title: Discovery of non-steroidal mifepristone mimetics: pyrazoline-based PR antagonists.
abstract: Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-endometriotic activities. Non-steroidal mimetics of mifepristone and progesterone are important templates for modulation of the progesterone receptor (PR). For our PR program, we sought an unexplored, synthetically accessible non-steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. Docking of compounds into a PR homology model identified 4-substituted pyrazolines, which, when synthesized and tested, exhibited functional antagonism of PR.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709-3398, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Jones
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Stewart
authors.forename: Robert A
authors.initials: RA
authors.lastname: Noe
authors.forename: Lara S
authors.initials: LS
authors.lastname: Kallander
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Madauss
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Williams
authors.forename: Scott K
authors.initials: SK
authors.lastname: Thompson
authors.forename: David W
authors.initials: DW
authors.lastname: Gray
authors.forename: William J
authors.initials: WJ
authors.lastname: Hoekstra
mesh_terms: D002460:Cell Line; D005456:Fluorescent Dyes; D006801:Humans; D008024:Ligands; D015735:Mifepristone / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D011720:Pyrazoles; D011980:Receptors, Progesterone; D015735:Mifepristone