Title of article :
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
Author/Authors :
Martin W. Rowbottom، نويسنده , , Fabio C. Tucci، نويسنده , , Patrick J. Connors Jr.، نويسنده , , Timothy D. Gross، نويسنده , , Yun-Fei Zhu، نويسنده , , Zhiqiang Guo، نويسنده , , Manisha Moorjani، نويسنده , , Oscar Acevedo، نويسنده , , Lee Carter، نويسنده , , Susan K. Sullivan، نويسنده , , Qiu Xie، نويسنده , , Andrew Fisher، نويسنده , , R. Scott Struthers، نويسنده , , John Saunders، نويسنده , , Chen Chen، نويسنده ,
Abstract :
The 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.
