Bioorganic & Medicinal Chemistry Letters 2003-10-06

Synthesis and structure-activity relationships of 1-arylmethyl-3-(2-aminopropyl)-5-aryl-6-methyluracils as potent GnRH receptor antagonists.

Zhiqiang Guo, Yun-Fei Zhu, Fabio C Tucci, Yinghong Gao, R Scott Struthers, John Saunders, Timothy D Gross, Qiu Xie, Greg J Reinhart, Chen Chen

Index: Bioorg. Med. Chem. Lett. 13(19) , 3311-5, (2003)

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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 beta-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 (K(i)) to the human GnRH receptor.