Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors

Stephen T. Wrobleski; Shuqun Lin; John Hynes; Hong Wu; Sidney Pitt; Ding Ren Shen; Rosemary Zhang; Kathleen M. Gillooly; David J. Shuster; Kim W. McIntyre; Arthur M. Doweyko; Kevin F. Kish; Jeffrey A. Tredup; Gerald J. Duke; John S. Sack; Murray McKinnon; John Dodd; Joel C. Barrish; Gary L. Schieven; Katerina Leftheris

doi:10.1016/j.bmcl.2008.02.067

Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors

Stephen T. Wrobleski
, Shuqun Lin
, John Hynes
, Hong Wu
, Sidney Pitt
, Ding Ren Shen
, Rosemary Zhang
, Kathleen M. Gillooly
, David J. Shuster
, Kim W. McIntyre
, Arthur M. Doweyko
, Kevin F. Kish
, Jeffrey A. Tredup
, Gerald J. Duke
, John S. Sack
, Murray McKinnon
, John Dodd
, Joel C. Barrish
, Gary L. Schieven
, Katerina Leftheris

Chemistry

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

39 Scopus citations

Abstract

A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38α MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38α enzyme.

Original language	English (US)
Pages (from-to)	2739-2744
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2008.02.067
State	Published - Apr 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.2008.02.067

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Wrobleski, S. T., Lin, S., Hynes, J., Wu, H., Pitt, S., Shen, D. R., Zhang, R., Gillooly, K. M., Shuster, D. J., McIntyre, K. W., Doweyko, A. M., Kish, K. F., Tredup, J. A., Duke, G. J., Sack, J. S., McKinnon, M., Dodd, J., Barrish, J. C., Schieven, G. L., & Leftheris, K. (2008). Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors. Bioorganic and Medicinal Chemistry Letters, 18(8), 2739-2744. https://doi.org/10.1016/j.bmcl.2008.02.067

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title = "Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors",

abstract = "A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38α MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38α enzyme.",

author = "Wrobleski, \{Stephen T.\} and Shuqun Lin and John Hynes and Hong Wu and Sidney Pitt and Shen, \{Ding Ren\} and Rosemary Zhang and Gillooly, \{Kathleen M.\} and Shuster, \{David J.\} and McIntyre, \{Kim W.\} and Doweyko, \{Arthur M.\} and Kish, \{Kevin F.\} and Tredup, \{Jeffrey A.\} and Duke, \{Gerald J.\} and Sack, \{John S.\} and Murray McKinnon and John Dodd and Barrish, \{Joel C.\} and Schieven, \{Gary L.\} and Katerina Leftheris",

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doi = "10.1016/j.bmcl.2008.02.067",

language = "English (US)",

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Wrobleski, ST, Lin, S, Hynes, J, Wu, H, Pitt, S, Shen, DR, Zhang, R, Gillooly, KM, Shuster, DJ, McIntyre, KW, Doweyko, AM, Kish, KF, Tredup, JA, Duke, GJ, Sack, JS, McKinnon, M, Dodd, J, Barrish, JC, Schieven, GL & Leftheris, K 2008, 'Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 8, pp. 2739-2744. https://doi.org/10.1016/j.bmcl.2008.02.067

TY - JOUR

T1 - Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors

AU - Wrobleski, Stephen T.

AU - Lin, Shuqun

AU - Hynes, John

AU - Wu, Hong

AU - Pitt, Sidney

AU - Shen, Ding Ren

AU - Zhang, Rosemary

AU - Gillooly, Kathleen M.

AU - Shuster, David J.

AU - McIntyre, Kim W.

AU - Doweyko, Arthur M.

AU - Kish, Kevin F.

AU - Tredup, Jeffrey A.

AU - Duke, Gerald J.

AU - Sack, John S.

AU - McKinnon, Murray

AU - Dodd, John

AU - Barrish, Joel C.

AU - Schieven, Gary L.

AU - Leftheris, Katerina

PY - 2008/4/15

Y1 - 2008/4/15

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AB - A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38α MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38α enzyme.

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UR - https://www.scopus.com/pages/publications/41849106872#tab=citedBy

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AN - SCOPUS:41849106872

SN - 0960-894X

VL - 18

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 8

ER -

Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors

Abstract

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