Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

T. G. Murali Dhar; Stephen T. Wrobleski; Shuqun Lin; Joseph A. Furch; David S. Nirschl; Yi Fan; Gordon Todderud; Sidney Pitt; Arthur M. Doweyko; John S. Sack; Arvind Mathur; Murray McKinnon; Joel C. Barrish; John H. Dodd; Gary L. Schieven; Katerina Leftheris

doi:10.1016/j.bmcl.2007.07.029

Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

T. G. Murali Dhar
, Stephen T. Wrobleski
, Shuqun Lin
, Joseph A. Furch
, David S. Nirschl
, Yi Fan
, Gordon Todderud
, Sidney Pitt
, Arthur M. Doweyko
, John S. Sack
, Arvind Mathur
, Murray McKinnon
, Joel C. Barrish
, John H. Dodd
, Gary L. Schieven
, Katerina Leftheris

Chemistry

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

26 Scopus citations

Abstract

The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.

Original language	English (US)
Pages (from-to)	5019-5024
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2007.07.029
State	Published - Sep 15 2007

All Science Journal Classification (ASJC) codes

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

Access to Document

10.1016/j.bmcl.2007.07.029

Cite this

Murali Dhar, T. G., Wrobleski, S. T., Lin, S., Furch, J. A., Nirschl, D. S., Fan, Y., Todderud, G., Pitt, S., Doweyko, A. M., Sack, J. S., Mathur, A., McKinnon, M., Barrish, J. C., Dodd, J. H., Schieven, G. L., & Leftheris, K. (2007). Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds. Bioorganic and Medicinal Chemistry Letters, 17(18), 5019-5024. https://doi.org/10.1016/j.bmcl.2007.07.029

@article{810d6dd2c6d94e3ebdf77e59da22193c,

title = "Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds",

abstract = "The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.",

author = "\{Murali Dhar\}, \{T. G.\} and Wrobleski, \{Stephen T.\} and Shuqun Lin and Furch, \{Joseph A.\} and Nirschl, \{David S.\} and Yi Fan and Gordon Todderud and Sidney Pitt and Doweyko, \{Arthur M.\} and Sack, \{John S.\} and Arvind Mathur and Murray McKinnon and Barrish, \{Joel C.\} and Dodd, \{John H.\} and Schieven, \{Gary L.\} and Katerina Leftheris",

year = "2007",

month = sep,

day = "15",

doi = "10.1016/j.bmcl.2007.07.029",

language = "English (US)",

volume = "17",

pages = "5019--5024",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "18",

}

Murali Dhar, TG, Wrobleski, ST, Lin, S, Furch, JA, Nirschl, DS, Fan, Y, Todderud, G, Pitt, S, Doweyko, AM, Sack, JS, Mathur, A, McKinnon, M, Barrish, JC, Dodd, JH, Schieven, GL & Leftheris, K 2007, 'Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 18, pp. 5019-5024. https://doi.org/10.1016/j.bmcl.2007.07.029

TY - JOUR

T1 - Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

AU - Murali Dhar, T. G.

AU - Wrobleski, Stephen T.

AU - Lin, Shuqun

AU - Furch, Joseph A.

AU - Nirschl, David S.

AU - Fan, Yi

AU - Todderud, Gordon

AU - Pitt, Sidney

AU - Doweyko, Arthur M.

AU - Sack, John S.

AU - Mathur, Arvind

AU - McKinnon, Murray

AU - Barrish, Joel C.

AU - Dodd, John H.

AU - Schieven, Gary L.

AU - Leftheris, Katerina

PY - 2007/9/15

Y1 - 2007/9/15

N2 - The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.

AB - The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.

UR - https://www.scopus.com/pages/publications/34547921999

UR - https://www.scopus.com/pages/publications/34547921999#tab=citedBy

U2 - 10.1016/j.bmcl.2007.07.029

DO - 10.1016/j.bmcl.2007.07.029

M3 - Article

C2 - 17664068

AN - SCOPUS:34547921999

SN - 0960-894X

VL - 17

SP - 5019

EP - 5024

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this