Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK. Hom, R. K., Bowers, S., Sealy, J. M., Truong, A. P., Probst, G. D., Neitzel, M. L., Neitz, R. J., Fang, L., Brogley, L., Wu, J., Konradi, A. W., Sham, H. L., Tóth, G., Pan, H., Yao, N., Artis, D. R., Quinn, K., Sauer, J., Powell, K., Ren, Z., Bard, F., Yednock, T. A., & Griswold-Prenner, I. Bioorganic & Medicinal Chemistry Letters, 20(24):7303–7307, December, 2010. doi abstract bibtex From high throughput screening, we discovered compound 1, the prototype for a series of disubstituted thiophene inhibitors of JNK which is selective towards closely related MAP kinases p38 and Erk2. Herein we describe the evolution of these compounds to a novel class of thiophene and thiazole JNK inhibitors that retain favorable solubility, permeability, and P-gp properties for development as CNS agents for treatment of neurodegeneration. Compound 61 demonstrated JNK3 IC(50)=77 nM and retained the excellent broad kinase selectivity observed for the series.
@article{hom_design_2010,
title = {Design and synthesis of disubstituted thiophene and thiazole based inhibitors of {JNK}},
volume = {20},
issn = {1464-3405},
doi = {10.1016/j.bmcl.2010.10.066},
abstract = {From high throughput screening, we discovered compound 1, the prototype for a series of disubstituted thiophene inhibitors of JNK which is selective towards closely related MAP kinases p38 and Erk2. Herein we describe the evolution of these compounds to a novel class of thiophene and thiazole JNK inhibitors that retain favorable solubility, permeability, and P-gp properties for development as CNS agents for treatment of neurodegeneration. Compound 61 demonstrated JNK3 IC(50)=77 nM and retained the excellent broad kinase selectivity observed for the series.},
language = {eng},
number = {24},
journal = {Bioorganic \& Medicinal Chemistry Letters},
author = {Hom, Roy K. and Bowers, Simeon and Sealy, Jennifer M. and Truong, Anh P. and Probst, Gary D. and Neitzel, Martin L. and Neitz, R. Jeffrey and Fang, Larry and Brogley, Louis and Wu, Jing and Konradi, Andrei W. and Sham, Hing L. and Tóth, Gergely and Pan, Hu and Yao, Nanhua and Artis, Dean R. and Quinn, Kevin and Sauer, John-Michael and Powell, Kyle and Ren, Zhao and Bard, Frédérique and Yednock, Ted A. and Griswold-Prenner, Irene},
month = dec,
year = {2010},
pmid = {21071223},
keywords = {Animals, Drug Design, Humans, JNK Mitogen-Activated Protein Kinases, Mice, Microsomes, Liver, Mitogen-Activated Protein Kinase 10, Mitogen-Activated Protein Kinase 8, Protein Kinase Inhibitors, Quinolines, Structure-Activity Relationship, Thiazoles, Thiophenes},
pages = {7303--7307},
}
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