Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors.
A novel series of c-jun N-terminal kinase (JNK) inhibitors were designed and developed from a high-throughput-screening hit. Through the optimization of the piperazine amide 1, several potent compounds were discovered. The X-ray crystal structure of 4g showed a unique binding mode different from other well known JNK3 inhibitors.
Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
Youseung
Y
Shin
Weiming
W
Chen
Jeff
J
Habel
Derek
D
Duckett
Yuan Yuan
YY
Ling
Marcel
M
Koenig
Yuanjun
Y
He
Tomas
T
Vojkovsky
Philip
P
LoGrasso
Theodore M
TM
Kamenecka
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases