Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies.
A new series of 4-anilinopyrimidines has been synthesized and evaluated as JNK1 inhibitors. SAR studies led to the discovery of potent JNK1 inhibitors with good enzymatic activity as well as cellular potency represented by compound 2b. Kinase selectivity profile and the crystal structure of 2b are also described.
Liu
Mei
M
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. mei.liu@abbott.com
Wang
Sanyi
S
Clampit
Jill E
JE
Gum
Rebecca J
RJ
Haasch
Deanna L
DL
Rondinone
Cristina M
CM
Trevillyan
James M
JM
Abad-Zapatero
Cele
C
Fry
Elizabeth H
EH
Sham
Hing L
HL
Liu
Gang
G
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011743:Pyrimidines; D048031:JNK Mitogen-Activated Protein Kinases