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Bioorg Med Chem Lett. 2001 Nov 5;11(21):2867-70.

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

Author information

1
Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, PO Box 1539, King of Prussia, PA 19406, USA. jerry_1_adams@gsk.com

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.

PMID:
11597418
DOI:
10.1016/s0960-894x(01)00570-4
[Indexed for MEDLINE]

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