SAR of 2,6-diamino-3,5-difluoropyridinyl substituted heterocycles as novel p38MAP kinase inhibitors.

Bioorg Med Chem Lett 2002 Aug;12(16):2109-12

Arthritis and Bone Research, Novartis Pharma AG, CH-4002, Basel, Switzerland.

2,6-Diamino-3,5-difluoropyridinyl substituted pyridinylimidazoles, -pyrroles, -oxazoles, -thiazoles and -triazoles have been identified as novel p38alpha inhibitors. Pyridinylimidazole 11 potently inhibited LPS-induced TNFalpha in mice, showed good efficacy in the established rat adjuvant (ED(50): 10 mg/kg po b.i.d.) and collagen induced arthritis (ED(50): 5 mg/kg po b.i.d.) with disease modifying properties based on histological analysis of the joints.

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http://dx.doi.org/10.1016/s0960-894x(02)00336-0DOI Listing
August 2002

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