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.
Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA.
Russell G
RG
Dushin
Thomas
T
Nittoli
Charles
C
Ingalls
Diane H
DH
Boschelli
Derek C
DC
Cole
Allan
A
Wissner
Julie
J
Lee
Xiaoke
X
Yang
Paul
P
Morgan
Agnes
A
Brennan
Divya
D
Chaudhary
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