Design and synthesis of 2'-anilino-4,4'-bipyridines as selective inhibitors of c-Jun N-terminal kinase-3.
The design and synthesis of a new series of c-Jun N-terminal kinase-3 (JNK3) inhibitors with selectivity against JNK1 are reported. The novel series of substituted 2'-anilino-4,4'-bipyridines were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of compounds crystallized into the JNK3 ATP binding active site.
Swahn
Britt-Marie
BM
Department of Medicinal Chemistry, AstraZeneca R&D Södertälje, S-151 85, Södertälje, Sweden. britt-marie.swahn@astrazeneca.com
Xue
Yafeng
Y
Arzel
Erwan
E
Kallin
Elisabet
E
Magnus
Angelika
A
Plobeck
Niklas
N
Viklund
Jenny
J
D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D018360:Crystallography, X-Ray; D015195:Drug Design; D020128:Inhibitory Concentration 50; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D011725:Pyridines; D048057:Mitogen-Activated Protein Kinase 10; C023650:aniline