Nonsteroidal Progesterone Receptor Modulators: Structure Activity Relationships

Richard C. Winneker; Andrew Fensome; Jay E. Wrobel; Zhiming Zhang; Puwen Zhang

doi:10.1055/s-2005-864033

Seminars in Reproductive Medicine, Inhaltsverzeichnis

Semin Reprod Med 2005; 23(1): 46-57
DOI: 10.1055/s-2005-864033

Nonsteroidal Progesterone Receptor Modulators: Structure Activity Relationships

Richard C. Winneker¹ , Andrew Fensome² , Jay E. Wrobel² , Zhiming Zhang¹ , Puwen Zhang²

¹Endocrinology and Reproductive Disorders Division, Women's Health Research Institute
²Chemical & Screening Sciences, Wyeth Research, Collegeville, Pennsylvania

Abstract

ABSTRACT

Progesterone, acting primarily via the progesterone receptor (PR), plays an essential role in the regulation of female reproduction. Steroidal progestins (i.e., PR agonists) are commonly used in women's health, such as in contraception and hormone therapy and for the treatment of gynecological disorders. Recent studies in women and in nonhuman primates also indicate that PR antagonists may have potential applications in contraception and for the treatment of reproductive disorders such as fibroids and endometriosis. Currently, all clinically available PR agonists and antagonists are steroidal compounds. They often cause various side effects due to their functional interactions with other steroid receptors or because of effects associated with their steroidal metabolites. In an effort to identify more receptor-selective and structurally diverse compounds that may render clinical advantages over steroidal PR ligands, numerous receptor-selective novel nonsteroidal PR agonists and antagonists have been discovered. This review focuses on the structure activity relationships and the biological profile of the nonsteroidal PR modulators discovered in the last decade.

KEYWORDS

Progesterone receptor (PR) - PR agonists - PR antagonists - contraception - endometriosis - hormone therapy - uterine fibroids

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Richard C WinnekerPh.D.

Women's Health Research Institute, Wyeth Research

500 Arcola Road, Collegeville, PA 19426

eMail: winnekr@wyeth.com