Glaxo Group Limited

Glaxo Laboratories Limited

Sanofi

David C Humber

George B Ewan

Ian H Coates

James A Bell

Michael B Tyers

Gordon H Phillipps

Barry A Coomber

William L Mitchell

John Bradshaw

Alexander W Oxford

Barry J Price

Gordon G Weingarten

Stuart B Laing

Colin David Eldred

Brian Laundon

Brian Richard Cowley

David B Ewan

Anthony J Pateman

Neil Godfrey

Medicaments

The invention relates to the use of compounds of the general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4) alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-C.sub.1-3 alkyl group; and one of the groups represented by

Medicaments for treating nausea and vomiting

The invention relates to the use of compounds of the general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.-7 cycloalkyl-(C.sub.1-4) alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-C.sub.1-3 alkyl group; and one of the groups represented by

Medicaments for the treatment of nausea and vomiting

The invention relates to compounds of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, phenylC.sub.1-3 alkyl, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 or --SO.sub.2 R.sup.5 ;

Tricyclic ketones useful as HT.sub.3 -receptor antagonists

The invention relates to a process for the preparation of compounds of general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4)alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-(C.sub.1-3)alkyl group, and one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-phenyl-(C.sub.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.sub.1-6 alkyl group; or a salt or protected derivative thereof by cyclization of a compound of general formula (II) ##STR2## wherein X represents a hydrogen atom or a halogen atom and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, or a salt or a protected derivative thereof. The compounds of formula (I) are potent and selective antagonists at 'neuronal' 5-hydroxytryptamine receptors.

Process for preparing N-heterocyclic compounds

The invention relates to ketones of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## one of the groups represented by R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenyl C.sub.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.sub.1-6 alkyl group;

Tricyclic ketone derivatives as 5-HT antagonists

The invention relates to compounds of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the 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.sub.3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety, and nausea and vomiting.

Tetrahydro-imidazolylmethylcarbazolones and analogs thereof for treating

Tetrahydro carbazolone intermediates

The invention relates to compounds of formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-10 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, phenyl, or phenyl C.sub.1-3 alkyl, --CO.sub.2 R.sup.10, --COR.sup.10, --CONR.sup.10 R.sup.11 or --SO.sub.2 R.sup.10 (wherein R.sup.10 and R.sup.11, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenylC.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.10 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.10 or --SO.sub.2 R.sup.10);

Indole derivatives

The invention relates to the use of compounds of the general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycoalkyl-(C.sub.1-4) alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-C.sub.1-3 alkyl group, and one of the groups represented by

Method for treating nausea and vomiting

The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 represents a group CO.sub.2 R.sup.5, COR.sup.5, CONR.sup.5 R.sup.6 or SO.sub.2 R.sup.5 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenyl-(C.sub.1-4)alkyl group in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.5 does not represent a hydrogen atom when R.sup.1 represents a group CO.sub.2 R.sup.5 or SO.sub.2 R.sup.5);

Carbazole derivatives and their use as 5HT-induced antagonists

The invention relates to a process for the preparation of a compound of general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4)alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-(C.sub.1-3)alkyl group, and one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.1-3)alkyl group and each of the other two groups, which may be the same or different, represent a hydrogen atom or a C.sub.1-6 alkyl group; or a salt or protected derivative thereof, by cyclization of a compound of general formula (II) ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, or a salt or a protected derivative thereof. The compounds of formula (I) are potent and selective antagonists at 'neuronal' 5-hydroxytryptamine receptors.

Process for preparing tetrahydrocarbazolones

The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4)-alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-(C.sub.1-3)alkyl group; one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.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.sub.1-6 alkyl group; and X represents a halogen atom or a hydroxy, C.sub.1-4 alkoxy, phenyl-(C.sub.1-3)-alkoxy or C.sub.1-6 alkyl group or a group NR.sup.5 R.sup.6 or CONR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom or a C.sub.1-4 alkyl or C.sub.3-4 alkenyl group, or together with the nitrogen atom to which they are attached form a saturated 5 to 7 membered ring; 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.

Growing community of inventors

Ealing, United Kingdom

David C Humber