Discovery of Potent, Highly Selective, and Orally Bioavailable Pyridine Carboxamide c-Jun NH<sub>2</sub>-Terminal Kinase Inhibitors
Hongyu Zhao(Abbott Fund), Michael D. Serby(Abbott Fund), Zhili Xin(Abbott Fund), Bruce G. Szczepankiewicz(Abbott Fund), Mei Liu(Abbott Fund), Christi Kosogof(Abbott Fund), Bo Liu(Abbott Fund), Lissa T.J. Nelson(Abbott Fund), Eric F. Johnson(Abbott Fund), Sanyi Wang(Abbott Fund), Terry M. Pederson(Abbott Fund), Rebecca J. Gum(Abbott Fund), Jill E. Clampit(Abbott Fund), Deanna L. Haasch(Abbott Fund), Cele Abad‐Zapatero(Abbott Fund), Elizabeth H. Fry(Abbott Fund), Cristina M. Rondinone(Abbott Fund), James M. Trevillyan(Abbott Fund), Hing L. Sham(Abbott Fund), Gang Liu(Abbott Fund)
Cited by 75Open Access
Abstract
C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.
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