Eli Lilly and Company

Debono, Manuel

Manuel Debono

R Michael Molloy

Jeffrey S Nissen

Frederick J Burkhardt

Herbert A Kirst

William Wilson Turner, Jr

Robert L Hamill

Raymond C Yao

David S Fukuda

Bernard J Abbott

Anne H Dantzig

Dennis R Berry

William W Turner

Kurt E Merkel

Patrick J Baker

Robert E Weeks

Khadiga Z Farid

Herald J Cole

Rosanne Bonjouklian

Ramakrishnan Nagarajan

Milton J Zmijewski

Gary G Marconi

Amelia A Schabel

Charles M Deber

James P Leeds

Julie A Wind

Douglas R Pfeiffer

Robert M Logan

Donner F Babcock

Provided are compounds of the formula (1): wherein R' is hydrogen, methyl or NHC(O)CH&#x2014;;

Cyclic peptide antifungal agents and process for preparation thereof

Two new groups of A-21978C cyclic peptides, anhydro- and isomer-A21978C peptide derivatives, have antibacterial activity and are useful as intermediates. The two groups are prepared via transpeptidation of the parent cyclic peptides. Pharmaceutical formulations containing the new peptides as active ingredients and methods of treating infections caused by susceptible Gram-positive bacteria with the formulations are also provided. The invention also provides an antibacterial composition containing the new drug substance LY 146032 in substantially pure form.

Anhydro-and isomer-a-21978c cyclic peptides

Provided are compounds of the formula (1):wherein R' is hydrogen, methyl or NHC(O)CH&#x2014;;

A82846-related glycopeptide compounds are prepared by treating an antibiotic selected from A82846 components A, B and C with trifluoroacetic acid to remove 1) the .alpha.-L-O-4-epi-vancosaminyl group attached to the disaccharide; 2) the (.alpha.-L-O-4-epi-vancosaminyl-.beta.-O-glucosyl) disaccharide group or 3) both the disaccharide group and the .alpha.-L-O-4-epi-vancosaminyl group attached to the peptide core from these antibiotics. The compounds have antibacterial activity, especially against Gram-positive microorganisms.

A-82846-type glycopeptide antibiotics

Provided are compounds of the formula (1): ##STR1## wherein R' is hydrogen, methyl or NH.sub.2 C(O)CH.sub.2 --;

Cyclic peptide antifungal agents

Anhydro- and isomer-A-21978C cyclic peptides

New glycopeptides prepared by biotransformation of a vancomycin-type antibiotic by an Acinomadura citrea culture (NRRL 18382), which are useful intermediates, and methods of preparing the biotransformed intermediates by adding a vancomycin-type glycopeptide to a growing culture of Actinomadura citrea NRRL 18382 and continuing fermentation under submerged aerobic conditions, are provided.

Biotransformation of glycopeptide antibiotics

Fermentation product A87689 is produced by a strain of Amycolatopsis mediterranei selected from NRRL 18815 and NRRL 18851, or an A87689-producing mutant thereof. A87689, its C.sub.1-6 -alkyl ether and C.sub.1-6 -alkanoyl ester derivatives and pharmaceutically acceptable salts thereof are phospholipase A.sub.2 inhibitors that are useful as antiinflammatory agents. Fermentation products known as BU-3889V, its components and pharmaceutically acceptable salts thereof, are phospholipase A.sub.2 inhibitors that are also useful as antiinflammatory agents.

A87689 compounds

A87689 compounds employed as a phospholipase A.sub.2 (PLA.sub.2)

Amycolatopsis mediterranei strains useful to prepare A87689 compounds

Three new groups of 9-N-substituted derivatives of erythromycylamine with superior oral activity against Gram-positive pathogens, new processes for preparing derivatives of erythromycylamine and aliphatic aldehydes by controlling the pH of the reaction and by catalytic hydrogenation, and pharmaceutical compositions and methods using the new compounds are provided.

Derivatives of erythromycylamine

C-20-Dihydro-deoxy-(cyclic amino)-derivatives of the macrolide antibiotics tylosin, desmycosin, macrocin, lactenocin, 2''-O-demethylmacrocin and 2'-O-demethyllactenocin, which inhibit pathogenic bacteria, especially gram-positive bacteria, Pasteurella species, and Mycoplasma species, and pharmaceutical compositions thereof, are provided.

C-20-dihydro-deoxy-(cyclic amino)-derivatives of macrolide antibiotics

Growing community of inventors

Indianapolis, IN, United States of America

Manuel Debono