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.
Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA. john.randolph@abbott.com
John T
JT
Randolph
Daryl R
DR
Sauer
Fortuna
F
Haviv
Angela M
AM
Nilius
Jonathan
J
Greer
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004917:Erythromycin / Q000737:chemistry* / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011485:Protein Binding / Q000502:physiology; D013210:Staphylococcus / Q000187:drug effects / Q000254:growth & development; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007987:Gonadotropin-Releasing Hormone; D004917:Erythromycin