2-Amino-9-aryl-3-cyano-4-methyl-7-oxo-6,7,8,9-tetrahydropyrido[2',3':4,5]thieno[2,3-b]pyridine derivatives as selective progesterone receptor agonists

Yonghui Wang; Chaya Duraiswami; Kevin P Madauss; Thuy B Tran; Shawn P Williams; Su-Jun Deng; Todd L Graybill; Marlys Hammond; David G Jones; Eugene T Grygielko; Jeffrey D Bray; Scott K Thompson

doi:10.1016/j.bmcl.2009.07.100

2-Amino-9-aryl-3-cyano-4-methyl-7-oxo-6,7,8,9-tetrahydropyrido[2',3':4,5]thieno[2,3-b]pyridine derivatives as selective progesterone receptor agonists

Bioorg Med Chem Lett. 2009 Sep 1;19(17):4916-9. doi: 10.1016/j.bmcl.2009.07.100. Epub 2009 Jul 23.

Authors

Yonghui Wang¹, Chaya Duraiswami, Kevin P Madauss, Thuy B Tran, Shawn P Williams, Su-Jun Deng, Todd L Graybill, Marlys Hammond, David G Jones, Eugene T Grygielko, Jeffrey D Bray, Scott K Thompson

Affiliation

¹ Research & Development, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. [email protected]

PMID: 19664922
DOI: 10.1016/j.bmcl.2009.07.100

Abstract

High throughput screening of the corporate compound collection led to the identification of a novel series of 2-amino-9-aryl-3-cyano-4-methyl-7-oxo-6,7,8,9-tetrahydropyrido[2',3':4,5]thieno[2,3-b]pyridine derivatives as selective PR agonists. Initial SAR exploration leading to potent and selective agonists 9 and 11, X-ray crystal structure of 9 bound to PR-LBD and preliminary developability data are described.

MeSH terms

Animals
Binding Sites
Computer Simulation
Crystallography, X-Ray
Humans
Microsomes, Liver / metabolism
Molecular Conformation
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Pyridones / chemical synthesis
Pyridones / chemistry*
Pyridones / pharmacology
Rats
Receptors, Progesterone / agonists*
Receptors, Progesterone / metabolism
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology

Substances

Pyridines
Pyridones
Receptors, Progesterone
Thiophenes