Pfizer Corporation

Warner-lambert Company

Roger P Dickinson

Peter E Cross

Kevin Neil Dack

David James Rawson

Kim James

John Steele

Kenneth Richardson

Christopher Gordon Barber

Geoffrey N Thomas

John E Arrowsmith

John Edward Kemp

Simon F Campbell

Alan Daniel Brown

Martin James Wythes

Ian T Barnish

Michael J Fray

Paul Vincent Fish

David Ellis

Andrew Michael Derrick

Stephen Challenger

Yousef Hajikarimian

2-pyridinylguanidine urokinase inhibitors

Indole derivatives useful as endothelin receptor antagonists

Matrix metalloprotease inhibitors

Isoquinolines as urokinase inhibitors

The invention provides S-(&plus;)-3-&lcub;1-(1,3-benzodioxol-5-yl)-2-&lsqb;(2-methoxy-4-methylphenyl)sulfonylamino&rsqb;-2-oxoethyl&rcub;-1-methyl-1H-indole-6-carboxylic acid, which is substantially free from its (R)-(&minus;)-enantiomer, and pharmaceutically acceptable derivatives thereof. The compounds are useful in the treatment of inter alia acute renal failure, restenosis and pulmonary hypertension.

Indole derivatives useful in therapy

##STR1## Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R.sup.1 and R.sup.2 are optional substituents and independently represent C.sub.1-6 alkyl, C.sub.2-6 alkenyl optionally substituted by CO.sub.2 H or CO.sub.2 (C.sub.1-6 alkyl, C.sub.2-6 alkynyl, halogen, C.sub.1-3 perfluoroalkyl, (CH.sub.2).sub.m Ar.sup.1, (CH.sub.2).sub.m Het.sup.1, (CH.sub.2).sub.m CONR.sup.7 R.sup.8, (CH.sub.2).sub.m CO.sub.2 R.sup.8, O(CH.sub.2).sub.q CO.sub.2 R.sup.8, (CH.sub.2).sub.m COR.sup.8, (CH.sub.2).sub.m OR.sup.8, O(CH.sub.2).sub.p OR.sup.8, (CH.sub.2).sub.m NR.sup.7 R.sup.8, CO.sub.2 (CH.sub.2).sub.q NR.sup.7 R.sup.8, (CH.sub.2).sub.m CN, S(O).sub.n R.sup.8, SO.sub.2 NR.sup.7 R.sup.8, CONH(CH.sub.2).sub.m Ar.sup.1 or CONH(CH.sub.2).sub.m Het.sup.1 ; R.sup.3 represents H, C.sub.1-6 alkyl, (CH.sub.2).sub.p CONR.sup.9 R.sup.10, SO.sub.2 R.sup.10, SO.sub.2 NR.sup.9 R.sup.10, (CH.sub.2).sub.m COR.sup.10, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.m CONR.sup.9 R.sup.10, (CH.sub.2).sub.m CO.sub.2 R.sup.10, (CH.sub.2).sub.p CN, (CH.sub.2).sub.p R.sup.10 or (CH.sub.2).sub.p OR.sup.10 ; R.sup.4 represents H or C.sub.1-6 alkyl; R.sup.5 represents H or OH; R.sup.6 represents phenyl optionally fused to a heterocylic ring, the group as a whole being optionally substituted; R.sup.7-10 are fully defined herein and may independently represent Ar.sup.2 or Het.sup.2 ; Z represents CO.sub.2 H, CONH(tetrazol-5-yl), CONHSO.sub.2 O(C.sub.1-4 alkyl), CO.sub.2 Ar.sup.3, CO.sub.2 (C.sub.1-6 alkyl), tetrazol-5-yl, CONHSO.sub.2 Ar.sup.3, CONHSO.sub.2 (CH.sub.2).sub.q Ar.sup.3 or CONHSO.sub.2 (C.sub.1-6 alkyl); Ar.sup.1-3 independently represent phenyl, naphthyl, or an aromatic heterocycle, which groups are optionally fused and optionally substituted; and Het.sup.1 and Het.sup.2 independently represent a non-aromatic heterocycle which is optionally substituted; are useful in the treatment of restenosis, renal failure and pulmonary hypertension.

Compounds of formula I, ##STR1## wherein X represents O or S(O).sub.m ;

Benzothiophene derivatives useful in therapy

Indole derivatives thromboxane A2 antagonists

Compounds of formula: ##STR1## or a biolabile ester thereof, or a pharmaceutically acceptable salt of either, wherein

Pyridine- and imidazole-derived agents for cardiovascular diseases

Benzenealkanoic acids for cardiovascular diseases

Indole derivatives as 5-HT.sub.1 -like agonists

##STR1## Compounds of formula (I) or a biolabile ester thereof, or a pharmaceutically acceptable salt of either, wherein R.sup.l, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from H or C.sub.1 -C.sub.4 alkyl; R.sup.5 is (CH.sub.2).sub.m SO.sub.2 R.sup.6, (CH.sub.2).sub.m NHSO.sub.2 R.sup.6 or (CH.sub.2).sub.m NHCOR.sup.7 ; R.sup.6 and R.sup.7 are C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl(CH.sub.2).sub.n, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.n, aryl(CH.sub.2).sub.n or heteroaryl(CH.sub.2).sub.n ; or R.sup.6 is NR.sup.8 R.sup.9 ; R.sup.8 is H or C.sub.1 -C.sup.4 alkyl; R.sup.9 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.n, aryl(CH.sub.2).sub.n or heteroaryl(CH.sub.2).sub.n ; or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring which may optionally incorporate a carbon-carbon double bond or a further hetero atom linkage selected from O, S, NH, N(C.sub.1 -C.sub.4 alkyl) and N(C.sub.1 -C.sub.5 alkanoyl), and which may optionally be substituted with one to three substituents each independently selected from C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.4 alkoxy, and which may optionally be benzo-fused; X is CH.sub.2, CHCH.sub.3, C(OH)CH.sub.3, C.dbd.CH.sub.2 or O; m is 0 or 1; n is 0, 1, 2 or 3; and Het is 3- or 4-pyridyl or 1-imidazolyl; with the proviso that when Het is 1-imidazolyl then X is CH.sub.2 or CHCH.sub.3, are combined thromboxane A.sub.2 synthetase inhibitors and thromboxane A.sub.2 /endoperoxide antagonists of utility in the treatment of disease conditions in which thromboxane A.sub.2 is a causative agent.

Pyridine derived agents for cardiovascular diseases

Growing community of inventors

Dover, United Kingdom

Roger P Dickinson