US4749718A
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Carbazole derivatives and their use as 5HT-induced antagonists
Assignee: Glaxo Group Ltd
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Filing: 1986-07-23
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Granted: 1988-06-07
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Expires: 2006-07-23
Abstract
Abstract The invention relates to compounds of the general formula (I): ##STR1## wherein R 1 represents a group CO 2 R 5 , COR 5 , CONR 5 R 6 or SO 2 R 5 (wherein R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a C 1-6 alkyl or C 3-7 cycloalkyl group, or a phenyl or phenyl-(C 1-4 )alkyl group in which the phenyl group is optionally substituted by one or more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 5 does not represent a hydrogen atom when R 1 represents a group CO 2 R 5 or SO 2 R 5 ); and one of the groups represented by R 2 , R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl or phenyl-(C 1-3 )alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-6 alkyl group; and physiologically acceptable salts and solvates thereof. The compounds are potent and selective antagonists of "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; pain; gastric stasis; symptoms of gastrointestinal dysfunction such as occur with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence; migraine; and nausea and vomiting.
Inventors
- 👤 Ian H. Coates
- 👤 James A. Bell
- 👤 David C. Humber
- 👤 George B. Ewan
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 21:14
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; A; A61; A61P; A61P1/00; A61P1/04; A61P1/08; A61P25/00; A61P25/04; A61P43/00; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08; C07D403/00; C07D403/02; C07D403/06
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
183 words
A compound of formula (I): ##STR17## wherein R 1 represents a group CO 2 R 5 , COR 5 , CONR 5 R 6 or SO 2 R 5 (wherein R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a C 1-6 alkyl or C 3-7 cycloalkyl group, or a phenyl or phenyl-(C 1-4 )alkyl group in which the phenyl group is optionally substituted by one or more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 5 does not represent a hydrogen atom when R 1 represents a group CO 2 R 5 or SO 2 R 5 ); and one of the groups represented by R 2 , R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl or phenyl-(C 1-3 )alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-6 alkyl group; or physiologically acceptable salt or solvate thereof.
Claim 2
Dependent Claim
183 words
A compound of formula (I): ##STR17## wherein R 1 represents a group CO 2 R 5 , COR 5 , CONR 5 R 6 or SO 2 R 5 (wherein R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a C 1-6 alkyl or C 3-7 cycloalkyl group, or a phenyl or phenyl-(C 1-4 )alkyl group in which the phenyl group is optionally substituted by one or more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 5 does not represent a hydrogen atom when R 1 represents a group CO 2 R 5 or SO 2 R 5 ); and one of the groups represented by R 2 , R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl or phenyl-(C 1-3 )alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-6 alkyl group; or physiologically acceptable salt or solvate thereof.
Claim 3
Dependent Claim
60 words
A compound as claimed in claim 1, in which one of the groups represented by R 2 , R 3 and R 4 represents a C 1-3 alkyl, C 3-6 cycloalkyl or C 3-6 alkenyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-3 alkyl group.
Claim 4
Dependent Claim
31 words
A compound as claimed in claim 1 in which R 2 represents a hydrogen atom and one of the groups R 3 and R 4 represents a C 1-3 alkyl group.
Claim 5
Dependent Claim
28 words
A compound as claimed in claim 1 in which R 2 represents a hydrogen atom and R 3 and R 4 both represent a C 1-3 alkyl group.
Claim 6
Dependent Claim
28 words
A compound as claimed in claim 1 in which R 2 represents a C 1-3 alkyl group and R 3 and R 3 both represent a hydrogen atom.
Claim 7
Dependent Claim
39 words
A compound as claimed in claim 1 in which R 5 and R 6 (which may be the same or different) represent a C 1-6 alkyl group; or a phenyl group optionally substituted by a C 1-4 alkyl group.
Claim 8
Dependent Claim
22 words
A compound selected from the group consisting of 1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-1-yl)methyl]-9-(methylsulphonyl)-4H-carbazol-4-one; 1,2,3,9-tetrahydro-9-(methoxycarbonyl)-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4e,uns/H/ -carbazol-4-one; 1,2,3,9-tetrahydro-9-(4-methylbenzenesulphonyl)-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one; 9-acetyl-1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one; 1,2,3,4-tetrahydro-N,N-dimethyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4-oxo-9H-carbazole-9-carboxamide; a physiologically acceptable salt or a solvate thereof.
Claim 9
Dependent Claim
22 words
A compound selected from the group consisting of 1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-1-yl)methyl]-9-(methylsulphonyl)-4H-carbazol-4-one; 1,2,3,9-tetrahydro-9-(methoxycarbonyl)-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4e,uns/H/ -carbazol-4-one; 1,2,3,9-tetrahydro-9-(4-methylbenzenesulphonyl)-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one; 9-acetyl-1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one; 1,2,3,4-tetrahydro-N,N-dimethyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4-oxo-9H-carbazole-9-carboxamide; a physiologically acceptable salt or a solvate thereof.
Claim 10
Dependent Claim
55 words
A pharmaceutical composition for the treatment of a condition caused by disturbance of "neuronal" 5HT function comprising at least one compound of formula (I) as defined in claim 1 or a physiologically acceptable salt or solvate thereof in an amount effective to relieve said condition together with at least one physiologically acceptable carrier or excipient.
Claim 11
Dependent Claim
45 words
A method of treating a condition caused by disturbance of "neuronal" 5HT function with comprises administering to a patient an effective amount of a compound of formula (I) as defined in claim 1 or a physiologically acceptable salt or solvate thereof to relieve said condition.
Claim 12
Dependent Claim
186 words
A compound of formula (VI) ##STR18## wherein R 1 represents a group CO 2 R 5 , COR 5 , CONR 5 R 6 or SO 2 R 5 (wherein R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a C 1-6 alkyl or C 3-7 cycloalkyl group, or a phenyl or phenyl-(C 1-4 )alkyl group in which the phenyl group is optionally substituted by one or more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 5 does not represent a hydrogen atom when R 1 represents a group CO 2 R 5 or SO 2 R 5 ); and one of the groups represented by R 2 , R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl or phenyl-(C 1-3 )alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-6 alkyl group; and A represents a hydrogen atom or a hydroxyl group.
Claim 13
Dependent Claim
186 words
A compound of formula (VI) ##STR18## wherein R 1 represents a group CO 2 R 5 , COR 5 , CONR 5 R 6 or SO 2 R 5 (wherein R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a C 1-6 alkyl or C 3-7 cycloalkyl group, or a phenyl or phenyl-(C 1-4 )alkyl group in which the phenyl group is optionally substituted by one or more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 5 does not represent a hydrogen atom when R 1 represents a group CO 2 R 5 or SO 2 R 5 ); and one of the groups represented by R 2 , R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl or phenyl-(C 1-3 )alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C 1-6 alkyl group; and A represents a hydrogen atom or a hydroxyl group.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1991-06-07 | 1991-12-07 | 1992-06-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-06-07 | 1995-12-07 | 1996-06-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-06-07 | 1999-12-07 | 2000-06-07 | $7700.00 | Window Closed / Lapsed |