2. Academic Validation
  3. Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity

Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity

  • Bioorg Med Chem Lett. 2001 Nov 5;11(21):2867-70. doi: 10.1016/s0960-894x(01)00570-4.
J L Adams 1,  J C Boehm,  T F Gallagher,  S Kassis,  E F Webb,  R Hall,  M Sorenson,  R Garigipati,  D E Griswold,  J C Lee
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, PO Box 1539, King of Prussia, PA 19406, USA. jerry_1_adams@gsk.com
PMID: 11597418 DOI: 10.1016/s0960-894x(01)00570-4
Abstract

Optimization of a series of N-1-cycloalkyl-4-aryl-5-(pyrimidin-4-yl)imidazole inhibitors of p38 kinase is reported. Oral administration of inhibitors possessing a cyclohexan-4-ol or piperidin-4-yl group at N-1 in combination with alkoxy, amino(alkyl), phenoxy and anilino substitution at the 2-position of the pyrimidine was found to potently inhibit LPS-induced TNF in mice and rats. The selectivity of these new inhibitors for p38 kinase versus eight Other protein kinases is high and in all cases exceeds that of SB 203580.

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