Synthesis and structure–activity relationships of uracil derived human GnRH receptor antagonists: (R)-3-[2-(2-amino)phenethyl]-1-(2,6-difluorobenzyl)-6-methyluracils containing a substituted thiophene or thiazole at C-5
2004; Elsevier BV; Volume: 14; Issue: 19 Linguagem: Inglês
10.1016/j.bmcl.2004.07.022
ISSN1464-3405
AutoresMartin W. Rowbottom, Fábio C. Tucci, Patrick J. Connors, Timothy D. Gross, Yunfei Zhu, Zhiqiang Guo, M. N. Moorjani, Oscar L. Acevedo, Lee Carter, Susan K. Sullivan, Qiu Xie, Andrew J. Fisher, R. Scott Struthers, John Saunders, Chen Chen,
Tópico(s)Fluorine in Organic Chemistry
ResumoThe synthesis of a series of (R)-3-[2-(2-amino)phenethyl]-1-(2,6-difluorobenzyl)-6-methyluracils containing a substituted thiophene or thiazole at C-5 is described. SAR around C-5 of the uracil led to the discovery that a 2-thienyl or (2-phenyl)thiazol-4-yl group is required for optimal receptor binding. The best compound from the series had a binding affinity of 2 nM (Ki) for the human GnRH receptor. A novel and convenient preparation of N-1-(2,6-difluorobenzyl)-6-methyluracil is also described.
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