Glaxo Group Limited

Smithkline Beecham Corporation

Nigel Stephen Watson

Chuen Chan

Henry Anderson Kelly

Robert John Young

Andrew McMurtrie Mason

Vipulkumar Kantibhai Patel

Gita Punjabhai Shah

Nigel Paul King

Stefan Senger

Julie Nicole Hamblin

Caroline Whitworth

Helen Elisabeth Weston

Alan D Borthwick

Barry C Ross

Savvas Kleanthous

Michael John Dawson

David Noble

Allan Baxter

Robert M Tait

Howard G Wildman

Michael V Hayes

Alan Shuttleworth

Panayiotis Alexandrou Procopiou

John David Harling

Matthew Campbell

Paul William Smith

Michael G Lester

Barrie E Kirk

Martin Pass

Philip C Dell 'Orco

Wendy Rebecca Irving

The present invention includes (E)-2-(5-Chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}ethenesulfonamide in substantially crystalline form, pharmaceutical formulations thereof, processes for preparing it, and its use in medicine, particularly use in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

Crystalline derivatives of (E)-2-(5-chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}ethenesulfonamide

The invention relates to compounds of formula (I) processes for their preparation, pharmaceutical compositions containing them and to their use in medicine, particularly use in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

Pyrrolidine derivatives as factor Xa inhibitors

The invention relates to compounds of formula (I): wherein substituents are as defined.

Pyrrolidine-2-ones as Factor Xa inhibitors

1-Phenyl-2-oxo-3-sulfonylamino-pyrrolidine derivatives and related compounds as factor Xa inhibitors for the treatment of acute vascular diseases

Pyrrolidine derivatives as factor XA inhibitors

The invention relates to compounds of formula (Ic) processes for their preparation, pharmaceutical compositions containing them and to their use in medicine, particularly use in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

Pyrrolidin-2-one derivatives as inhibitors of factor xa

3-sulfonylamino-pyrrolidine-2-one derivatives as inhibitors of factor Xa

Pyrrolidine derivatives as Factor Xa inhibitors

The invention relates to compounds of formula (I) pharmaceutical compositions containing the same as well as methods of treating patients suffering from a condition susceptible to amelioration by a Factor Xa inhibitor using the same. 

2-(3-sulfonylamino-2-oxopyrrolidin-1-yl)propanamides as factor xa inhibitors

Pyrrolidin-2-one derivatives as inhibitors of factor Xa

The invention relates to a novel class of amide derivatives which act as thrombin inhibitors as described by formula (I), where R,and R,, independently represent a group (a) or R,and R,together form a C,heterocycloalkyl or heterocycloalkenyl group which may be optionally substituted by C,alkyl, C,alkoxy, halogen, carboxylic acid or a C,carboxylic acid ester group; R,represents hydrogen, C,alkyl, halogen, or C,alkoxy; R,, R,and R,independently represent hydrogen, or halogen; R,represents hydrogen or C,alkyl; R,represents hydrogen, C,cycloalkyl, C,cycloalkenyl, C,heterocycloalkyl, C,heterocycloalkenyl, aryl or heteroaryl, which groups are optionally substituted by one or more groups selected from halogen, hydroxy, CN, C,alkyl, C,alkoxy, C,acyloxy, NR,R,, NHCOR,, NHSO,R,, COR,, CO,R,, CONR,R,, and SO,NHR,; X represents a bond, a C,alkyl chain, or a C,alkenyl chain, where one or two nitrogen, oxygen, or sulfur atoms may be optionally contained within each chain, and the chains are optionally substituted by one or more groups selected from halogen, hydroxy, CN, C,alkyl, C,alkoxy, C,acyloxy, NR,R,, NHCOR,, NHSO,R,, COR,, CO,R,, CONR,R,, and SO,NHR,; R,-R,represent hydrogen, C,alkyl, or R,and R,or R,and R,form a C,heterocycloalkyl ring, or R,additionally may represent trifluoromethyl; and pharmaceutically acceptable derivatives or solvates thereof, to processes for their preparation; and their use in the treatment of clinical conditions susceptible to amelioration by administration of a thrombin inhibitor.

Benzamide derivatives as thrombin inhibitors

Compounds are described of the formula ##STR1## wherein R.sub.1 represents a hydrogen atom, a hydroxyl group or a group selected from --OCOCH.dbd.CHCH(CH.sub.3)(CH.sub.2).sub.3 CH.sub.3, --OCOCH.dbd.CHC(CH.sub.3).dbd.CHCH(CH.sub.3)--CH.sub.2 CH.sub.3, or --OCO--X--CH.sub.2 CH(CH.sub.3)CH.sub.2 CH.sub.3 [where X is --CH.dbd.CHCH(CH.sub.3)--, --CH.sub.2 CH(OH)CH(CH.sub.3)--, --CH.dbd.CHC(OH)(CH.sub.3)--, --CH.sub.2 CH(OH)CH.sub.2 -- or --CH.sub.2 CH.sub.2 CH(CH.sub.3)--)]; R.sub.2 represents a hydrogen atom or a hydroxyl group; R.sub.3 represents a group selected from --C(.dbd.CH.sub.2)CH(OR.sub.7)CH(CH.sub.3)CH.sub.2 Ph (where R.sub.7 is a hydrogen atom or an acetyl group), --C(CH.sub.3).dbd.CHCH(CH.sub.2 R.sub.8)CH.sub.2 Ph (where R.sub.8 is a hydrogen or a hydroxyl group), --C(CH.sub.2 OH).dbd.CHCH(CH.sub.3)CH.sub.2 Ph, --C(.dbd.CH.sub.2)CH(OH)CH(CH.sub.2 OH)CH.sub.2 Ph, --C(.dbd.CH.sub.2)CH(NHCOCH.sub.3)CH(CH.sub.3)CH.sub.2 Ph, --C(CH.sub.2 NHCOCH.sub.3).dbd.CHCH(CH.sub.3)CH.sub.2 Ph or ##STR2## R.sub.4, R.sub.5 and R.sub.6 may each independently represent a hydrogen atom or a methyl group and salts thereof; with the proviso that when either of R.sub.1 and R.sub.2 represents a hydrogen atom R.sub.3 is a group selected from --C(.dbd.CH.sub.2)CH(OR.sub.7)CH(CH.sub.3)CH.sub.2 Ph and --C(CH.sub.3).dbd.CHCH(CH.sub.3)CH.sub.2 Ph and when both of R.sub.1 and R.sub.2 represent hydrogen atoms R.sub.3 represents --C(CH.sub.3).dbd.CHCH(CH.sub.3)CH.sub.2 Ph. These compounds inhibit the enzyme squalene synthase and/or are intermediates for the preparation of compounds which inhibit the enzyme squalene synthase. Compounds of the invention may be formulated for use in a variety of conditions where a lowering of the level of blood plasma cholesterol in animals would be beneficial and for use in combating fungal infections in animals.

Cyclic ketal derivatives

The invention is directed to a biologically pure culture of the microorganism Phoma sp. IMI 332962 or a mutant thereof.

Growing community of inventors

Stevenage, United Kingdom

Nigel Stephen Watson