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Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors

dc.contributor.authorDas, Jagabandhu
dc.contributor.authorMoquin, Robert V.
dc.contributor.authorPitt, Sidney
dc.contributor.authorZhang, Rosemary F.
dc.contributor.authorShen, Ding Ren
dc.contributor.authorMcIntyre, Kim W.
dc.contributor.authorGillooly, Kathleen M.
dc.contributor.authorDoweyko, Arthur M.
dc.contributor.authorSack, John S.
dc.contributor.authorZhang, Hongjian
dc.contributor.authorKiefer, Susan E.
dc.contributor.authorKish, Kevin
dc.contributor.authorMcKinnon, Murray
dc.contributor.authorBarrish, Joel C.
dc.contributor.authorDodd, John H.
dc.contributor.authorSchieven, Gary L.
dc.contributor.authorLeftheris, Katerina
dc.date2022-08-11T08:08:51.000
dc.date.accessioned2022-08-23T16:10:22Z
dc.date.available2022-08-23T16:10:22Z
dc.date.issued2008-03-25
dc.date.submitted2009-02-23
dc.identifier.citationBioorg Med Chem Lett. 2008 Apr 15;18(8):2652-7. Epub 2008 Mar 10. <a href="http://dx.doi.org/10.1016/j.bmcl.2008.03.019">Link to article on publisher's site</a>
dc.identifier.issn1464-3405 (Electronic)
dc.identifier.doi10.1016/j.bmcl.2008.03.019
dc.identifier.pmid18359226
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32917
dc.description.abstractThe synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2x was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18359226&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.bmcl.2008.03.019
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titlePyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors
dc.typeJournal Article
dc.source.journaltitleBioorganic and medicinal chemistry letters
dc.source.volume18
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1469
dc.identifier.contextkey733766
html.description.abstract<p>The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2x was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed.</p>
dc.identifier.submissionpathgsbs_sp/1469
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages2652-7


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