Merck + Co., Inc.

Raymond F White

Shieh-Shung T Chen

Byron H Arison

Edward S Inamine

Brian R Petuch

Robert T Goegelman

John G MacConnell

Robert E Schwartz

George M Garrity

Leeyuan Huang

Georgette Dezeny

Lydia T So

Arthur A Patchett

Otto D Hensens

Jerrold M Liesch

Thomas R Beattie

Dennis M Schmatz

Henry Joshua

Louis Kaplan

Jon D Polishook

Francis J Dumont

Kevin M Byrne

Magda M Gagliardi

Amy M Hale

Kalinka Shumanov

Amy M Bernick

Bryon H Arison

Cholesterol lowering compound

A cyclosporin derivative with incorporated '8-(3-fluoro-D-alanine)' or '8-(2-deutero-3-fluoro-D-alanine)' has been isolated from the fermentation broth of incubating Tolypocladium inflatum MF5080 (NRRL 8044) with 3-fluoro-D-alanine or its 2-deuterated isomer respectively. The modified cyclosporins exhibit immunosuppressive properties.

Method for the production of a modified '8-amino acid' cyclosporin

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

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds 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.

Directed biosynthesis of biologically active compounds

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

This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents. The compounds also exhibit antifungal activity and are inhibitors of farnesyl-protein transferase.

Cholesteral lowering agents

Incubation of 13.beta.-hydroxy ivermectin aglycone with a species of Bacillus subtilis or the incubation of 13-deoxy ivermectin aglycone with a mixed culture of a species of Bacillus subtilis and of Streptomyces griseus results in the production of 13-.beta. ivermectin monoglucopyranoside as the major product and of 5-.beta. ivermectin monoglucopyranoside as the minor product.

Biotransformation process for the production of invermectin derivatives

The known compound, 13.beta.-13-deoxy-22,23-dihydro-avermectin -B1a/B1b Aglycone is prepared microbiologically from cultures of the novel microorganisms (MA-6762, ATCC 55069, MA-6763 ATCC 55070) or the known microorganism Streptomyces lavendulae MA-6555 (ATCC 14159 or ATCC 55330). The compound is prepared by the biotransformation of 13-deoxy-22,23-dihydro avermectin B1a/B1b aglycone which oxidizes the 13-position and epimerizes the 13-position hydroxy group.

Microbial preparation of 13.beta.-13-deoxy-22,23-dihydro

Described is a process for producing a new immunosuppressant, a C-19/C-22 cyclic hemiketal (Compound I) biotransformation analog of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces sp. (Merck Culture Collection MA6963) ATCC No. 55230. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

Cyclcic FR-900520 microbial biotransformation agent

Fermentation of the microorganism Streptomyces sp. MA6966 (ATCC 55293) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields a new compound hydroxylated in the 2-butyl group which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Antihypertensive compound and method of use thereas

Fermentation of the microorganism Actinoplanes sp. MA6559 (ATCC 53771) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields a new compound, hydroxylated in the 2-butyl group, which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Actinoplanes transformation process anti-hypertensive compound and

An antibiotic agent produced by the cultivation of Zalerion arboricola which is a cyclic lipopeptide with very high activity against human pathogens and of very low mammalian toxicity is described. Its production and isolation are also described.

Antibiotic cyclopeptide fermentation product

Antibiotic agent

Fermentation of the microorganism Streptomyces sp. (MA6750) ATCC No. 55042 in the presence of the Angiotensin II (A II) receptor antagonist of the following structure: ##STR1## yields an analog having a shikimate sugar-like moiety attached to the tetrazole, the said analog which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II angatonists.

Microbial transformation process for producing an antihypertensive

Incubation of 13-deoxy ivermectin aglycone with a species of B. subtilis and of S. griseus results in the production of 13-.beta. ivermectin monoglucopyranoside as the major product and of 5-.beta. ivermectin monoglucopyranoside as the minor product.

Growing community of inventors

Englishtown, NJ, United States of America

Raymond F White