Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity

…, GR Kieczykowski, YT Yang, JB Yudkovitz, J Cui…

文献索引：Ashton, Wallace T.; Sisco, Rosemary M.; Kieczykowski, Gerard R.; Yang, Yi Tien; Yudkovitz, Joel B.; Cui, Jisong; Mount, George R.; Ren, Rena Ning; Wu, Tsuei-Ju; Shen, Xiaolan; Lyons, Kathryn A.; Mao, An-Hua; Carlin, Josephine R.; Karanam, Bindhu V.; Vincent, Stella H.; Cheng, Kang; Goulet, Mark T. Bioorganic and Medicinal Chemistry Letters, 2001 , vol. 11, # 19 p. 2597 - 2602

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被引用次数: 54

摘要

Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and ...