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1. Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis.

Author

Andrews, Martin J.I., Andrew Clase, J., Bar, Gregory, Tricarico, Giovanni, Edwards, Paul J., Brys, Reginald, Chambers, Mark, Schmidt, Wolfgang, MacLeod, Angus, Hirst, Kim, Allen, Vivienne, Birault, Veronique, Le, Joelle, Harris, John, Self, Andrew, Nash, Kevin, and Dixon, Graham

Subjects
*RHEUMATOID arthritis treatment, *METALLOPROTEINASE regulation, *STRUCTURE-activity relationship in pharmacology, *PYRAZINES, *KINASES, *ENZYME inhibitors, *TARGETED drug delivery, *PHARMACOKINETICS, *THERAPEUTICS
Abstract

Abstract: MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds. [Copyright &y& Elsevier]

Published
2012
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