Synthesis and PKCtheta inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles.
A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCtheta inhibitors. Optimization resulted in the identification of compound 15 with an IC(50) value 0.44 nM for the inhibition of PKCtheta with 150-fold selectivity over PKCdelta.
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. shimj@wyeth.com
Jaechul
J
Shim
Clark
C
Eid
Julie
J
Lee
Erica
E
Liu
Divya
D
Chaudhary
Diane H
DH
Boschelli
D015195:Drug Design; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013449:Sulfonamides; D011493:Protein Kinase C