在第2位和第6位具有D-芳香族残基且第3位有变异的促黄体生成激素释放激素抑制类似物。

Inhibitory analogues of the luteinizing hormone-releasing hormone having D-aromatic residues in positions 2 and 6 and variation in position 3.

作者信息

Humphries J, Wan Y P, Folkers K, Bowers C Y

出版信息

J Med Chem. 1978 Jan;21(1):120-3. doi: 10.1021/jm00199a024.

Abstract

A single sc injection of 750 microgram/rat of [D-Phe2,Pro3,D-Phe6]-LH-RH on proestrus completely inhibited ovulation in 4-day cycling rats. Ovulation was inhibited partially at 375 microgram/rat. At the 720 microgram/rat dosage, analogues of LH-RH with D-Phe in positions 2 and 6, and with Sar, Arg, or Hyp in position 3, resulted in partial inhibitors and an inactive analogue with Thr substitution. In the same assay, analogues with D-Phe in position 2 and D-Trp in position 6 were partial inhibitors when D-Phe, Met, or Val were in position 3 and inactive with Ile substitution.

摘要

在动情前期对4日周期的大鼠单次皮下注射750微克/只的[D-苯丙氨酸2，脯氨酸3，D-苯丙氨酸6]-促黄体激素释放激素（LH-RH），可完全抑制排卵。在375微克/只时排卵受到部分抑制。在720微克/只的剂量下，2位和6位为D-苯丙氨酸且3位为Sar、精氨酸或Hyp的LH-RH类似物产生部分抑制剂，以及1种3位为苏氨酸替代的无活性类似物。在同一试验中，2位为D-苯丙氨酸且6位为D-色氨酸的类似物，当3位为D-苯丙氨酸、甲硫氨酸或缬氨酸时为部分抑制剂，而3位为异亮氨酸替代时无活性。