E.i. Dupont De Nemours and Company

The Dupont Merck Pharmaceutical Company

John J Duncia

David J Carini

Pancras C Wong

Andrew T Chiu

Gregory J Wells

Joseph B Santella

Paul E Aldrich

Michael Ernest Pierce

Victor J De Noble

Richard Eric Olson

Mimi Lifen Quan

William Henry Miller

John Wityak

Robert J Ardecky

Patricia C Weber

Gregory James Pacofsky

Eugene Cruz Amparo

Mary K VanAtten

Carol L Ensinger

Ruth Richmond Wexler

Victor J DeNoble

Petrus B Timmermans

Greogry J Wells

Joseph Basil Santella, Iii

Sung-Eun Yoo

Carini, David J

Novel boronic acid and ester and carboxyl-modified amino acid compounds of the Formula I, which are inhibitors of trypsin-like enzymes, are disclosed :

Boronic acid and ester inhibitors of thrombin

Novel substituted imidazoles of Formula (I), which are useful as angiotensin II antagonists, are disclosed: ##STR1##

Imidazole 5-position substituted angiotensin II antagonists

Novel substituted imidazoles of Formula (III), which are useful as angiotensin-II antagonists, are disclosed: ##STR1## These compounds, exemplified by the compound 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1,1'-biphenyl)-4-yl)me thyl)-5-[2-(N-butyryl-N-pyridin-3-ylamino) ethylcarbonyl]-4-ethyl-2-propyl-1H-imidazole, are useful as antihypertensive agents.

Novel heterocycle substituted azocycloalkane benzylimidazoles of Formula (I), which are useful as angiotensin-II antagonists, are disclosed: ##STR1##

Angiotension-II receptor blocking, azacycloalkyl or azacycloalkenyl

Substituted imidazoles such as ##STR1## are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.

Angiotensin II receptor blocking imidazoles

Novel substituted dibenzobicyclo[2.2.2]octanes of formula I, which are useful as angiotensin II antagonists, are disclosed: ##STR1##

Dibenzobicyclo(2.2.2) octane angiotensin II antagonists

Substituted pyrazoles such as ##STR1## and their pharmaceutically suitable salts are useful as antihypertensive agents and for treatment of congestive heart failure.

Substituted pyrazole angiotensin II antagonists

Substituted imidazoles such as ##STR1## which are useful as angiotensin II receptor inhibitors. These compounds have activity in treating hypertension and congestive heart failure.

Fused aryl substituted imidazole angiotensin II receptor inhibitors

Substituted imidazoles such as 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxy methyl)imidazole and 2-butyl-4-chloro-1-[(2'-carboxybiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imi dazole and pharmaceutically acceptable salts thereof are useful for treating chronic renal failure, mediated by angiotensin-II.

Treatment of chronic renal failure with imidazole angiotensin-II

This invention includes substituted pyrroles, pyrazoles and triazoles, processes for their preparation, pharmaceutical compositions containing them, and their use as antihypertensive agents, and as a treatment for congestive heart failure in mammals. The heterocyclic compounds of the invention have the structural formula (I) ##STR1## or pharmaceutically suitable salts thereof.

Substituted 1,2,3 triazole angiotensin II antagonists

Imidazole compounds such as 5-[4-(3-(N-isopropylamino)hydroxypropoxy)indole-2-carboxamidomethyl]-2-n-b utyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-chloroimidazole and their pharmaceutically suitable salts are useful for treating central nervous system disorders, such as cognitive and learning disorders, mediated by angiotensin-II.

Treatment of central nervous disorders with imidazole compounds

4,5,6,7-Tetrahydro-1H-imidazo[4,5-c]pyridine derivatives such as 1-(4-amino-3-methylphenyl) methyl-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-car boxylic acid are useful for treatment of CNS disorders, such as cognitive and learning disorders, mediated by angiotensin-II.

Specific inhibition of angiotensin-II binding to angiotensin-II receptor

Method and composition for preventing NSAID-induced renal failure

Substituted pyrazole, pyrrole and triazole angiotensin-II-1 receptor antagonists and pharmaceutically acceptable salts thereof are useful for treating central nervous system disorders, such as cognitive and learning disorders, mediated by angiotensin-II.

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Newark, DE, United States of America

John J Duncia