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

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

Journal of medicinal chemistry (2009-09-24)
Nicola M Aston, Paul Bamborough, Jacqueline B Buckton, Christopher D Edwards, Duncan S Holmes, Katherine L Jones, Vipulkumar K Patel, Penny A Smee, Donald O Somers, Giovanni Vitulli, Ann L Walker
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Prednisolone, ≥99%
Supelco
Prednisolone, VETRANAL®, analytical standard
Sigma-Aldrich
Losmapimod, ≥98% (HPLC)