The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor

John Hynes; Hong Wu; Sidney Pitt; Ding Ren Shen; Rosemary Zhang; Gary L. Schieven; Kathleen M. Gillooly; David J. Shuster; Tracy L. Taylor; Xiao Xia Yang; Kim W. McIntyre; Murray McKinnon; Hongjian Zhang; Punit H. Marathe; Arthur M. Doweyko; Kevin Kish; Susan E. Kiefer; John S. Sack; John A. Newitt; Joel C. Barrish; John Dodd; Katerina Leftheris

doi:10.1016/j.bmcl.2008.02.031

The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor

John Hynes, Hong Wu, Sidney Pitt, Ding Ren Shen, Rosemary Zhang, Gary L. Schieven, Kathleen M. Gillooly, David J. Shuster, Tracy L. Taylor, Xiao Xia Yang, Kim W. McIntyre, Murray McKinnon, Hongjian Zhang, Punit H. Marathe, Arthur M. Doweyko, Kevin Kish, Susan E. Kiefer, John S. Sack, John A. Newitt, Joel C. BarrishJohn Dodd, Katerina Leftheris

Chemistry

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27 Scopus citations

Abstract

A novel structural class of p38α MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38α inhibitor that is orally efficacious in rodent models of acute and chronic inflammation.

Original language	English (US)
Pages (from-to)	1762-1767
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2008.02.031
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.2008.02.031

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Hynes, J., Wu, H., Pitt, S., Shen, D. R., Zhang, R., Schieven, G. L., Gillooly, K. M., Shuster, D. J., Taylor, T. L., Yang, X. X., McIntyre, K. W., McKinnon, M., Zhang, H., Marathe, P. H., Doweyko, A. M., Kish, K., Kiefer, S. E., Sack, J. S., Newitt, J. A., ... Leftheris, K. (2008). The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor. Bioorganic and Medicinal Chemistry Letters, 18(6), 1762-1767. https://doi.org/10.1016/j.bmcl.2008.02.031

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title = "The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor",

abstract = "A novel structural class of p38α MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38α inhibitor that is orally efficacious in rodent models of acute and chronic inflammation.",

author = "John Hynes and Hong Wu and Sidney Pitt and Shen, \{Ding Ren\} and Rosemary Zhang and Schieven, \{Gary L.\} and Gillooly, \{Kathleen M.\} and Shuster, \{David J.\} and Taylor, \{Tracy L.\} and Yang, \{Xiao Xia\} and McIntyre, \{Kim W.\} and Murray McKinnon and Hongjian Zhang and Marathe, \{Punit H.\} and Doweyko, \{Arthur M.\} and Kevin Kish and Kiefer, \{Susan E.\} and Sack, \{John S.\} and Newitt, \{John A.\} and Barrish, \{Joel C.\} and John Dodd and Katerina Leftheris",

year = "2008",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2008.02.031",

language = "English (US)",

volume = "18",

pages = "1762--1767",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "6",

}

Hynes, J, Wu, H, Pitt, S, Shen, DR, Zhang, R, Schieven, GL, Gillooly, KM, Shuster, DJ, Taylor, TL, Yang, XX, McIntyre, KW, McKinnon, M, Zhang, H, Marathe, PH, Doweyko, AM, Kish, K, Kiefer, SE, Sack, JS, Newitt, JA, Barrish, JC, Dodd, J & Leftheris, K 2008, 'The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 6, pp. 1762-1767. https://doi.org/10.1016/j.bmcl.2008.02.031

The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor. / Hynes, John; Wu, Hong; Pitt, Sidney et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 6, 15.03.2008, p. 1762-1767.

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

TY - JOUR

T1 - The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor

AU - Hynes, John

AU - Wu, Hong

AU - Pitt, Sidney

AU - Shen, Ding Ren

AU - Zhang, Rosemary

AU - Schieven, Gary L.

AU - Gillooly, Kathleen M.

AU - Shuster, David J.

AU - Taylor, Tracy L.

AU - Yang, Xiao Xia

AU - McIntyre, Kim W.

AU - McKinnon, Murray

AU - Zhang, Hongjian

AU - Marathe, Punit H.

AU - Doweyko, Arthur M.

AU - Kish, Kevin

AU - Kiefer, Susan E.

AU - Sack, John S.

AU - Newitt, John A.

AU - Barrish, Joel C.

AU - Dodd, John

AU - Leftheris, Katerina

PY - 2008/3/15

Y1 - 2008/3/15

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AB - A novel structural class of p38α MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38α inhibitor that is orally efficacious in rodent models of acute and chronic inflammation.

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ER -

The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38α MAP kinase inhibitor

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