Synthesis and PKCtheta inhibitory activity of a series of 4-indolylamino-5-phenyl-3-pyridinecarbonitriles.
A series of 4-indolylamino-5-phenyl-3-pyridinecarbonitrile inhibitors of PKCtheta were synthesized as potential anti-inflammatory agents. The effects of specific substitution on the 5-phenyl moiety and variations of the positional isomers of the 4-indolylamino substituent were explored. This study led to the discovery of compound 12d, which had an IC(50) value of 18nM for the inhibition of PKCtheta.
Dushin
Russell G
RG
Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA.
Nittoli
Thomas
T
Ingalls
Charles
C
Boschelli
Diane H
DH
Cole
Derek C
DC
Wissner
Allan
A
Lee
Julie
J
Yang
Xiaoke
X
Morgan
Paul
P
Brennan
Agnes
A
Chaudhary
Divya
D
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D000255:Adenosine Triphosphate; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta