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.
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.
Wang
Yonghui
Y
Research & Development, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. yonghui.2.wang@gsk.com
Duraiswami
Chaya
C
Madauss
Kevin P
KP
Tran
Thuy B
TB
Williams
Shawn P
SP
Deng
Su-Jun
SJ
Graybill
Todd L
TL
Hammond
Marlys
M
Jones
David G
DG
Grygielko
Eugene T
ET
Bray
Jeffrey D
JD
Thompson
Scott K
SK
D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D011725:Pyridines; D011728:Pyridones; D011980:Receptors, Progesterone; D013876:Thiophenes