First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors.
A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCtheta inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCtheta inhibitor with good selectivity over PKCdelta.
Niu
Chuansheng
C
Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA. niuc@wyeth.com
Boschelli
Diane H
DH
Tumey
L Nathan
LN
Bhagirath
Niala
N
Subrath
Joan
J
Shim
Jaechul
J
Wang
Yan
Y
Wu
Biqi
B
Eid
Clark
C
Lee
Julie
J
Yang
Xiaoke
X
Brennan
Agnes
A
Chaudhary
Divya
D
D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta