Merck + Co., Inc.

Edward S Inamine

Shieh-Shung T Chen

Byron H Arison

Raymond F White

Linda S Wicker

David R Houck

Robert T Goegelman

George D Hartman

Robert L Smith

Wasyl Halczenko

Gerald E Stokker

Otto D Hensens

Ta J Lee

Brian R Petuch

George M Garrity

Michael A Goetz

Sagrario Mochales

Joanne M Williamson

Jerome Birnbaum

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 new immunosuppressant, L-683,519, a monodemethylated rearranged derivative of L-679,934, (FK-506) produced under fermentation conditions utilizing the microorganism, unidentified Actinomycete (Merck Culture Collection MA 6474) ATCC No. 53828. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Microbial transformation product of L-679,934

Described is a new immunosuppressant, L-683,756, a bisdemethylated, ring rearranged derivative of L-683,590, produced 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.

Microbial immunosoppressant agent

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

Described is a new microorganism, Actinoplanacete sp., (Merck Culture Collection MA 6559) ATCC No. 53771. The microorganism acts as a demethylating agent and can produce the new immunosuppressants, 'demethomycin' (L-682,993) a C-31 demethylated analog of L-679,934, and 'demethimmunomycin' (L-683,742) a C-31 demethylated analog of L-683,590, under novel fermentation conditions. These macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Immunosuppressant-producing culture

Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are useful as antihypercholesterolemic agents and are represented by the following general structural formula (II): ##STR1##

HMG-CoA reductase inhibitors

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.

Novel avermectins are produced from known microorganisms

A microbiological process is described for the preparation of 6-desmethyl-6-.beta.-hydroxymethyl and 6-desmethyl-6-.beta.-carboxylovastatin derivatives and 8-acyl analogs thereof.

HMG-CoA reductase inhibitors produced by Nocardia sp. (MA 6455)

Described is a process for producing a new immunosuppressant, 'demethomycin' (L-682,993) a C-31 demethylated analog of L-679,934 under novel fermentation conditions utilizing the microorganism, Actinoplanacete sp., (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide immunosuppressant is useful in prevent human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Immunosuppressant compound

Described is a new immunosuppressant, L-685,487, a monodemethylated rearranged derivative of L-683,590, produced under fermentation conditions utilizing the microorganism, unidentified Actinomycete (Merck Cultrue Collection MA 6474) ATCC No. 53828. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Microbial transformation product of L-683,590

Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are useful as anti-hypercholesterolemic agents and are represented by the following general structural formulae (I) and (II): ##STR1##

Novel HMG-CoA reductase inhibitors

There are disclosed macrolides isolated from the fermentation broth, with avermectin Bla, avermectin Blb or 22,23-dihydro avermectin Bla as a substrate, of a known microorganism identified as MA-6181. The structure of the novel compounds isolated from the microorganism are presented based upon analytical studies. The compounds are highly potent antiparasitic, insecticidal, and anthelmintic agents. Compositions for such uses are also disclosed.

Anthelmintic fermentation products of a microorganism

Products of Aspergillus alliaceus fermentation having cholecystokinin (CCK) antagonist activity, their preparation and use are disclosed.

Cholecystokinin antagonist compounds

There is disclosed a macrolide isolated from the fermentation broth, with 22,23-dihydro avermectin Bla aglycone as a substrate, of a known microorganism identified as MA-5853. The structure of the novel compound isolated from the microorganism is presented based upon analytical studies. The compound is a highly potent antiparasitic, insecticidal, and anthelmintic agent. Compositions for such uses are also disclosed.

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Rahway, NJ, United States of America

Edward S Inamine