Synthesis and Structure–Activity relationships of 1-arylmethyl-3-(2-aminopropyl)-5-aryl-6-methyluracils as potent GnRH receptor antagonists

…, Y Gao, RS Struthers, J Saunders, TD Gross…

Index: Guo, Zhiqiang; Zhu, Yun-Fei; Tucci, Fabio C.; Gao, Yinghong; Struthers, R. Scott; Saunders, John; Gross, Timothy D.; Xie, Qiu; Reinhart, Greg J.; Chen, Chen Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 19 p. 3311 - 3315 Title/Abstract Full Text View citing articles Show Details Rowbottom, Martin W.; Tucci, Fabio C.; Connors Jr., Patrick J.; Gross, Timothy D.; Zhu, Yun-Fei; Guo, Zhiqiang; Moorjani, Manisha; Acevedo, Oscar; Carter, Lee; Sullivan, Susan K.; Xie, Qiu; Fisher, Andrew; Struthers, R. Scott; Saunders, John; Chen, Chen Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 19 p. 4967 - 4973

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Citation Number: 21

Abstract

The novel synthesis and SAR studies of 6-methyluracils as human GnRH receptor antagonists are discussed. Introduction of a small methyl substituent at the β-position from N3 of the uracil improved the GnRH binding potency by 5-to 10-fold. The best compound from the series had binding affinity of 5 nM (Ki) to the human GnRH receptor.