Humphries J, Wan Y P, Folkers K, Bowers C
J Med Chem. 1977 Dec;20(12):1674-7. doi: 10.1021/jm00222a028.
A series of ten analogues, of structure des-Gly10-[amino acid2, amino acid3,D-Ala6]-LH-RH ethylamide, was synthesized by solid-phase methods. L-Aromatic and alkylamino acids were substituted into position 2 and alkylamino acids into position 3. Highest in vitro inhibition of LH-RH action was obtained with analogues having aromatic residues in position 2. Des-Gly10-[Trp2,Leu3,D-Ala6]-LH-RH ethylamide inhibited the action of 0.6 ng/mL of LH-RH, in an isolated pituitary assay, at a dosage as low as 1 microgram/mL, and the corresponding Phe2 analogue inhibited the effect of 0.3 ng of LH-RH at 0.1 microgram/mL. The Trp2 analogue inhibited ovulation in rats at the dosage of 1.5 mg per rat.
通过固相法合成了一系列十个结构为去甘氨酸10-[氨基酸2，氨基酸3，D-丙氨酸6]-促黄体生成素释放激素乙酰胺的类似物。将L-芳香族和烷基氨基酸取代到第2位，将烷基氨基酸取代到第3位。在第2位具有芳香族残基的类似物在体外对促黄体生成素释放激素作用的抑制作用最强。在离体垂体试验中，去甘氨酸10-[色氨酸2，亮氨酸3，D-丙氨酸6]-促黄体生成素释放激素乙酰胺在低至1微克/毫升的剂量下就能抑制0.6纳克/毫升促黄体生成素释放激素的作用，相应的苯丙氨酸2类似物在0.1微克/毫升时能抑制0.3纳克促黄体生成素释放激素的作用。色氨酸2类似物以每只大鼠1.5毫克的剂量抑制大鼠排卵。
