US4808581A
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Imidazolyl- indolylpropanones as 5-HT3 receptor antagonists
Assignee: Glaxo Group Ltd
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Filing: 1988-01-22
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Granted: 1989-02-28
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Expires: 2008-01-22
Abstract
Abstract The invention relates to compounds of formula (I): ##STR1## and physiologically acceptable salts or solvates thereof, wherein Im represents an imidazolyl group of formula: ##STR2## and the various substituents are defined hereinbelow. The compounds are potent and selective antagonists of the effect of 5-HT at 5-HT 3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety, and nausea and vomiting.
Inventors
- 👤 Alexander W. Oxford
- 👤 David J. Cavalla
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 20:18
CPC Classifications
C; C07; C07D; C07D403/00; C07D403/02; C07D403/06
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
413 words
A compound of formula (I): ##STR15## or a physiologically acceptable salt or solvate thereof, wherein Im represents an imidazolyl group of formula: ##STR16## R 1 represents a hydrogen atom, or a group selected from C 1-6 alkyl, C 3-6 alkenyl, C 3-10 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, phenyl, phenylC 1-3 alkyl, --CO 2 R 8 , --COR 8 , --CONR 8 R 9 or --SO 2 R 8 (wherein R 8 and R 9 , 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 phenylC 1-4 alkyl group, in which the phenyl group is unsubstituted or substituted by one of more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 8 does not represent a hydrogen atom when R 1 represents a group --CO 2 R 8 or --SO 2 R 8 ); R 2 represents a hydrogen atom or a C 1-6 alkyl, C 3-6 alkenyl, C 3-7 cycloalkyl, phenyl or phenylC 1-3 alkyl group; A-B represents the group R 3 R 4 C--CH 2 or R 3 C═CH; R 3 and R 4 , which may be the same or different, each represents a hydrogen atom or a C 1-6 alkyl group; one of the groups represented by R 5 , R 6 and R 7 represents a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 3-6 alkenyl, phenyl or phenylC 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; Q represents a hydrogen or a halogen atom or a hydroxy, C 1-4 alkoxy, phenylC 1-3 alkoxy or C 1-6 alkyl group or a group --NR 10 R 11 or CONR 10 R 11 (wherein R 10 and R 11 , which may be the same or different, each represents a hydrogen atom or a C 1-4 alkyl or C 3-4 alkenyl group, or together with the nitrogen atom to which they are attached form a saturated 5 or 7 membered ring); and with the proviso that when A-B represents the group R 3 C═CH, Q represents a hydrogen atom and R 1 represents a hydrogen atom or a C 1-6 alkyl, C 3-6 alkenyl, C 3-10 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, phenyl or phenylC 1-3 alkyl group.
Claim 2
Dependent Claim
413 words
A compound of formula (I): ##STR15## or a physiologically acceptable salt or solvate thereof, wherein Im represents an imidazolyl group of formula: ##STR16## R 1 represents a hydrogen atom, or a group selected from C 1-6 alkyl, C 3-6 alkenyl, C 3-10 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, phenyl, phenylC 1-3 alkyl, --CO 2 R 8 , --COR 8 , --CONR 8 R 9 or --SO 2 R 8 (wherein R 8 and R 9 , 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 phenylC 1-4 alkyl group, in which the phenyl group is unsubstituted or substituted by one of more C 1-4 alkyl, C 1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R 8 does not represent a hydrogen atom when R 1 represents a group --CO 2 R 8 or --SO 2 R 8 ); R 2 represents a hydrogen atom or a C 1-6 alkyl, C 3-6 alkenyl, C 3-7 cycloalkyl, phenyl or phenylC 1-3 alkyl group; A-B represents the group R 3 R 4 C--CH 2 or R 3 C═CH; R 3 and R 4 , which may be the same or different, each represents a hydrogen atom or a C 1-6 alkyl group; one of the groups represented by R 5 , R 6 and R 7 represents a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, C 3-6 alkenyl, phenyl or phenylC 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; Q represents a hydrogen or a halogen atom or a hydroxy, C 1-4 alkoxy, phenylC 1-3 alkoxy or C 1-6 alkyl group or a group --NR 10 R 11 or CONR 10 R 11 (wherein R 10 and R 11 , which may be the same or different, each represents a hydrogen atom or a C 1-4 alkyl or C 3-4 alkenyl group, or together with the nitrogen atom to which they are attached form a saturated 5 or 7 membered ring); and with the proviso that when A-B represents the group R 3 C═CH, Q represents a hydrogen atom and R 1 represents a hydrogen atom or a C 1-6 alkyl, C 3-6 alkenyl, C 3-10 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, phenyl or phenylC 1-3 alkyl group.
Claim 3
Dependent Claim
55 words
A compound according to claim 1 of formula (Ia): ##STR17## wherein R 1 represents a hydrogen atom or a C 1-6 alkyl, C 3-6 alkenyl, C 3-10 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, phenyl or phenylC 1-3 alkyl group; and R 2 , A-B and Im are as defined in claim 1.
Claim 4
Dependent Claim
34 words
A compound according to claim 2 in which R 1 represents a hydrogen atom or a C 1-3 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 5-6 cycloalkyl, C 5-6 cycloalkylmethyl or benzyl group.
Claim 5
Dependent Claim
22 words
A compound according to claim 2 in which R 2 represents a hydrogen atom or a C 1-3 alkyl or phenyl group.
Claim 6
Dependent Claim
36 words
A compound according to claim 2 in which A-B represents CH═CH or R 3 R 4 C--CH 2 where R 3 and R 4 each independently represent a hydrogen atom or a C 1-3 alkyl group.
Claim 7
Dependent Claim
42 words
A compound according to claim 2 in which R 5 and R 7 each represent a hydrogen atom or a C 1-3 alkyl group, and R 6 represents a hydrogen atom or a C 1-3 alkyl, C 3-4 alkenyl or benzyl group.
Claim 8
Dependent Claim
92 words
A compound according to claim 2 in which R 1 represents a hydrogen atom or a C 1-3 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 5-6 cycloalkyl, or benzyl group; R 2 represents a hydrogen atom or a C 1-3 alkyl group; A-B represents CH═CH or R 3 R 4 C--CH 2 where R 3 and R 4 each independently represent a hydrogen atom or a C 1-3 alkyl group; and R 5 , R 6 and R 7 each independently represent a hydrogen atom or a C 1-3 alkyl group.
Claim 9
Dependent Claim
78 words
A compound according to claim 2 in which R 1 represents a hydrogen atom or a methyl, prop-2-enyl or cyclopentyl group; R 2 represents a hydrogen atom or a methyl group; A-B represents CR 3 R 4 --CH 2 where R 3 and R 4 each independently represent a hydrogen atom or a methyl group; R 5 and R 6 each represent a hydrogen atom; and R 7 represents a hydrogen atom or a C 1-3 alkyl group.
Claim 10
Dependent Claim
43 words
A compound according to claim 2 in which A-B represents R 3 R 4 C--CH 2 and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined in claim 2.
Claim 11
Dependent Claim
64 words
A compound according to claim 1 of formula (Ib): ##STR18## wherein R 1 , R 2 , R 3 , R 4 , Q and Im are as defined in claim 1, and with the proviso that when Q represents a hydrogen atom, R 1 represents --CO 2 R 8 , --COR 8 , --CONR 8 R 9 or --SO 2 R 8 .
Claim 12
Dependent Claim
37 words
A compound according to claim 10 in which R 1 represents a hydrogen atom or a C 1-3 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 5-6 cycloalkyl, benzyl, N,N-diC 1-3 alkylcarboxamido or C 1-3 alkoxycarbonyl group.
Claim 13
Dependent Claim
20 words
A compound according to claim 10 in which R 2 represents a hydrogen atom or a C 1-3 alkyl group.
Claim 14
Dependent Claim
25 words
A compound according to claim 10 in which R 3 and R 4 each independently represent a hydrogen atom or a C 1-3 alkyl group.
Claim 15
Dependent Claim
27 words
A compound according to claim 10 in which R 5 , R 6 and R 7 each represent a hydrogen atom or a C 1-3 alkyl group.
Claim 16
Dependent Claim
36 words
A compound according to claim 10 in which R 5 and R 6 both represent hydrogen atoms and R 7 represents a C 1-6 alkyl, C 3-7 cycloalkyl, C 3-6 alkenyl or phenylC 1-3 alkyl group.
Claim 17
Dependent Claim
28 words
A compound according to claim 10 in which Q represents a hydrogen atom, a halogen atom or a hydroxy, C 1-3 alkoxy, or a C 1-3 alkyl group.
Claim 18
Dependent Claim
75 words
A compound according to claim 10 in which R 1 represents a C 1-3 alkyl, N,N-deC 1-3 alkylcarboxamido or C 1-3 alkoxycarbonyl group; R 2 represents a hydrogen atom; R 3 and R 4 both represent hydrogen atoms; R 5 and R 6 each represent a hydrogen atom; R 7 represents a hydrogen atom or a C 1-3 alkyl group; and Q represents a hydrogen or a halogen atom or a C 1-3 alkyl group.
Claim 19
Dependent Claim
17 words
A compound selected from: 3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 2-methyl-3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 3-(5-methyl-1H-imidazol-4-yl)-1-(1,2-dimethyl-1H-indol-3-yl)-1-propanone; 1-(1-methyl-1H-indol-3-yl)-3-(5-propyl-1H-imidazol-4-yl)-1-propanone; 2,2-dimethyl-3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 3-(5-methyl-1H-imidazol-4-yl)-1-(1,7-dimethyl-1H-indol-3-yl)propanone; and physiologically acceptable salts and solvates thereof.
Claim 20
Dependent Claim
17 words
A compound selected from: 3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 2-methyl-3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 3-(5-methyl-1H-imidazol-4-yl)-1-(1,2-dimethyl-1H-indol-3-yl)-1-propanone; 1-(1-methyl-1H-indol-3-yl)-3-(5-propyl-1H-imidazol-4-yl)-1-propanone; 2,2-dimethyl-3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone; 3-(5-methyl-1H-imidazol-4-yl)-1-(1,7-dimethyl-1H-indol-3-yl)propanone; and physiologically acceptable salts and solvates thereof.
Claim 21
Dependent Claim
58 words
A pharmaceutical composition for the treatment of a condition selected from the psychotic disorders, anxiety, and nausea and vomiting 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 22
Dependent Claim
45 words
A method of treating a condition caused by disturbance of "neuronal" 5HT function which 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 23
Dependent Claim
47 words
A method of treating a condition selected from psychotic disorders, anxiety, and nausea and vomiting which comprises administering to a patient an effective amount to relieve said condition of a compound of formula (I) as defined in claim 1 or a physiologically acceptable salt or solvate thereof.
Claim 24
Dependent Claim
59 words
A pharmaceutical composition for the treatment of a condition selected from gastric stasis, symptoms of gastro-intestinal dysfunction, migraine and pain 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 25
Dependent Claim
49 words
A method of treating a condition selected from gastric stasis, symptoms of gastrointestinal dysfunction, migraine and pain which comprises administering to a patient an effective amount to relieve said condition of a compound of formula (I) as defined in claim 1 or a physiologically acceptable salt or solvate thereof.
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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) | 1992-02-28 | 1992-08-29 | 1993-02-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-02-28 | 1996-08-29 | 1997-02-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-02-28 | 2000-08-29 | 2001-02-28 | $7700.00 | Window Closed / Lapsed |