1,3-Diaxially substituted trans-decalins: potential nonsteroidal human progesterone receptor inhibitors.
On the basis of molecular modeling and QSAR analysis of the known human progesterone receptor (hPR) inhibitor Mifepristone (RU-486) and other hPR ligands, a new class of potential nonsteroidal hPR inhibitors was designed. The parent racemic compound 1 was synthesized through an efficient 13-step synthetic pathway. The key constructive steps are a stereoselective epoxide ring opening and the reductive Heck cyclization to form the main framework of (+/-)-1. The current established flexible synthetic route allows for further chemical diversification.
Li
Ze
Z
Department of Medicinal Chemistry, The University of Mississippi, P.O. Box 1848, University, Mississippi 38677, USA.
Watkins
E Blake
EB
Liu
Hua
H
Chittiboyina
Amar G
AG
Carvalho
Paulo B
PB
Avery
Mitchell A
MA
D003500:Cyclization; D004852:Epoxy Compounds; D006801:Humans; D008024:Ligands; D015735:Mifepristone; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D004852:Epoxy Compounds; D008024:Ligands; D009281:Naphthalenes; D011980:Receptors, Progesterone; D015735:Mifepristone; C007229:decalin