Benzothiazole based inhibitors of p38α MAP kinase

Chunjian Liu; James Lin; Sidney Pitt; Rosemary F. Zhang; John S. Sack; Susan E. Kiefer; Kevin Kish; Arthur M. Doweyko; Hongjian Zhang; Punit H. Marathe; James Trzaskos; Murray Mckinnon; John H. Dodd; Joel C. Barrish; Gary L. Schieven; Katerina Leftheris

doi:10.1016/j.bmcl.2008.02.011

Benzothiazole based inhibitors of p38α MAP kinase

Chunjian Liu, James Lin, Sidney Pitt, Rosemary F. Zhang, John S. Sack, Susan E. Kiefer, Kevin Kish, Arthur M. Doweyko, Hongjian Zhang, Punit H. Marathe, James Trzaskos, Murray Mckinnon, John H. Dodd, Joel C. Barrish, Gary L. Schieven, Katerina Leftheris

Chemistry

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38α inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38α enzyme.

Original language	English (US)
Pages (from-to)	1874-1879
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2008.02.011
State	Published - Mar 15 2008

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2008.02.011

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Liu, C., Lin, J., Pitt, S., Zhang, R. F., Sack, J. S., Kiefer, S. E., Kish, K., Doweyko, A. M., Zhang, H., Marathe, P. H., Trzaskos, J., Mckinnon, M., Dodd, J. H., Barrish, J. C., Schieven, G. L., & Leftheris, K. (2008). Benzothiazole based inhibitors of p38α MAP kinase. Bioorganic and Medicinal Chemistry Letters, 18(6), 1874-1879. https://doi.org/10.1016/j.bmcl.2008.02.011

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abstract = "Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38α inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38α enzyme.",

author = "Chunjian Liu and James Lin and Sidney Pitt and Zhang, {Rosemary F.} and Sack, {John S.} and Kiefer, {Susan E.} and Kevin Kish and Doweyko, {Arthur M.} and Hongjian Zhang and Marathe, {Punit H.} and James Trzaskos and Murray Mckinnon and Dodd, {John H.} and Barrish, {Joel C.} and Schieven, {Gary L.} and Katerina Leftheris",

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AU - Liu, Chunjian

AU - Lin, James

AU - Pitt, Sidney

AU - Zhang, Rosemary F.

AU - Sack, John S.

AU - Kiefer, Susan E.

AU - Kish, Kevin

AU - Doweyko, Arthur M.

AU - Zhang, Hongjian

AU - Marathe, Punit H.

AU - Trzaskos, James

AU - Mckinnon, Murray

AU - Dodd, John H.

AU - Barrish, Joel C.

AU - Schieven, Gary L.

AU - Leftheris, Katerina

PY - 2008/3/15

Y1 - 2008/3/15

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AB - Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38α inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38α enzyme.

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JO - Bioorganic and Medicinal Chemistry Letters

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ER -

Benzothiazole based inhibitors of p38α MAP kinase

Abstract

All Science Journal Classification (ASJC) codes

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