89533-28-8Relevant academic research and scientific papers
Pyridopyrimidinone derivatives as potent and selective c-jun N-terminal kinase (JNK) inhibitors
Zheng, Ke,Park, Chul Min,Iqbal, Sarah,Hernandez, Pamela,Park, Hajeung,Lograsso, Philip V.,Feng, Yangbo
supporting information, p. 413 - 418 (2015/04/27)
A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure-activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 μM), had high potency in functional cell based assays, and had high stability in human liver microsome (t1/2 = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 ?. These structures elucidated the binding mode (Type-I binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.
NOVEL COMPOUNDS AS JNK KINASE INHIBITORS
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Page/Page column 93, (2015/06/18)
The present invention is directed to modulators, such as inhibitors, of JNK isoform 2 (JNK2) or isoform 3 (JNK3) comprising compounds of formula (I) or formula (II) as described herein. Compounds of the invention can be used for treatment of a medical dis
