Glaxo Group Limited

Glaxo Wellcome Inc.

Peter C North

Alexander W Oxford

Ian H Coates

David J Cavalla

David E Bays

Michael B Tyers

Martin Redpath Johnson

Thomas Miller

Anthony D Baxter

Kevin Ian Hammond

Alan Naylor

Harry Finch

Lawrence H Lunts

Barry J Price

Paul John Beswick

Malcolm Clive Carter

Ian F Skidmore

Ian B Campbell

Frank Ellis

Keith Mills

Nigel Robert Oakley

Derek J Black

John W Whitehead

Steven J Cooper

Sjoerd N Wadman

Terence Aaron Panchal

Simon Charles Dolan

Jason William Cooke

The invention provides a process for the preparation of a compound of general formula (I):

Process for the preparation of lactam derivatives

Benzofurans and benzopyrans as chronobiological agents

Indoline derivatives, method of preparation and use

Benzofuran derivatives as 5-HT.sub.1 -like receptor antagonists

Indolyl compounds and their use in treatment of cephalic pain

The invention relates to tricyclic lactams of the general formula (I) ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## and 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, phenyl C.sub.1-3 alkyl, phenylmethoxymethyl, phenoxyethyl or phenoxymethyl,

Tetrahydro-1H-pyrido[4,3-b]indol-1-one derivatives

The invention relates to the use of compounds of the general formula (I) ##STR1## and physiologically acceptable salts and solvates thereof, in which Im represents an imidazolyl group of formula: ##STR2## and 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, phenylmethoxymethyl, phenoxyethyl, phenoxymethyl, --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 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.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);

Medicaments

The invention relates to the use of compounds of formula (I) ##STR1## wherein Im represents an imidazolyl group of formula: ##STR2## and 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, phenylmethoxymethyl, phenoxyethyl, phenoxymethyl, --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 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.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);

The invention relates to the use of a compound which acts as an antagonist of 5-HT at 5-HT.sub.3 receptors in the treatment of autism or another disorder originating in childhood in which there is mental retardation.

5-HT.sub.3 receptor antagonists for the treatment of autism

The invention relates to a process for the preparation of a compound of formula (I) ##STR1## wherein R represent a hydrogen atom or a methyl or ethyl group, which comprises cyclising a compound of formul (IV) ##STR2## Where R represents a hydrogen atom, the compound of formula (IV) may optionally be alkylated to produce a compound in whcich R is methyl or ethyl. The compound of formula (I) is useful as an intermediate in the preparation of 2,3,4,5-tetrahydro-2-[(imidazol-4(or 5)-yl)methyl]-1H-pyrido[4,3-b]indol-1-ones having 5-HT.sub.3 antagonist activity.

The invention provides potent and selective antagonists of 5-HT at 5-HT.sub.3 receptors which are tricyclic lactams of the formula (I) ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## and 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 ;

Lactam derivatives

The invention relates to imidazole derivatives of the general formula (I) ##STR1## wherein Im represents an imidazolyl group of formula: ##STR2## A represents the group CH or a nitrogen atom; R.sup.1 and R.sup.2, which may be the same or different, and may be attached to either the same or different fused rings of the naphthalene moiety, each represents a hydrogen atom, a halogen atom, or a hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 alkyl or C.sub.1-4 alkylthio group, and one of R.sup.1 and R.sup.2 may also represent a group --NR.sup.3 R.sup.4 (wherein R.sup.3 and R.sup.4, which may be the same or different, each represents a hydrogen atom or a C.sub.1-4 alkyl group, or together with the nitrogen atom to which they are attached form a saturated 5 to 7 membered ring);

Imidazole derivatives

The invention provides amide derivatives of the general formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom or a C.sub.1-6 alkyl group; Y represents a group --(CH.sub.2).sub.m --, where m represents 2, 3 or 4 or a group --X(CH.sub.2).sub.p, where p represents 2 or 3, X represents an oxygen or a sulphur atom or a group NR.sup.5, where R.sup.5 is a C.sub.1-6 alkyl group, and X is attached to the benzene ring moiety of the molecule; and Im represents an imidazolyl group of the formula: ##STR2## wherein 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.3-6 alkenyl, phenyl or phenylC.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 physiologically acceptable salts and solvates thereof. The compounds of formula (I) are potent and selective antagonists of 5-hydroxytryptamine at 5-HT.sub.3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety and nausea and vomiting.

5,6-dihydro-N-[(imidazol-4(or

The present invention provides ketones of the general formula (I): ##STR1## and physiologically acceptable salts and solvates thereof, wherein R.sup.1 and R.sup.2, which may be the same or different, each represents a hydrogen atom or a C.sub.1-6 alkyl group; Im represents an imidazolyl group of formula: ##STR2## wherein one of the groups represented by R.sup.3, R.sup.4 and R.sup.5 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.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

Ketone derivatives

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Royston, United Kingdom

Peter C North