Synthesis of Some Di-and Tri-Substituted Analogs of Luteinizing Hormone Releasing Hormone (LH-RH)

Abstract

Eight new di- and tri-substituted luteinizing hormone releasing hormone (LH-RH) analogs, i.e., des-Gly¹⁰-[Thr⁴]-LH-RH-ethylamide, des-Gly¹⁰-[Phe⁵]-LH-RH-ethylamide, des-Gly¹⁰-[Phe⁵, Ile⁷]-LH-RH-ethylamide, des-Gly¹⁰-[Nle⁷]-LH-RH-ethylamide, des-Gly¹⁰-[Met⁷]-LH-RH-ethylamide, des-Gly¹⁰-[Orn⁸]-LH-RH-ethylamide, des-Gly¹⁰-[Lys⁸]-LH-RH-ethylamide and des-Gly¹⁰-[Gly⁹]-LH-RH-ethylamide, were synthesized by the solution method, and tested in vitro for the ability to induce secretion of luteinizing hormone. On the basis of structure-activity relations of these analogs, it is concluded that the effect of several structural changes in the LH-RH-molecule on its hormonal activity is"additive".