Author/Authors :
Fabio C. Tucci، نويسنده , , Yun-Fei Zhu، نويسنده , , Zhiqiang Guo، نويسنده , , Timothy D. Gross، نويسنده , , Patrick J. Connors Jr.، نويسنده , , R. Scott Struthers، نويسنده , , Greg J. Reinhart، نويسنده , , John Saunders، نويسنده , , Chen Chen، نويسنده ,
Abstract :
A new class of small molecule GnRH antagonists, the 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils, was designed and a novel stereoselective synthesis for these compounds was developed. The stereochemical integrities of key intermediates (S)-6 and (R)-6 were confirmed by a combination of X-ray crystallography and chiral HPLC determinations. SAR studies were performed, which allowed the identification of derivatives (R)-9f, (R)-9h and (R)-12 as potent hGnRH antagonists (Ki=20 nM).
