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 (IC50 = 1.85 nM), and 9 (IC50 = 1.78 nM), are equipotent with azaline B (1, IC50 = 1.36 nM) in vitro. Whereas 9 is short acting, 8 is as long acting as azaline B. Other analogs have IC50 greater than 2.0 nM and are all short acting.