Author/Authors :
Fu-Sen Kang، نويسنده , , George Allan، نويسنده , , Jihua Guan، نويسنده , , Nareshkumar Jain، نويسنده , , Olivia Linton، نويسنده , , Pamela Tannenbaum، نويسنده , , Jun Xu، نويسنده , , Peifang Zhu، نويسنده , , Joseph Gunnet، نويسنده , , Xin Chen، نويسنده , , Keith Demarest، نويسنده , , Scott Lundeen، نويسنده , , Zhihua Sui، نويسنده ,
Abstract :
A novel series of oxa-steroids 6 derived from (8S, 13S, 14R)-7-oxa-estra-4,9-diene-3,17-dione 1 have been synthesized and identified as potent and selective progesterone receptor antagonists. These novel oxa-steroids showed similar potency to mifepristone. Preliminary SAR study resulted in the most potent 17-phenylethynyl oxa-steroid 6i wih an IC50 of 1.4 nM. In contrast to the equipotent mifepristone toward the progesterone receptor (PR) and glucocorticoid receptor (GR), compound 6i had over 200-fold selectivity for PR over GR.
Keywords :
Oxa-steroid , progesterone receptor , Antagonist , modulator , Glucocorticoid receptor , Selective PRM , Mifepristone , modeling
