Second generation 4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno[2,3-b]pyridine-5-carbonitrile PKCtheta inhibitors.
Thieno[2,3-b]pyridine-5-carbonitrile 16 with a 4-methyl-5-indolylamine at C-4 and a 5-methoxy-2-(dimethylamino)-methylphenyl group at C-2 had an IC(50) value of 16 nM for the inhibition of PKCtheta. While moderate inhibition of PKCdelta was also observed (IC(50)=130 nM), 16 had IC(50) values of greater than 5 microM against Lyn and other members of the Src kinase family.
Wu
Biqi
B
Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA.
Boschelli
Diane H
DH
Lee
Julie
J
Yang
Xiaoke
X
Chaudhary
Divya
D
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008956:Models, Chemical; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000074121:Protein Kinase C-theta; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C539891:4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno(2,3-b)pyridine-5-carbonitrile; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D009570:Nitriles; D011725:Pyridines; D019061:src-Family Kinases; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta