The Dow Chemical Company

Merrell Dow Pharmaceuticals

Merrell Pharmaceuticals, Inc.

Hoechst Marion Roussel

Aventis Pharmaceuticals Inc.

Robert J Broersma

James R McCarthy

Donald Paul Matthews

Gayle A Spittka

Jeffrey Paul Whitten

Joseph E Dunbar

Louis E Begin

Thomas M Bargar

Bernhard Neises

George D Dickerson

Axel Ganzhorn

John L Krstenansky

Celine Tarnus

Charlotte L Barney

Norton P Peet

Joseph P Burkhart

Lawrence C Creemer

Thomas J Owen

J Anthony Malikayl

C Eline Tarnus

James R Mccarthy

J Antony Malikayl

This invention relates to polyfluoroalkyl tryptophan tripeptides and to compositions containing them. The compounds are highly selective thrombin inhibitors which provide anticoagulant effects useful in the treatment of thrombin conditions and in preventing the coagulation of stored whole blood and blood products.

Polyfluoroalkyl tryptophan tripeptide thrombin inhibitors

Novel compounds which contain a thrombin catalytic-site inhibitor coupled with an anion binding exosite associating moiety via an RGD-X bridging sequence are trifunctional anticoagulants useful in treating venous or arterial thrombotic conditions.

Trifunctional antithrombin and antiplatelet peptides

This invention relates to peptide derivatives which are useful anticoagulant agents.

Analogs of hirudin having anti-platelet activity

This invention relates to novel polyfluorinated alkyl derivatives of certain tripeptides, to the methods for their preparation, the intermediates therefore, to their use in inhibiting thrombin and lung tryptase and in their end-use application as anti-coagulants useful in treating thrombophlebitis and coronary thrombosis and in the treatment of asthma.

Thrombin inhibitors

Polyfluorinated tripeptide thrombin inhibitors

Imidazole-2-thione derivatives useful as antihypertensive agents are described herein. The compounds are obtained by cyclization of an appropriate open-chain compound such as an appropriately substituted thiourea.

Thione dopamine beta hydroxylase inhibitors

The present invention relates to allenyl amines, more specifically, .beta.-ethenylidene(substituted) ethanamines, possessing antihypertensive activity, and having the general formula ##STR1## wherein n is the integer 0, 1 or 2; each X independently is a substituent selected from the group consisting of loweralkyl, halo, --O--(loweralkyl), --S--(loweralkyl), --SO--(loweralkyl), --SO.sub.2 --(loweralkyl), CO.sub.2 R and CH.sub.2 OR, wherein R is loweralkyl and each loweralkyl group is from 1 to about 6 carbon atoms, or the pharmaceutically-acceptable addition salts thereof. These compounds are prepared by a novel reaction of a protected N,N-bis(trimethylsilyl)-4-methoxy-2-butynylamine compound with a metallo-organic compound, with subsequent removal of the silyl protecting groups to provide the desired compound.

Allenyl amines

Novel thione dopamine beta hydroxylase inhibitors

This invention relates to novel aminoalkyl substituted heterocyclic sulfur compounds which are useful as antihypertensive agents.

Novel aminoalkyl-substituted heterocyclic sulfur compounds

The present invention relates to compounds which are allenyl amines, more specifically, .beta.-ethenylidene-(substituted)ethanamines, possessing antihypertensive activity. They are prepared by a noval reaction of a protected N,N-bis(trimethylsilyl)-4-methoxy-2-butynylamine compound with a metallo-organic compound, with subsequent removal of the silyl protecting groups to provide the desired compound.

1,2-Disubstituted imidazoles useful as antihypertensive agents are described herein. The compounds are obtained from the appropriate 1-substituted imidazole which can be reacted with methyl oxalyl chloride to give the oxalyl derivative or it can be reacted with cyanogen chloride to give the 2-carbonitrile which can then be converted to the other derivatives desired.

Novel imidazole dopamine beta hydroxylase inhibitors

Method for inhibiting the sickling of sickle erythrocytes in blood by contacting the sickle erythrocytes with a compound of the formula: ##STR1## or a pharmaceutically-acceptable salt thereof, wherein X represents sulfur, oxygen or imino; R.sub.m represents chloro, bromo, fluoro or iodo; and R.sub.p represents chloro, bromo, fluoro, iodo, hydroxy, amino or alkyl.

Method of inhibiting sickling of sickle erythrocytes using

Method for inhibiting the sickling of sickle erythrocytes in blood by contacting the sickle erythrocytes with a compound of the formula: ##STR1## or a pharmaceutically-acceptable salt thereof wherein X represents sulfur, oxygen or imino; and R.sub.m and R.sub.p each independently represent hydrogen, cyano, nitro, alkylthio, alkylsulfinyl, alkylsulfonyl, alkyl or trifluoromethyl.

Method of inhibiting sickling of sickle erythrocytes

Method for inhibiting the sickling of sickle erythrocytes in blood by contacting the sickle erythrocytes with a compound of the formula: ##STR1## or a pharmaceutically-acceptable salt thereof, wherein R.sub.m represents hydrogen or alkyl; and R.sub.p represents chloro, bromo, fluoro or iodo.

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Noblesville, IN, United States of America

Robert J Broersma