Parallel synthesis of substituted pyridones for use as Gonadotropin Releasing Hormone (GnRH) antagonists

MEDI 82

Daniel Green, greend@wyeth.com1, Jeffrey C. Pelletier2, Murty V. Chengalvala3, Joshua E. Cottom3, and Linda Shanno3. (1) Department of Chemical & Screening Sciences, Wyeth Research, 500 Arcola Rd., Collegeville, PA 19426, (2) Department of Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, (3) Department of Women's Health and Musculoskeletal Biology, Wyeth Research, 500 Arcola Rd, Collegeville, PA 19426
Gonadotropin Releasing Hormone antagonists are useful in the treatment of sex-hormone dependant disorders such as endometriosis, breast and prostate cancer, and precocious puberty in children. Currently approved therapy is limited to peptide antagonists and superagonists, which are delivered via parenteral routes. Our goal was to develop a small molecule orally available antagonist for the treatment of these diseases. Working off an advanced lead compound, parallel synthesis was employed to rapidly explore the potential biological activity of substituted pyridones against GnRH. In vitro potency, functional activity, metabolism, and pharmaceutical properties will be discussed.

 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007