2-Alkenylthieno[2,3-b]pyridine-5-carbonitriles: Potent and selective inhibitors of PKCtheta.
A series of 2-alkenyl thieno[2,3-b]pyridine inhibitors of PKCtheta were synthesized as potential inflammatory modulators. This series led to the discovery of 2-alkenyl amides, which are exceptionally potent and selective inhibitors of PKCtheta. Compound 8 has an IC(50) of 3.8nM against PKCtheta and shows excellent selectivity over a variety of PKC isoforms.
Nathan Tumey
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Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA. nathantumey@yahoo.com
Boschelli
Diane H
DH
Lee
Julie
J
Chaudhary
Divya
D
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007527:Isoenzymes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D013876:Thiophenes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta