Folkers K, Bowers C Y, Kubiak T, Stepinski J
Biochem Biophys Res Commun. 1983 Mar 29;111(3):1089-95. doi: 10.1016/0006-291x(83)91411-0.
[N-Ac-D-2-Nal1,pCl-D-Phe2,D-3-Pal3,D-Arg6,D-Ala10]-LHRH caused 100% and 57% inhibition of ovulation in rats, s.c., at 500 and 250 ng, respectively, and 56%, per os at 500 micrograms. [N-Ac-3,4-diC1-D-Phe1,pC1-D-Phe2,D-3-Pal3,D-Arg6,D-Ala10]-LHRH inhibited ovulation, s.c., 82% at 500 ng, and 63%, per os at 500 micrograms. These analogs are the most effective reported inhibitors of ovulation. The new introduction of pyridyl-alanines can be superior substituents. For pairs of analogs, relationships are: D-3-Pal (beta-(3-pyridyl)-D-alpha-alanine) in position 3 is superior to D-Trp3, D-2-Pal3 and D-4-Pal3. D-Arg6 was superior to D-3-Pal6 and D-4-Pal6 was superior by 2-fold to D-Arg6. D-Ala10 was superior to Gly10 and D-Abu10.
[N-乙酰基-D-2-萘丙氨酸1、对氯-D-苯丙氨酸2、D-3-吡啶丙氨酸3、D-精氨酸6、D-丙氨酸10]-促黄体生成素释放激素分别以500纳克和250纳克的剂量皮下注射时，对大鼠排卵的抑制率分别为100%和57%，以500微克的剂量口服时抑制率为56%。[N-乙酰基-3,4-二氯-D-苯丙氨酸1、对氯-D-苯丙氨酸2、D-3-吡啶丙氨酸3、D-精氨酸6、D-丙氨酸10]-促黄体生成素释放激素皮下注射时，以500纳克的剂量对排卵的抑制率为82%，以500微克的剂量口服时抑制率为63%。这些类似物是已报道的最有效的排卵抑制剂。吡啶基丙氨酸的新引入可能是更好的取代基。对于成对的类似物，关系如下：3位的D-3-吡啶丙氨酸（β-(3-吡啶基)-D-α-丙氨酸）优于D-色氨酸3、D-2-吡啶丙氨酸3和D-4-吡啶丙氨酸3。D-精氨酸6优于D-3-吡啶丙氨酸6，D-4-吡啶丙氨酸6比D-精氨酸6优越2倍。D-丙氨酸10优于甘氨酸10和D-氨基丁酸10。
