Novel 3-Aryl Indoles as Progesterone Receptor Antagonists for Uterine Fibroids
作者
RICHARDSON TIMOTHY I; CLARKE CHRISTIAN A; YU KUOLONG; YEE YING K; BLEISCH THOMAS J; LOPEZ JOSE E; JONES SCOTT A; HUGHES NORMAN E; MUEHL BRIAN S; LUGAR CHARLES W; MOORE TERRY L; SHETLER PAMELA K; ZINK RICHARD W; OSBORNE JOHN J; MONTROSERAFIZADEH CHAHRZAD; PATEL NITA; GEISER ANDREW G; GALVIN RACHELLE J SELLS; DODGE JEFFREY A
[摘要]：We report the synthesis and characterization of novel 3-aryl indoles as potent and efficacious progesterone receptor (PR) antagonists with potential for the treatment of uterine fibroids. These compounds demonstrated excellent selectivity over other steroid nuclear hormone receptors such as the mineralocorticoid receptor (MR). They were prepared from 2-bromo-6-nitro indole in four to six steps using a Suzuki Cross-coupling as the key step. Compound 8f was orally active in the complement 3 model of progesterone antagonism in the rat uterus and demonstrated partial antagonism in the McPhail model of progesterone activity.
