Author/Authors :
Chen Chen، نويسنده , , Yongsheng Chen، نويسنده , , Joseph Pontillo، نويسنده , , Zhiqiang Guo، نويسنده , , Charles Q. Huang، نويسنده , , Dongpei Wu، نويسنده , , Ajay Madan، نويسنده , , Takung Chen، نويسنده , , Jenny Wen، نويسنده , , Qiu Xie، نويسنده , , Fabio C. Tucci، نويسنده , , Martin Rowbottom، نويسنده , , Yun-Fei Zhu، نويسنده , , Warren Wade، نويسنده , , John Saunders، نويسنده , , Haig Bozigian، نويسنده , , R. Scott Struthers، نويسنده ,
Abstract :
Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a Ki of 2.2 nM at GnRH-R and an IC50 of 36 μM at CYP3A4.
Keywords :
CYP3A4 , inhibition , structure–activity relationship , Zwitterion , Gonadotropin-Releasing Hormone , receptor , Antagonist
