Merck + Co., Inc.

Aventis Pharmaceuticals Inc.

Rhone-Poulenc Rorer Pharmaceuticals Inc.

Matthew M Morrissette

Terry A Lyle

Peter D Williams

Donnette D Staas

Joseph M Salvino

Philip E Sanderson

Lekhanh O Tran

Harold G Selnick

Matthew G Stanton

Stevan Wakefield Djuric

Craig Alan Coburn

Bruce D Dorsey

Christopher J Burns

James C Barrow

John S Wai

Philippe G Nantermet

Anthony C Scotese

Kent W Neuenschwander

George C Morton

Robert D Groneberg

Thorsten E Fisher

Richard F Labaudiniere

Adel M Naylor-Olsen

Catherine M Wiscount

Kenneth E Rittle

Liang Ma

Kenneth J Stauffer

John W Ullrich

Christopher Hulme

Helen J Mason

Marie-Pierre Cherrier

Steven M Condon

Gerald M McGeehan

Compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein Z, R, R, R, R, R, R, R, Rand Rare defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

HIV integrase inhibitors

Thrombin inhibitors

A method for preparing a N-&lsqb;(aliphatic or aromatic)carbonyl)&rsqb;-2-aminoacetamide compound, and for preparing a cyclized compound therefrom, as well as novel resin bound intermediate compounds that are useful for preparing such compounds.

Methods for preparing N-&lsqb;(aliphatic or aromatic)carbonyl)&rsqb;-2-aminoaetamide compounds and for cyclizing such compounds

This invention is directed to compounds of formula I: ##STR1## wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. Compounds within the scope of the present invention may also inhibit an MMP, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting MMPs, such disease states involve tissue breakdown and those associated with a physiologically detrimental excess of TNF. The present invention is therefore also directed to the pharmaceutical use of the compounds, pharmaceutical compositions containing the compounds, intermediates leading thereto and methods for the preparation of the compounds and their intermediates.

Substituted (aryl, heteroaryl, arylmethyl or heteroarylmethyl)

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Pottstown, PA, United States of America

Matthew M Morrissette