comprising administering to said patient a therapeutically effective hypotriglyceridemic amount of a compound of the Formula ##STR14## wherein B 1 and B 2 are each independently hydrogen; hydroxy; --OR 5 wherein R 5 is a C 1 -C 4 alkyl or an Ar--Y-- group wherein Ar is aryl and Y is a C 0 -C 4 alkyl; or, where B 1 and B 2 are attached to adjacent carbon atoms, B 1 and B 2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; R 2 is hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group; R 3 is hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 4 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group, --CH 2 O--C(O)C(CH 3 ) 3 or diphenylmethyl; and ##STR15## wherein R 6 is hydrogen, a C 1 -C 4 alkyl or an Ar--Y-- group and R 7 is --CF 3 , a C 1 -C 10 alkyl or an Ar--Y-- group.
Claim 17
Independent Claim
16 words
A method according to any of claims 1-8 wherein the compound is [4S-[4α, 7α(R*), 12bβ]]-7-[(1-oxo-2(S)-acetylthio-3-phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo-pyrido[2,1-a][2]benzazepine-4-carboxylic acid.
Claim 18
Independent Claim
16 words
A method according to any of claims 1-8 wherein the compound is [4S-[4α, 7α(R*), 12bβ]]-7-[(1-oxo-2(S)-thio-3-phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a][2]benzazepine-4-carboxylic acid.
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