Discovery of non-steroidal mifepristone mimetics: pyrazoline-based PR antagonists

TY - JOUR

T1 - Discovery of non-steroidal mifepristone mimetics

T2 - pyrazoline-based PR antagonists

AU - Jones, David G.

AU - Liang, Xi

AU - Stewart, Eugene L.

AU - Noe, Robert A.

AU - Kallander, Lara S.

AU - Madauss, Kevin P.

AU - Williams, Shawn P.

AU - Thompson, Scott K.

AU - Gray, David W.

AU - Hoekstra, William J.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1016/j.bmcl.2005.05.001

DO - 10.1016/j.bmcl.2005.05.001

M3 - Article

C2 - 15925510

SN - 0960-894X

VL - 15

SP - 3203

EP - 3206

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 13

ER -