Elimination of antibacterial activities of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A

Antibacterial SAR for a series of macrolides derived from erythromycin A that are potent LHRH antagonists was developed in an attempt to eliminate the antibiotic activities of these compounds. Increasing the size of the alkyl substituents on the desosamine 3'-amine resulted in potent LHRH antagonists that were inactive against staphylococcal bacteria strains, and were significantly (> 10-fold) less active against streptococcal bacteria strains. Complete elimination of antibacterial activities could be achieved by replacement of one or both methyl groups on the 3'-amine with a large alkyl substituent. (C) 2003 Elsevier Ltd. All rights reserved.