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

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Thompson SK,Washburn DG,Frazee JS,Madauss KP,Hoang TH,Lapinski L,Grygielko ET,Glace LE,Trizna W,Williams SP,Duraiswami C,Bray JD,Laping NJ

doi

10.1016/j.bmcl.2009.06.055

subject

Has Abstract

pub_date

2009-08-15 00:00:00

pages

4777-80

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00883-X

journal_volume

19

pub_type

杂志文章

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