Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors.
A series of thiadiazole derivatives has been designed as potential allosteric, substrate competitive inhibitors of the protein kinase JNK. We report on the synthesis, characterization and evaluation of a series of compounds that resulted in the identification of potent and selective JNK inhibitors targeting its JIP-1 docking site.
De
Surya K
SK
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Chen
Vida
V
Stebbins
John L
JL
Chen
Li-Hsing
LH
Cellitti
Jason F
JF
Machleidt
Thomas
T
Barile
Elisa
E
Riel-Mehan
Megan
M
Dahl
Russell
R
Yang
Li
L
Emdadi
Aras
A
Murphy
Ria
R
Pellecchia
Maurizio
M
D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D013830:Thiadiazoles; D048031:JNK Mitogen-Activated Protein Kinases