Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potent and selective nonsteroidal progesterone receptor agonist tanaproget

  • J Med Chem. 2005 Aug 11;48(16):5092-5. doi: 10.1021/jm050358b.
Andrew Fensome  1 ,  Reinhold Bender ,  Rajiv Chopra ,  Jeff Cohen ,  Mark A Collins ,  Valerie Hudak ,  Karl Malakian ,  Susan Lockhead ,  Andrea Olland ,  Kristine Svenson ,  Eugene A Terefenko ,  Ray J Unwalla ,  James M Wilhelm ,  Scott Wolfrom ,  Yuan Zhu ,  Zhiming Zhang ,  Puwen Zhang ,  Richard C Winneker ,  Jay Wrobel
Affiliations
  • 1. Chemical and Screening Sciences, Women's Health Research Institute, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. [email protected]
PMID: 16078826 DOI: 10.1021/jm050358b
Abstract

Tanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives. Additional SAR, biological activity, and structural information from a tanaproget/hPR-LBD (hPR-LBD = human Progesterone Receptor ligand binding domain) cocrystal structure will also be presented.