Title of article :
A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists
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 , , Xiaochuan Wang، نويسنده , , John Saunders، نويسنده , , Chen Chen، نويسنده ,
Abstract :
A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12, Ki=9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues.
