Structure-driven HtL: design and synthesis of novel aminoindazole inhibitors of c-Jun N-terminal kinase activity.
The design and synthesis of a new series of c-Jun N-terminal kinase inhibitors are reported. The novel series of substituted amino indazoles were designed based on a combination of hits from high-throughput screening and X-ray crystal structure information of the compounds crystallised into the JNK-1 ATP binding site.
Stocks
Michael J
MJ
Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. mike.stocks@astrazeneca.com
Barber
Simon
S
Ford
Rhonan
R
Leroux
Frederic
F
St-Gallay
Steve
S
Teague
Simon
S
Xue
Yafeng
Y
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007191:Indazoles; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8