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. Barrish

John Dodd, Katerina Leftheris

Chemistry

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

29 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",

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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

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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

Abstract

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