Synthesis and structure-activity relationships of (R)-1-alkyl-3-[2-(2-amino)phenethyl]-5-(2-fluorophenyl)-6-methyluracils as human GnRH receptor antagonists.
Synthesis and structure-activity relationships of (R)-1-alkyl-3-[2-(2-amino)phenethyl]-5-(2-fluorophenyl)-6-methyluracils as human GnRH receptor antagonists.
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作为人 GnRH 受体拮抗剂的 (R)-1-烷基-3-[2-(2-氨基)苯乙基]-5-(2-氟苯基)-6-甲基尿嘧啶的合成和构效关系。
DOI：
10.1016/j.bmcl.2004.02.004
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Chen,Chen
中科院分区：
文献类型：
--
作者：
Rowbottom,MartinW;Tucci,FabioC;Zhu,Yun-Fei;Guo,Zhiqiang;Gross,TimothyD;Reinhart,GregJ;Xie,Qui;Struthers,RScott;Saunders,John;Chen,Chen
The synthesis of a series of (R)-1-alkyl-3-[2-(2-amino)phenethyl]-5-(2-fluorophenyl)-6-methyluracils is discussed. SAR around N-1 of the uracil was explored, which led to the discovery that an electron-deficient 2,6-disubstituted benzyl group is required for optimal receptor binding. The best compound from the series had binding affinity of 0.7nM (Ki) for the human GnRH receptor, which was 8-fold better than the 2,6-difluorobenzyl analog.
