Merck + Co., Inc.

Yu L Kong

Deborah L Zink

Sheo B Singh

Robert A Giacobbe

Leeyuan Huang

Michael A Goetz

E Tracy Jones

E Tracy Turner Jones

Siobhan Stevens-Miles

Otto D Hensens

Jerrold M Liesch

Robert T Goegelman

Fernando Pelaez

Russell B Lingham

Keith C Silverman

Sagrario M Del Val

Yiu-kuen T Lam

Maria T Diez

Guy H Harris

Isabel Martin

Jon D Polishook

Claude Dufresne

Carol F Wichmann

Gregory L Helms

Maria S Meinz

Wendy H Clapp

Leeyan Huang

Ruth S Sykes

Lucia Herranz

Gerard F Bills

Robert A Giocobbe

Elvira Munguira

Maria T Diez Matas

Josep Guarro

This invention relates to compounds of structural formula (I) isolated from an aerobic fermentation of Trichoderma viride MF5628, ATCC 74084: ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents. These compounds are also potent antifungal agents. Additionally, they inhibit farnesyl protein transferase and farnesylation of the oncogene protein Ras and are thus useful in treating cancer. This invention also relates to a process for obtaining compounds of structural formula (I).

Biologically active compounds isolated from aerobic fermentation of

Fermentation processes for the production of a compound of the Structural Formula I ##STR1## The compound of Structural Formula I has been shown to have endothelin antagonist activity and is therefore useful in treating cardiovascular disorders, such as hypertension, congestive heart failure, postischemic renal failure vasospasm, cerebral and cardia ischemia, myocardial infarction inflammatory diseases, Raynaud's disease, endotoxin shock and asthma.

Process for the production of a novel endothelin antagonist

There is disclosed a series of macrolides isolated from the fermentation broth of microorganisms identified as MA-6825, MA-6864 and MA-6865. The structure of the novel compounds isolated from the microorganisms is presented based upon analytical studies. The compounds are highly potent antiparasitic, insecticidal, and anthelmintic agents and are related to the class of macrolides known as milbemycins. Compositions for such uses are also disclosed.

Anthelmintic milbemycin analogs of novel microorganisms

This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents and antifungal agents. These compounds are also inhibitors of farnesyl protein transferase and farnesylation of the oncogene protein Ras and thus useful in treating cancer. This invention also relates to a process for obtaining compounds of structural formula (I).

Cholesterol-lowering agents

Substituted hexahydrobenzopyran derivatives of the Formulae A, B, or C are useful as angiotensin II antagonists: ##STR1##

Substituted hexahydrobenzopyran derivatives as angiotensin II antagonists

This invention relates to a fungal microorganism MF5757 (ATCC 74167) isolated from bark discs of Quercus prinus L. (Chestnut Oak) and useful in a fermentation process to form a compound of formula (I): ##STR1## which is a squalene synthetase inhibitor and thus useful as a cholesterol lowering agent.

Fungal microorganism ATCC 74167 capable of producing cholesterol

Fermentation of a nutrient medium by a Hypomycetes fungus of the genus Memnoniella or Stachybotrys yields a product with a major component of structural formula I: ##STR1## which is an inositol monophosphate phosphatase inhibitor and thereby useful in the treatment of manic depression.

Drug for treating manic depression

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Edison, NJ, United States of America

Yu L Kong