Synthesis and biological activity of some analogs of the gonadotropin releasing hormone

Article abstract of DOI:10.1021/jm00249a012

Twenty one analogs of gonadotropin releasing hormone 2 (GnRH), were synthesized by the solid phase method. The derivatives were 3 (GnRH methyl ester), GnRH N methyl amide, GnRH free acid, 2 (Gn RH N terminal hexapeptide), and also [Ac Ala¹], [Ac gly¹], [D 1], [Pro¹], [Arg²], [Tyr(Me)³], [Ser⁵], [des Gly⁶], [Sar⁶], [des Pro⁹], [des Gly¹⁰, Pro NH₂⁹], [des Gly¹⁰, Pro NHC₂H₅⁹], [Tyr¹¹], [Tyr(Me)³⁵], [des His², des Pro⁹], [des His², Sar⁶], and [Sar⁶ des Tyr⁵] GnRH. All analogs were purified at both the protected and the deblocked stage. The final products were characterized by chemical and physical methods and assayed in vitro for both LH and FSH release using rat pituitaries. Those derivatives which showed less than 0.2% of the activity of GnRH itself were further tested for inhibition of gonadotropin release.