Synthesis, in vivo and in vitro biological activity of novel azaline B analogs.
Several azaline B analogs (2-10) were synthesized and evaluated for their ability to antagonize GnRH in vitro and for duration of action in inhibiting luteinizing hormone secretion in a castrated male rat assay in vivo. Analogs, 8 (IC(50) = 1.85 nM), and 9 (IC(50) = 1.78 nM), are equipotent with azaline B (1, IC(50) = 1.36 nM) in vitro. Whereas 9 is short acting, 8 is as long acting as azaline B. Other analogs have IC(50) greater than 2.0 nM and are all short acting.
Samant
Manoj P
MP
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA.
Gulyas
Jozsef
J
Hong
Doley J
DJ
Croston
Glenn
G
Rivier
Catherine
C
Rivier
Jean
J
D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D051381:Rats
C070464:azaline; D007987:Gonadotropin-Releasing Hormone