Zhu Yun-Fei, Guo Zhiqiang, Gross Timothy D, Gao Yinghong, Connors Patrick J, Struthers R Scott, Xie Qiu, Tucci Fabio C, Reinhart Greg J, Wu Dongpei, Saunders John, Chen Chen
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, California 92121, USA.
J Med Chem. 2003 Apr 24;46(9):1769-72. doi: 10.1021/jm0205402.
SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.
作为非肽类人促性腺激素释放激素（GnRH）受体拮抗剂，对7-苯基吡咯并[1,2-a]嘧啶-4-酮1和2以及2-苯基咪唑并[1,2-a]嘧啶3和4进行的构效关系（SAR）研究使我们相信，一旦在6位引入芳基，4位2-位的芳环对于结合就不再至关重要。我们在此报告在咪唑并[1,2-a]嘧啶酮核心上使用2-烷基来生成强效GnRH受体拮抗剂。这一发现使我们能够获得更小但同样有效的GnRH受体拮抗剂。
