Imperial Chemical Industries Limited

National Research Development Corporation

Zeneca Limited

Ici Pharma

Peter R Marsham

Andrew John Barker

Leslie R Hughes

John Oldfield

Stephen J Pegg

Robert Hugh Bradbury

Frederic H Jung

David Huw Davies

Jean Bowler

David Charles Blakey

Edward D Brown

David S Thomson

Jean J Lohmann

Edward Raymond Walker

Georges Pasquet

Anthony Michael Slater

John Frederick Hennam

Laurent Francois Andre Hennequin

Francis Thomas Boyle

Robert I Dowell

David William Heaton

Laurent Francois Hennequin

Brian Robert Rabin

Antonio Tarragona-Fiol

Hendrikus Johannes Eggelte

Christopher John Taylorson

Antibody Directed Enzyme Prodrug Therapy (ADEPT) systems for use in cancer based on mutated carboxypeptidase B (CPB) enzymes. Enzyme conjugates for ADEPT are substantially non-immunogenic in humans comprising a targeting moiety (for example an antibody) capable of binding with a tumor associated antigen, the targeting moiety being linked to a mutated form of a CPB enzyme capable of converting a prodrug into an antineoplastic drug wherein the prodrug is not significantly convertible into antineoplastic drug in humans by natural unmutated enzyme. A preferred enzyme mutant is human pancreatic CPB comprising a Lys or Arg residue at position 253. Suitable mustard prodrugs are disclosed in the specification.

Chemical compounds

The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumour activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms;

6-substituted quinazolines processing anti-tumor activity

A cephalosporin derivative of the formula I: ##STR1## in which X is S, O, CH.sub.2 or SO, ##STR2## represents one of C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl or allyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.

Cephalosporin intermediates

Anti-tumor agents

The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms;

Quinazoline derivatives possessing anti-tumor activity

A cephalosporin derivative of the formula I: ##STR1## in which X is ##STR2## represents one of C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl or allyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.

Cephalosporin derivatives

The invention concerns novel esters of 4-(1-hydroxy-2-[(acylamino)alkylamino]ethyl)phenols of the formula: ##STR1## and salts thereof, wherein R.sup.1 and R.sup.2 are (3-5C)alkyl, R.sup.3 and R.sup.4 are hydrogen or methyl, A is a direct bond or methylene, and Q is various heteroaromatic containing groups. The esters possess topical anti-inflammatory properties and the invention provides pharmaceutical compositions containing the esters and processes for their chemical manufacture.

Anti-inflammatory esters of

Anti-inflammatory esters of 4-(1-hydroxy-2-[(acylamino)alkylamino]ethyl)

The disclosure relates to 9.beta.-aryloxy prostane derivatives, for example 16-(3-chlorophenoxy)-11.alpha.,15.alpha.-dihydroxy-16-methyl-9.beta.-pheno xy-18,19,20-trinor-5-cis,13-trans-prostadienoic acid, which possess high activity as abortifacients, cervical softeners, inducers of parturition or inhibitors of gastric acid production in mammals. These properties are typical of prostaglandin analogues of the E series, but chemically the new 9.beta.-aryloxy prostane derivatives are prostaglandin F series analogues and are therefore more stable than the E series analogues previously used for the above purposes. The new derivatives are manufactured by known analogy processes, and are formulated in conventional manner.

9-Aryloxy prostane derivatives

The disclosure relates to novel 15-(3-aryl- or 3-aralkyl-cyclobutyl, -cyclopentyl and -cyclohexyl)-.omega.-pentanor prostaglandin analogues, for example 9.alpha.,11.alpha.,15.alpha.-trihydroxy-15-(trans-3-phenylcyclobutyl)-16,1 7,18,19,20-pentanor-5-cis, 13-trans-prostadienoic acid, to pharmaceutical or veterinary compositions containing such a compound, and to a method of inducing luteolysis in animals by orally administering such a compound.

Prostane derivatives

The disclosure relates to novel 15-(3-aryl- or 3-aralkyl-cyclobutyl, -cyclopentyl and -cyclohexyl)-.omega.-pentanor prostaglandin analogues, for example 9.alpha.,11.alpha.,15.alpha.-trihydroxy-15-(trans-3-phenylcyclobutyl)-16,1 7,18,19,20-pentanor-5-cis,13-trans-prostadienoic acid, to pharmaceutical or veterinary compositions containing such a compound, and to a method of inducing luteolysis in animals by orally administering such a compound.

The disclosure relates to novel pentanor prostaglandin analogues, for example 15-(5-chloroindan-2-yl)-9.alpha.,11.alpha.,15-trihydroxy-16,17,18,19,20-pe ntanor-5-cis,13-trans-prostadienoic acid and 15-(5-chloroindan-2-yl)-11.alpha.,15-dihydroxy-9-oxo-16,17,18,19,20-pentan or-5-cis,13-trans-prostadienoic acid and the 1-ester and 1-alcohol derivatives thereof, to a process for their manufacture, to compositions containing them, and to their use in a method of inducing luteolysis.

Cyclopentane derivatives

The disclosure relates to novel pentanor prostaglandin analogues, for example 15-(5-chloroindan-2-yl)-9.alpha.,11.alpha.,15-trihydroxy-16,17,18,19,20-pe ntanor-5-cis, 13-trans-prostadienoic acid and 15-(5-chloroindan-2-yl)-11.alpha.,15-dihydroxy-9-oxo-16,17,18,19,20-pentan or-5-cis,13-trans-prostadienoic acid and the 1-ester and 1-alcohol derivatives thereof, to a process for their manufacture, to compositions containing them, and to their use in a method of inducing luteolysis.

Growing community of inventors

Poynton, United Kingdom

Peter R Marsham