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J Med Chem. 2009 Oct 22;52(20):6257-69. doi: 10.1021/jm9004779.

p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression.

Author information

1
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Rd, Stevenage, Hertfordshire SG1 2NY, UK.

Abstract

p38alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFalpha and IL-1beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38alpha/beta inhibitors using crystal structures of our inhibitors bound to p38alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development.

PMID:
19772287
DOI:
10.1021/jm9004779
[Indexed for MEDLINE]

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