title: 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.
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.
authors.affiliation: Chemical and Screening Sciences, Women's Health Research Institute, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. fensoma@wyeth.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Fensome
authors.forename: Reinhold
authors.initials: R
authors.lastname: Bender
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chopra
authors.forename: Jeff
authors.initials: J
authors.lastname: Cohen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Collins
authors.forename: Valerie
authors.initials: V
authors.lastname: Hudak
authors.forename: Karl
authors.initials: K
authors.lastname: Malakian
authors.forename: Susan
authors.initials: S
authors.lastname: Lockhead
authors.forename: Andrea
authors.initials: A
authors.lastname: Olland
authors.forename: Kristine
authors.initials: K
authors.lastname: Svenson
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Terefenko
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Unwalla
authors.forename: James M
authors.initials: JM
authors.lastname: Wilhelm
authors.forename: Scott
authors.initials: S
authors.lastname: Wolfrom
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Puwen
authors.initials: P
authors.lastname: Zhang
authors.forename: Richard C
authors.initials: RC
authors.lastname: Winneker
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D003271:Contraceptive Agents, Female / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000737:chemistry; D013329:Structure-Activity Relationship; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D048588:Benzoxazines; D003271:Contraceptive Agents, Female; D008024:Ligands; D010078:Oxazines; D011758:Pyrroles; D011980:Receptors, Progesterone; D013871:Thiones; C503890:tanoproget; D000469:Alkaline Phosphatase