title: 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.
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.
authors: Research & Development, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. yonghui.2.wang@gsk.com
authors: Yonghui
authors: Y
authors: Wang
authors: Chaya
authors: C
authors: Duraiswami
authors: Kevin P
authors: KP
authors: Madauss
authors: Thuy B
authors: TB
authors: Tran
authors: Shawn P
authors: SP
authors: Williams
authors: Su-Jun
authors: SJ
authors: Deng
authors: Todd L
authors: TL
authors: Graybill
authors: Marlys
authors: M
authors: Hammond
authors: David G
authors: DG
authors: Jones
authors: Eugene T
authors: ET
authors: Grygielko
authors: Jeffrey D
authors: JD
authors: Bray
authors: Scott K
authors: SK
authors: Thompson
mesh_terms: 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
chemical_list: D011725:Pyridines; D011728:Pyridones; D011980:Receptors, Progesterone; D013876:Thiophenes