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Novel 3-Aryl Indoles as Progesterone Receptor Antagonists for Uterine Fibroids

2010; American Chemical Society; Volume: 2; Issue: 2 Linguagem: Inglês

10.1021/ml100220b

1948-5875

Timothy I. Richardson, Christian A. Clarke, Kuo‐Long Yu, Ying K. Yee, Thomas J. Bleisch, José Enrique López, Scott A. Jones, Norman E. Hughes, Brian S. Muehl, Charles W. Lugar, Terry L. Moore, Pamela K. Shetler, Richard W. Zink, John Osborne, Chahrzad Montrose‐Rafizadeh, Nita Patel, Andrew G. Geiser, Rachelle J. Sells Galvin, Jeffrey A. Dodge,

Estrogen and related hormone effects

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.