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.
Journal of medicinal chemistry 2005 Aug 11; 48(16):5092-5
Fensome A A, Bender R R, Chopra R R, Cohen J J, Collins M MA, Hudak V V, Malakian K K, Lockhead S S, Olland A A, Svenson K K, Terefenko E EA, Unwalla R RJ, Wilhelm J JM, Wolfrom S S, Zhu Y Y, Zhang Z Z, Zhang P P, Winneker R RC, Wrobel J J
Chemical and Screening Sciences, Women's Health Research Institute, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. fensoma@wyeth.com
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.