Merck + Co., Inc.

Byron H Arison

Shieh-Shung T Chen

Linda S Wicker

Edward S Inamine

Raymond F White

Brian R Petuch

Laszlo R Treiber

John G MacConnell

Georgette Dezeny

George M Garrity

Marvin D Schulman

Lawrence F Colwell, Jr

Patrick J Doherty

Thomas R Beattie

Leeyuan Huang

Ali Shafiee

Suresh K Balani

Francis J Dumont

Matthew J Wyvratt

Michael H Fisher

Hyun O Ok

Russell B Lingham

Louis Kaplan

George A Doss

Carolyn L Ruby

Randall R Miller

John Howard Hutchinson

Mark E Duggan

Wasyl Halczenko

Richard L Monaghan

Wayne J Thompson

Robert T Goegelman

Gregory D Berger

Michael D Greenspan

Kevin M Byrne

Vincent P Gullo

Brian Heimbuch

Magda M Gagliardi

Josephine R Carlin

Harri G Ramjit

Edamanal S Venkataramani

Sagrario Mochales

Laura R Kauffman

Anthony D Theoharides

Donghui Cui

Nancy E Kohl

Thomayant Prueksaritanont

Amy M Hale

Susan J Danis

Raju Subramanian

Shieh-Shung J Chen

Amy M Bernick

Ralph A Stearns

Christine C Chung

Xiaojun Fang

Doss, George A

Claude Dufresne

Thomas A Baillie

Joel B Yudkovitz

The present invention relates to novel compounds formed by metabolic conversion of compounds of structural formula (1), pharmaceutical compositions containing such compounds, and their use as &agr;v&bgr;3 integrin receptor antagonists. The compounds of the present invention are useful for inhibiting bone resorption, restenosis, angiogenesis, diabetic retinopathy, macular degeneration, inflammatory arthritis, cancer, and metastatic tumor growth. They are particularly useful for inhibiting bone resorption and for the treatment and prevention of osteoporosis.

&agr; v integrin receptor antagonists

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

Biotransformation products of a fermentation with culture MA7074 are potent HIV protease inhibitors. These products are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Streptomyces sp. MA 7074 (ATCC 55605) used for microbial synthesis of

There are disclosed novel compounds which are derived from 22,23-dihydro avermectin B1 aglycone. The compounds are both isomers of the 27-hydroxy adduct of the substrate avermectin compound that have been glycosylated at the 4' position to yield 4'-O-glucosyl 27-OH avermectin compounds. The compounds and the intermediates used to make them are highly potent antiparasitic, insecticidal and anthelmintic avermectin agents.

Bioconversion products of 27-hydroxy avermectin

Cholesterol lowering compound

New cholesterol lowering compounds are formed from the photochemical treatment of zaragozic acid A.

Chemical compounds

New cholesterol lowering compounds are formed from the photochemical treatment of the zaragozic acids.

Cholesterol lowering compounds

Microbial transformation of a macrolide immunosuppressant by the microorganism Streptomyces sp., (Merck Culture Collection MA 6960) ATCC No. 55387 yields a compound of the structural formula (I): ##STR1## This compound is an immunosuppressant useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases, the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.

Microbial transformation product having immunosuppressive activity

Described is a new process for producing the immunosuppressant, L-682,993, a C-31 demethylated derivative of L-679,934 (FK-506), produced under fermentation conditions utilizing the new mutant microorganism Streptomyces sp. (Merck Culture Collection MA 7017) ATCC No. 55334, being a blocked second generation mutant of Streptomyces sp. (MA 6858) ATCC No. 55098. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Process for producing immunosuppressant agent

Zaragozic acids isolated from a culture of MF5465 have been subjected to photoreaction, then derivatized at the 4-keto position. The resulting derivatives are active as squalene synthetase inhibitors and are useful in the treatment of hypercholesterolemia.

Cholesterol lowering compounds and compositions are formed from the photochemical treatment of the Zaragozic Acids followed by esterification. These compounds and compositions are active squalene synthetase inhibitors useful in the treatment of hypercholesterolemia.

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors and thus useful as cholesterol lowering agents, antifungal agents and cancer treatment agents.

Cholesterol lowering compounds produced by directed biosynthesis

Described is a process for producing an immunosuppressant, 'demethimmunomycin' (L-683,7411) a C-31 demethylated analog of L-683,590 under fermentation conditions utilizing the microorganism, Actinoplanacete sp, (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Immunosuppressant agent

Described is a process for producing a new immunosuppressant, a C-31 desmethyl, C-19/C-22 cyclic hemiketal biotransformation analog (Compound I) of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces, lavendulae ATCC No. 55209. Also disclosed is the C-31 methylated derivative (Compound II) of Compound I produced by enzymatic methylation using 31-O-desmethylimmunomycin O-methyl transferase, (DIMT), a methyl transferase enzyme. The macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

C-31 desmethyl FR-900520 cyclic hemiketal immunosuppressant agent

Described is a new process for producing the immunosuppressant, L-683,742, a C-31 demethylated, derivative of L-683,590 (FK-520), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Process for producing immunosuppressant agent L-683942 by fermentation

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Watchung, NJ, United States of America

Byron H Arison