Pfizer Corporation

John Steele

Kenneth Richardson

Mark Edward Bunnage

Kelvin Cooper

Michael J Fray

Charlotte Moira Norfor Allerton

Roger P Dickinson

Kevin Neil Dack

Robert John Maguire

David John Bull

Peter E Cross

Julian Blagg

Melvin Cooper

Compounds according to formula (I) wherein n is 0-3, Ris optionally substituted Calkyl, Calkenyl, or Calkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R, R, R, R, R, R, Rand Rare each independently selected from hydrogen and optionally substituted Calkyl, or Rand Rare an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition

3-(imidazolyl)-2-alkoxypropanoic acids

The present invention provides compounds of formula (I)as well as the use of such compounds in pharmaceutical compositions and methods of treatment. The compounds described herein represent a class of TAFIa inhibitors suitable for use in treating conditions such as thrombosis, atherosclerosis, adhesions, dermal scarring, cancer, fibrotic conditions, inflammatory diseases and those conditions which benefit from maintaining or enhancing bradykinin levels in the body.

Pharmaceuticals

Compounds according to formula (I) wherein n is 1-4, Ris optionally substituted Calkyl, Calkenyl, or Calkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R, R, R, R, R, Rand Rare each independently selected from hydrogen and optionally substituted Calkyl are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition.

3-(imidazolyl)-2-aminopropanoic acids

Compounds according to formula (I) wherein n is 1-4, R is optionally substituted C alkyl, C alkenyl, or C alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R , R , R , R , R , R and R are each independently selected from hydrogen and optionally substituted C alkyl are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition.

3-(Imidazolyl)-2-aminopropanoic acids

Compounds according to formula (I) wherein n is 0-3, R is optionally substituted C alkyl, C alkenyl, or C alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R , R , R , R , R , R , R and R are each independently selected from hydrogen and optionally substituted C alkyl, or R and R are an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition.

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

##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

Intermediates useful in the synthesis of dihydropyridine platelet activating factor antagonists of the formula ##STR1## where R is phenyl or substituted phenyl; R.sup.3 is lower alkyl; Y is 1,4-phenylene and X is 2-alkylimidazopyridyl.

Alkyl 2-benzylidene-4-(2-alkylimidazopyrid-1-yl) benzoylacetate esters

Platelet activating factor antagonists of formula (I): ##STR1## wherein R is phenyl or phenyl substituted by one or more substituents selected from nitro, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl(C.sub.1 -C.sub.4)alkoxy, fluoro(C.sub.1 -C.sub.4)alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphonyl, hydroxy, trifluoromethyl and cyano, or is phenyl fused to a dioxole ring;

Platelet activating factor antagonists

Intermediates useful in the synthesis of dihydropyridine platelet activating factor antagonists of the formula ##STR1## where R is phenyl or substituted phenyl; R.sup.3 is lower alkyl; Y is 1,4-phenylene and X is a benzimidazol-1-yl.

Alkyl 2-benzylidene-4-(benzimidazol-1-yl) benzoylacetate esters as

The invention provides compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R is phenyl substituted by halo;

1,4-dihydropyridine derivatives

Platelet activating factor antagonists of formula (I): ##STR1## wherein R is phenyl or phenyl substituted by one or more substituents selected from nitro, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl (C.sub.1 -C.sub.4) alkoxy, fluoro (C.sub.1 -C.sub.4) alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphonyl, hydroxy, trifluoromethyl and cyano, or is phenyl fused to a dioxole ring;

4-Aryl-3-alkoxycarbonyl-6-methyl-5-carbamyl-2-triazolylalkoxymethyl-1,4-dih yd ropyridines as anti-allergic and anti-inflammatory agents.

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Sandwich, United Kingdom

John Steele