Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity.
Article Details
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Adams JL, Boehm JC, Gallagher TF, Kassis S, Webb EF, Hall R, Sorenson M, Garigipati R, Griswold DE, Lee JC
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.
- PubMed ID
- 11597418 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) SB220025 Mitogen-activated protein kinase 14 IC 50 (nM) 20 N/A N/A Details SB220025 Mitogen-activated protein kinase 14 IC 50 (nM) 19 N/A N/A Details