Jun N-terminal Kinase Inhibitors

Rech JC, Yato M, Duckett D, Ember B, LoGrasso PV, Bergman RG, Ellman JA (2007) Synthesis of potent bicyclic bisarylimidazole c-Jun N-terminal kinase inhibitors by catalytic C-H bond activation. J Am Chem Soc 129 490-491... 

Furthermore, an N-heteroqrclic carbene (NHC) complex formed by stoichiometric reaction of a benzimidazole substrate with [RhCl(coe)2]2 in the presence of PCyj was characterized by X-ray crystallography and was proposed to be the catalyst resting state [123]. Similar intermediates have been characterized in the rhodium-catalyzed alkylation of N-methylbenzimidazoles [124], 3,4-dihydroquinazolines [125], and l,4-benzodiazepine-2-ones [126]. This methodology was later extended to the synthesis ofc-Jun N-terminal kinase inhibitors [127]. 

Huang, C., Ma, W. Y.,Ryan, C. A., Dong,Z. (1997). Proteinase inhibitors I and II from potatoes speeifieally bloek UV-indueed activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase. Proc. Natl. Acad. Sci. U. S. A., 94, 11957-11962. 

Zhuang, Z. Y., Wen, Y. R., Zhang, D. R., Borsello, T., Bonny, C., Strichartz, G. R., Decosterd, I., and Ji, R. R. (2006). A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation Respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance.. Neurosci. 26, 3551 -3560. 

FFA, free fatty acid GH, growth hormone GLP-1, glucagon-like protein 1 GS, glycogen synthase GSK3, glycogen synthase kinase 3 HDL, high density lipoprotein HF, heart failure IKK, inhibitor of kappa B kinase INK, c-jun N-terminal kinase EDL, low density lipoprotein Ep(a), lipoprotein little a EV, left ventricular MetS, metabolic syndrome MI, myocardial infarction... 

INK (c-Jun N-terminal kinase) was first identified as the UV-induced activity responsible for phosphorylating, and thereby activating the proto-oncogene c-Jun (5). At the same time, they were found as SAPKs (stress-activated protein kinases), which are proline-directed kinases activated by growth factors and biosynthetic inhibitors such as anisomycin. Common stimuli that activate JNKs include inflammatory cytokines fatty acids and environmental stresses such as UV, osmotic shock, heat... 

Saporito MS, Brown EM, Miller MS, Carswell S (1999) CEP 1347/ KT 7515, an inhibitor of c-jun N terminal kinase activation, attenuates the 1 methyl 4 phenyl tetrahyopyridine mediated loss of nigrostriatal dopaminergic neurons in vivo. J Pharmocol Exp Ther 288 421 27. 

Antisense oligonucleotides (Tau genetic ablation) c-Jun N-terminal kinase (JNKs) inhibitors Harmine (P-carboline alkaloid)... 

Ijjaali, I., Petitet, F., Dubus, E., Barberan, O. and Michel, A. (2007) Assessing potency of c-Jun N-terminal kinase 3 (JNK3) inhibitors using 2D molecular descriptors and binary QSAR methodology. Bioorg. Med. Chem., 15, 4256-4264. 

M. H., et al. (2004) Identification of Potent Inhibitors of c-Jun N-terminal Kinase-1 (JNK1) using Ultra High-Throughput Affinity Based Screening. 12th Symposium on Second Messengers and Phospho-pro-teins (SMP-2004). 

A potent inhibitor of the serine/threonine Jun N-terminal Kinase 3 (JNK3) was identified after using a fragment-based NMR approach. A follow-up study with competition-binding methods and molecular docking based on the crystal structure of JNK3 proposed potential binding models. These models were used in turn to synthesize a set of several thousand optimized compounds... 

Shin Y, Chen W, Habel J, Duckett D, Ling YY, Koenig M, He Y, Vojkovsky T, LoGrasso P, Kamenecka TM (2009) Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors. Bioorg Med Chem Lett 19 3344-3347... 

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