Synthesis, in vivo and in vitro biological activity of novel azaline B analogs

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 11; pp. 2894 - 2897
• Main Authors: Samant, Manoj P., Gulyas, Jozsef, Hong, Doley J., Croston, Glenn, Rivier, Catherine, Rivier, Jean
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02-06-2005; Elsevier
• Subjects: Animals; Azaline B; Biological and medical sciences; Cell Line; Chromatography, High Pressure Liquid; Degarelix; GnRH antagonists; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropin-Releasing Hormone - chemical synthesis; Gonadotropin-Releasing Hormone - chemistry; Gonadotropin-Releasing Hormone - pharmacology; Hormones. Endocrine system; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Structure activity relationships; GnRH antagonists; Structure activity relationships; Azaline B; Degarelix; Oligopeptides; Peptides; Rat; Rodentia; Gonadotropin RH; Male; In vitro; In vivo; Vertebrata; Mammalia; Structure activity relation; Animal; Luteinizing hormone; Affinity; Antagonist; Chemical synthesis; Duration of action; Hormonal receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.03.085

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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.