Merck + Co., Inc.

Suresh K Balani

Byron H Arison

Harri G Ramjit

Laura R Kauffman

Anthony D Theoharides

Philip E Sanderson

Steven M Pitzenberger

William J Greenlee

Matthew G Stanton

Clarence S Rooney

Theresa M Williams

Walfred S Saari

William C Lumma, Jr

John S Wai

Wayne J Thompson

Joel R Huff

Russell B Lingham

Terrence M Ciccarone

Jacob M Hoffman, Jr

Laszlo R Treiber

Mark E Goldman

Georgette Dezeny

Lawrence F Colwell, Jr

Michael S Schwartz

Anthony Y Lu

Anthony D Theoharides, Deceased

Claude Dufresne

Thomas A Baillie

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: ##STR1## wherein ##STR2##

Pyrazinone thrombin inhibitors

Compounds of Formula I: ##STR1## are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.

Quinoline leukotriene antagonists

Novel indole compounds inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Inhibitors of HIV reverse transcriptase

Incubation of ##STR1## with a preparation from mammalian organ yields as biotransformation product the compound 3-[2-(benzoxazol-2-yl)ethyl]-5-(1-hydroxyethyl)-6-methyl-2-(1H)-pyridinone . This product is useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

Preparation of

Incubation of ##STR1## with a preparation from mammalian organ yields as biotransformation products the 5-(1-hydroxy)ethyl pyridinone analog as well as the 5-(1-hydroxy)ethyl pyridyl and the 5-(2-hydroxy)ethyl pyridyl derivatives.

Method of hydroxylating

Incubation of 3-[2-benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-2-(1H)-pyridinone ##STR1## with a preparation from mammalian organ yields as biotransformation product the 6-hydroxymethyl analog. This product is useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

Incubation of 3-[(4,7-dichlorobenzoxazol-2-yl)methyl]amino-5-ethyl-6-methyl-2-(1H)-pyrid inone ##STR1## with a preparation from mammalian organ yields as biotransformation products the 5-(1-hydroxy)ethyl and 6-hydroxymethyl analogs. These products are useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

A dipeptide isostere is the biotransformed product after incubation with a culture of Streptomyces. It inhibits HIV protease, and is useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Synthesis of protease inhibitor

Novel dipeptide isosteres are the biotransformed products after incubation with rat liver slices. They inhibit HIV protease, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts (when appropriate), pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Method of preparing HIV protease inhibitors

Incubation of ##STR1## with a preparation from mammalian organ yields as biotransformation products the 6-hydroxymethyl and 5-(1-hydroxy)ethyl anologs. These products are useful in the prevention or treatment of infection by HIV and the treatment of AIDS.

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Hatfield, PA, United States of America

Suresh K Balani