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US4792561A
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Carbostyril derivatives as combined thromboxane synthetase and cyclic-AMP phosphodiesterase inhibitors
Assignee: Syntex USA LLC
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Filing: 1986-05-29
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Granted: 1988-12-20
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Expires: 2006-05-29
Abstract
Abstract The invention concerns a method of inhibiting both thromboxane synthetase and cyclic-AMP phosphodiesterase in a mammal having a disease characterized by elevated thromboxane levels or an imbalance of prostacyclin/thromboxane levels with a compound of the formula: <IMAGE> (I) or a pharmaceutically acceptable acid addition salt or ester thereof, wherein: X is chosen from the group consisting of: <IMAGE> and a covalent bond in which R1 is H, alkyl having 1-6 carbon atoms, optionally substituted phenyl or optionally substituted phenyl lower alkyl, when R2 is H or OH, or R1 and R2 taken together represent oxo, alkylidene having 1-6 carbon atoms or optionally substituted benzylidene; R3 is H or alkyl having 1-6 carbon atoms, R4 is H and R3 and R4 are either cis or trans to each other, or R3 and R4 taken together represent a covalent bond; n is an integer from 0-3; Het is 1-imidazolyl or 3-pyridyl; and the dotted line represents an optional covalent bond.
Inventors
- 👤 Keith A. M. Walker
- 👤 John J. Bruno
- 👤 Gregory R. Martinez
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 20:58
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08; C07D401/00; C07D401/02; C07D401/04; C07D401/06
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
166 words
A compound of the formula: ##STR39## or a pharmaceutically acceptable acid addition salt or ester thereof, wherein: X is chosen from the group consisting of: ##STR40## in which R 1 is H when R 2 is OH, or R 1 is phenyl or phenyl lower alkyl when R 2 is H or OH, wherein the phenyl radical is optionally monosubstituted with lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or halogen, or R 1 and R 2 taken together represents oxo, alkylidene having 1-6 carbon atoms or optionally substituted benzylidene wherein the phenyl radical of the benzylidene group is optionally monosubstituted with lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or halogen; R 3 is H or alkyl having 1-6 carbon atoms, R 4 is H and R 3 and R 4 are either cis or trans to each other, or R 3 and R 4 taken together represent a covalent bond; n is an integer from 0-3; Het is 1-imidazolyl; and the dotted line represents an optional covalent bond.
Claim 2
Dependent Claim
166 words
A compound of the formula: ##STR39## or a pharmaceutically acceptable acid addition salt or ester thereof, wherein: X is chosen from the group consisting of: ##STR40## in which R 1 is H when R 2 is OH, or R 1 is phenyl or phenyl lower alkyl when R 2 is H or OH, wherein the phenyl radical is optionally monosubstituted with lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or halogen, or R 1 and R 2 taken together represents oxo, alkylidene having 1-6 carbon atoms or optionally substituted benzylidene wherein the phenyl radical of the benzylidene group is optionally monosubstituted with lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or halogen; R 3 is H or alkyl having 1-6 carbon atoms, R 4 is H and R 3 and R 4 are either cis or trans to each other, or R 3 and R 4 taken together represent a covalent bond; n is an integer from 0-3; Het is 1-imidazolyl; and the dotted line represents an optional covalent bond.
Claim 3
Dependent Claim
9 words
The compound of claim 1, wherein X is ##STR41##
Claim 4
Dependent Claim
26 words
The compound of claim 2, wherein R 1 and R 2 taken together represent alkylidene having 1-3 carbon atoms and n is an integer from 1-3.
Claim 5
Dependent Claim
18 words
The compound of claim 2, wherein R 1 is phenyl, R 2 is H and n is 0.
Claim 6
Dependent Claim
24 words
The compound of claim 4, wherein R 1 is phenyl and the optional covalent bond represented by the dotted line is absent, namely 6-[phenyl(imidazol-1-yl)methyl]-3,4-dihydrocarbostyril.
Claim 7
Dependent Claim
24 words
The compound of claim 4, wherein R 1 is phenyl and the optional covalent bond represented by the dotted line is present, namely 6-[phenyl(imidazol-1-yl)methyl]carbostyril.
Claim 8
Dependent Claim
15 words
The compound of claim 1, wherein X is ##STR42## and n is 0 or 1.
Claim 9
Dependent Claim
17 words
The compound of claim 7, wherein R 3 and R 4 taken together represent a covalent bond.
Claim 10
Dependent Claim
22 words
The compound of claim 7, wherein R 3 is H or lower alkyl having 1-3 carbon atoms and R 4 is H.
Claim 11
Dependent Claim
27 words
The compound of claim 9, wherein R 3 is methyl, n is 0 and the optional covalent bond represented by the dotted line is absent, namely 6-[1-methyl-2-(imidazol-1-yl)ethenyl]-3,4-dihydrocarbostyril.
Claim 12
Dependent Claim
27 words
The compound of claim 9, wherein R 3 is H, n is 0 and the optional covalent bond represented by the dotted line is absent, namely 6-[2-(imidazol-1-yl)ethenyl]-3,4-dihydrocarbostyril.
Claim 13
Dependent Claim
27 words
The compound of claim 9, wherein R 3 is H, n is 0 and the optional covalent bond represented by the dotted line is present, namely 6-[2-(imidazol-1-yl)ethenyl]carbostyril.
Claim 14
Dependent Claim
26 words
The compound of claim 9, wherein R 3 is H, n is 1 and the optional covalent represented by the dotted line is absent, namely 6-[3-(imidazol-1-yl)prop-1-en-1-yl]-3,4-dihydrocarbostyril.
Claim 15
Dependent Claim
43 words
A pharmaceutical composition for administration to a mammal having a disease characterized by elevated thromboxane levels or an imbalance of prostacyclin/thromboxane levels, which comprises a therapeutically effective amount of a compound of claim 1 in admixture with one or more pharmaceutically acceptable excipients.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-12-20 | 1992-06-20 | 1992-12-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-12-20 | 1996-06-20 | 1996-12-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-12-20 | 2000-06-20 | 2000-12-20 | $7700.00 | Window Closed / Lapsed |