Author/Authors :
Martin W Rowbottom، نويسنده , , Fabio C. Tucci، نويسنده , , Yun-Fei Zhu، نويسنده , , Zhiqiang Guo، نويسنده , , Timothy D Gross، نويسنده , , Greg J. Reinhart، نويسنده , , Qui Xie، نويسنده , , R. Scott Struthers، نويسنده , , John Saunders، نويسنده , , Chen Chen، نويسنده ,
Abstract :
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 0.7 nM (Ki) for the human GnRH receptor, which was 8-fold better than the 2,6-difluorobenzyl analog.
