Merck + Co., Inc.

Other

Robert T Goegelman

Sebastian Hernandez

Edward O Stapley

Frederick M Kahan

Jean S Kahan

Raymond F White

Patrick J Cassidy

Arthur A Patchett

Edward S Inamine

Jerrold M Liesch

David Taub

Louis Kaplan

Vincent P Gullo

Byron H Arison

Otto D Hensens

Laszlo R Treiber

John G Ondeyka

Kevin M Byrne

Yu L Kong

Gregory L Helms

Ruth S Sykes

E Tracy Turner Jones

Elvira Munguira

Maria T Diez Matas

Douglas L Cole

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

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

New immunosuppressive cyclosporin analogs are disclosed consisting of [dehydro-Ala].sup.8 cyclosporins and derived therefrom cyclosporins having a sulfur containing amino acid at position-8.

Synthesis of novel immunosuppressive cyclosporin analogs with modified

Immunosuppressive cyclosporin analogs with modified amino acids at

Disclosed is a novel lipophilic macrolide of Formula I: ##STR1## The compound of assigned Formula I is an analog of rapamycin which has activity as an antifungal agent and as an immunosuppressant.

Lipophilic macrolide useful as an immunosuppressant

Paraherquamide is a fungal metabolite isolated from the known fungus Penicillium paraherquei, and from a newly isolated strain of the fungus Penicillium charlesii. Additional compounds are disclosed which are related to paraherquamide and have been isolated from Penicillium charlesii. The compounds are potent antiparasitic agents. Compositions including such compounds as the active ingredient thereof for antiparasitic uses against endo and ecto parasites are also disclosed, as well as process for the preparation of such compounds from the newly isolated fungus.

Derivatives of paraherquamide isolated from a fermentation broth active

There is disclosed a series of macrolides isolated from the fermentation broth of a microorganism identified as MA-5920. This novel microorganism is formed by the protoplast fusion of strains of Streptomyces avermitilis and Streptomyces hygroscopicus. The structure of the novel compounds isolated from the microorganism is 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 microorganisms

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

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.

Novel averonectin fermentation product of a microorganism with

There are disclosed novel compounds which are derived from 22,23-dihydro avermectin Bla aglycone, 13-deoxy-22,23 dihydro overmectin Bla aglycone and 13-deoxy-22,23-dihydro overmectin Blb aglycone. The six compounds are hydroxy adducts of the substrate avermectin compound at the 12a, 24, 24a, 26, 26a and 27 positions. The hydroxy adducts are prepared by incubating the substrate with the microorganism Cunninghamella blakesleeana and isolating the hydroxy adducts from the fermentation broth. The compounds are highly potent antiparasitic, insecticidal and anthelmintic agents.

Avermectin bioconversion products

Non-ionic, lipophilic substances are isolated from aqueous or aqueous-organic solution by treatment with a macroreticular polymeric absorbent followed by elution with additional or a different organic solvent.

Isolation of non-ionic lipophilic materials on macroreticular polymeric

There are disclosed certain new compounds related to C-076 compounds which have been produced by a mutant of the culture that produced the original C-076 compounds and isolated from the fermentation broth thereof. The compounds retain the C-076 16-membered cyclic backbone, however, the groups attached thereto are considerably modified from the original C-076 compounds. The new compounds have been found to retain the biological activity of the parent C-076 compounds. The compounds are thus potent antiparasitic agents and compositions and methods for such uses are also disclosed.

Novel C-076 compounds

The antibiotic thienamycin is active against both gram-positive and gram-negative bacteria. The antibiotic is produced by growing a newly-found and hitherto undescribed species of Streptomyces on suitable fermentation media.

Culture of Streptomyces cattleya

There are disclosed certain new derivatives of C-076 compounds which have been isolated from the fermentation broth that produced the original C-076 compounds. The compounds retain the C-076 16-membered cyclic backbone, however, the groups attached thereto are considerably modified from the original C-076 compounds. The new compounds have been found to retain the biological activity of the parent C-076 compounds. The compounds are thus potent antiparasitic agents and compositions and methods for such uses are also disclosed.

Novel derivatives of C-076 compounds

The antibiotics MSD 890A.sub.1 and MSD 890A.sub.3 and pharmaceutically acceptable salts thereof (hereinafter referred to as antibiotics 890A.sub.1 and 890A.sub.3) are active against both gram-positive and gram-negative bacteria. The antibiotics are produced by growing species of Streptomyces on suitable fermentation media.

Growing community of inventors

Linden, NJ, United States of America

Robert T Goegelman