Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

Journal Article · Fri Sep 03 04:00:00 EDT 2010 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmcl.2009.06.055· OSTI ID:1006164

Thompson, Scott K; Washburn, David G; Frazee, James S; Madauss, Kevin P; Hoang, Tram H; Lapinski, Leahann; Grygielko, Eugene T; Glace, Lindsay E; Trizna, Walter; Williams, Shawn P; Duraiswami, Chaya; Bray, Jeffrey D; Laping, Nicholas J

Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1006164
• Journal Information: Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (16) ; 08, 2009 Vol. 19; ISSN 0960-894X
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DESIGN
ESTROGENS
PROGESTERONE
PYRROLIDINES