John Wyeth Brother, Limited

Alan C White

Ian A Cliffe

Robin G Shepherd

Edwin T Edington

Robin Michael Black

Richard S Todd

Howard L Mansell

John Frederick Cavalla

Terence J Ward

Barry John Langham

John F White

Michael C Minchin

Gerald Bradley

Anderson D Ifill

Allan Fletcher

Graham John Warrellow

Stanley Charles Bell

John Leheup Archibald

Michael G Wyllie

Christopher Ian Brightwell

Brian John Bushell

Mark A Ashwell

Richard Arthur Franklin

Robert F Sugden

Michael M Hann

Selective 5-HT.sub.1A antagonists radiolabelled with .sup.3 H or .sup.11 C are radiolabelled ligands useful, for example, in pharmacological screening procedures and in positron emission tomography (PET) studies.

5-HT.sub.1A ligands

Treatment of cognitive disorders with piperazine derivatives

Piperazine derivatives as 5-HT.sub.1A ligands

Piperazine derivatives

Amide derivatives

Piperazine derivatives of formula I ##STR1## and their pharmaceutically acceptable acid addition salts are 5-HT.sub.1A binding agents, particularly 5-HT.sub.1A antagonists and may be used, for example, as anxiolytics. In the formula R is hydrogen or one or two lower alkyl groups, R.sup.1 is a mono of bicyclic aryl or heteroaryl radical, R.sup.2 is aryl and A is a C.sub.2-5 alkylene chain optionally substituted by lower alkyl.

##STR1## where A is an alkylene chain of 1 or 2 carbon atoms optionally substituted by one or more lower alkyl groups, R is hydrogen or lower alkyl, R.sup.1 is a mono or bicyclic aryl or a heteroaryl radical, R.sup.2 is an aryl radical, a heteroaryl radical, or an aryl-or heteroaryl-lower alkyl radical, R.sup.3 is hydrogen, lower alkyl or aryl and R.sup.4 is hydrogen, lower alkyl, cycloalkyl, cycloalkyl(lower)alkyl, aryl, or aryl(lower)alkyl or R.sup.3 and R.sup.4 together with the nitrogen atom to which they are both attached represent a saturated heterocyclic ring which may contain a further hetero atom and the dotted line represents a single or double bond, the hydrogen atoms shown in brackets being present when the dotted line represents a single bond and their pharmaceutically acceptable acid addition salts are 5-HT.sub.1A binding agents which may be used, for example, for the treatment of CNS disorders such as anxiety.

The invention concerns a method for treating pain and/or CNS disorders characterized in that the method uses a compound which acts selectively as an antagonist of gamma aminobutyric acid (GABA) at GABA autoreceptors relative to GABA.sub.A receptors.

Method of treatment and heterocyclic compounds used therein

Pyridine derivatives of formula ##STR1## their heteroaromatic N-oxides and their pharmaceutically acceptable acid addition salts are disclosed. In the formula z is 0, 1 and 2; R is hydrogen, hydroxy, lower alkyl, lower alkoxy, halogen, trifluoromethyl, nitro, amino, (lower)alkylamino or di(lower)alkylamino; R.sup.1 is hydrogen or lower alkyl; R.sup.2 is --(CH.sub.2).sub.n --R.sup.3 or --CH.sub.2 --CH.dbd.CH--(CH.sub.2).sub.m --R.sup.3 or --CH.sub.2.C.tbd.C.(CH.sub.2).sub.m --R.sup.3 where n is 1 to 6, and m is 0 to 3; and R.sup.3 is a ring of formula ##STR2## The compounds exhibit activity as 5-HT.sub.1A agonists, antagonists or partial agonists and are used for the treatment of CNS disorders, e.g. anxiety, as antihypertensives and in treating anorexia.

N-(2,3-dihydro-1,4-benzodioxinyl)-N-substituted aminopyrido-fused

Azetidine derivatives of formula ##STR1## and their pharmaceutically acceptable acid addition salts are disclosed. In the formula R is hydrogen or one or more specified substituents. The compounds have hypotensive activity. Some are also 5-HT.sub.1A agonists.

Azetidine derivatives and hypotensive compositions thereof

Pharmaceutical tetrahydroisoquinolines

Pyridine derivatives of formula ##STR1## their heteroaromatic N-oxides and their pharmaceutically acceptable acid addition salts are disclosed. In the formula z is 0, 1 and 2 and R, R.sup.1, R.sup.2 and R.sup.2 have specified meanings. The compounds exhibit activity as 5-HT.sub.1A agonists, antagonists or partial agonists and are useful for the treatment of CNS disorders e.g. anxiety, as antihypertensives and in treating anorexia.

Pyridine derivatives

Pyrimidoindoles of formula (I) ##STR1## and their pharmaceutically acceptable acid addition salts, wherein R represents lower alkyl a mono- or bicyclic aryl radical or a group of mormula R.sup.3 O--B--[where R.sup.3 O is (lower)alkoxy,aryl(lower)alkoxy or hydroxy and B is a lower alkylene chain optionally containing one double or triple bond], R.sup.1 and R.sup.2 which may be the same or different each represent hydrogen, hydroxyl, lower alkyl, lower alkoxy, halo(lower)alkyl, halogen, amino or mono- or di(lower) alkylamino and A, together with the carbon atom to which it is attached, represents 5, 6 or 7 membered saturated carbocyclic or heterocyclic ring, are useful as hypoglyceamics.

Hypoglycemic

Compounds of formula ##STR1## wherein A represents a lower alkylene chain optionally containing one double or triple bond, RO represents (lower)alkoxy, aryl(lower)alkoxy, hydroxy or protected hydroxy, R.sup.1 and R.sup.2 which may be the same or different each represent hydrogen, hydroxyl, lower alkyl, lower alkoxy, halo(lower)alkyl, halogen, amino or mono- or di(lower)alkylamino and R.sup.3 and R.sup.4 each independently represent hydrogen or lower alkyl and their pharmaceutically acceptable acid addition salts are useful as hypoglycaemics or as intermediates for hypoglycaemics.

Pyrimidoindoles useful as hypoglycaemics

The invention concerns thienoquinolizines of general formula (I) ##STR1## and their pharmaceutically acceptable acid addition salts. In the formula R.sup.1 is hydrogen or lower alkyl and R.sup.2 is lower alkyl, halo(lower)alkyl, --A--NR.sup.3 R.sup.4 [where A represents a direct bond between the S and N atoms or a lower alkylene group having 1 to 3 carbon atoms in the chain between the S and N atoms and R.sup.3 and R.sup.4 each independently represent hydrogen, lower alkyl, aryl or aryl(lower)alkyl or together with the nitrogen atom to which they are attached represent a five or six membered heterocyclic ring], aryl or a heterocyclic radical or R.sup.1 is --A.sup.1 NR.sup.5.SO.sub.2 R.sup.6 [where A.sup.1 is a lower alkylene group having 1 to 3 carbon atoms in the chain between the two N atoms, R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl, halo(lower)alkyl or aryl] and R.sup.2 is lower alkyl, halo(lower)alkyl or aryl. The compounds possess .alpha..sub.2 -adrenoceptor antagonistic activity in warm blooded animals.

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Windsor, United Kingdom

Alan C White