Merrell Toraude Et Compagnie

Merrell Pharmaceuticals, Inc.

Merrell Dow Pharmaceuticals

Richardson-merrell Inc.

Other

The United States of America As Represented by the Department of Health

Aventis Pharma Limited

Eugene L Giroux

Paul J Schechter

Nellikunja J Prakash

Gary A Flynn

Douglas Wade Beight

Alan M Warshawsky

Philippe Bey

Edward D Daugs

Timothy Paul Burkholder

Joseph P Burkhart

Shujaath Mehdi

Daniel G Schirlin

John F French

Bernhard Neises

H Michael Kolb

Fritz E Gerhart, Deceased

Michel J Jung

Robert I Henkin

Fritz E Gerhart

Michael Kolb

Michael J Jung

Phillipe Bey

This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

Peptidase inhibitors

The present invention relates to certain novel mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and of ACE.

Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase

A method of reducing local hemorrhage and tissue necrosis resulting from the bite or sting of a venomous animal whereby an envenomated mammal is treated with a compound of the formula ##STR1## or a corresponding disulfide wherein n is 1, 2 or 3; Z is O, S or NH; R is H, a straight or branched chain lower alkyl group of from 1 to 4 carbon atoms, hydroxy, a straight or branched chain lower alkoxy group of from 1 to 4 carbon atoms, fluoro, chloro, bromo, iodo or trifluoromethyl; or a pharmaceutically acceptable salt thereof.

Snake bite therapy

A method of reducing local hemorrhage and tissue necrosis resulting from the bite or sting of a venomous animal whereby an envenomated mammal is treated with a compound of the formula: ##STR1## or a corresponding disulfide wherein n is 1, 2 or 3; Z is O, S or NH; R is H, a straight or branched chain lower alkyl group of from 1 to 4 carbon atoms, hydroxy, a straight or branched chain lower alkoxy group of from 1 to 4 carbon atoms, fluoro, chloro, bromo, iodo or trifluoromethyl; or a pharmaceutically acceptable salt thereof.

This invention relates to a novel method for treating hypertension, which comprises administering a compound of the formula: ##STR1## wherein Z is C.dbd.C, O, S or NH; R is hydrogen, methyl, ethyl, hydroxy, methoxy, ethoxy, chlorine, bromine, fluorine, iodine or trifluoromethyl; and n is 1, 2, or 3.

Use of .alpha.,.alpha.'-dithiobis-(.beta.-arylacrylic acid) derivatives

This invention relates to a novel method for enhancing zinc serum and tissue concentrations which comprises administering a compound of the formula: ##STR1## wherein Z is C.dbd.C, O, S, NH; R is hydrogen, methyl, ethyl, hydroxy, methoxy, ethoxy, chlorine, bromine, fluorine, iodine or trifluoromethyl; and n is 1, 2 or 3.

Use of .alpha.,.alpha.'-dithiobis(.beta.-arylacrylic acid) derivatives

This invention relates to a novel method for combatting heavy metal poisoning which comprises administering a compound of the formula: ##STR1## wherein Z is C.dbd.C, O, S, NH; R is hydrogen, methyl, ethyl, hydroxy, methoxy, ethoxy, chlorine, bromine, fluorine, iodine or trifluoromethyl; and n is 1, 2 or 3.

This invention relates to a novel method for combatting poisoning resulting from heavy metals which comprises administering a compound of the formula: ##STR1## wherein Z is C.dbd.C, O, S, NH; R is hydrogen, methyl, ethyl, hydroxy, methoxy, ethoxy, chlorine, bromine, fluorine, iodine or trifluoromethyl; and n is 1, 2 or 3.

Use of .alpha.-mercapto-.beta.-arylacrylic acid derivatives in heavy

This invention relates to a novel method for the treatment of hypertension which comprises administering a compound of the formula: ##STR1## wherein Z is C.dbd.C, O, S, NH; R is hydrogen, methyl, ethyl, hydroxy, methoxy, ethoxy, chlorine, bromine, fluorine, iodine or trifluoromethyl; and n is 1, 2 or 3.

Method of treating hypertension

Zinc serum and tissue levels are enhanced by therapeutic administration of certain .alpha.-mercapto-.beta.-aryl acrylic acids.

Enhancing zinc serum and tissue levels

A process for the purification of the active principle of the fruit of the plant Synsepalum dulcificum is disclosed. The process includes contacting the fruit with a suspension of polyvinyl pyrrolidone, followed by adsorption of the active principle by means of chromatography procedures. By following the process in accordance with the present invention, proteases and tannins are substantially completely eliminated from the final product. The active principle of this fruit, when prepared in accordance with the present invention, has been found to be particularly useful in controlling obesity in human beings.

Growing community of inventors

Cincinnati, OH, United States of America

Eugene L Giroux