Design and synthesis of novel p38α MAP kinase inhibitors: discovery of pyrazole-benzyl ureas bearing 2-molpholinopyrimidine moiety.

The discovery that pyrazole-benzyl urea derivatives bearing a 2-molpholinopyrimidine moiety are novel p38α inhibitors is described. A comparative view of the binding modes of SB-203580 and BIRB-796 by structural alignment of two X-ray co-crystal structures was utilized to identify this novel series. Modification of the benzyl group led to compound 2b, a highly potent p38α inhibitor.

Catalytic Leuckart-Wallach-type reductive amination of ketones.

A CpRh(III) complex catalyzes reductive amination of ketones using HCOONH(4) at 50-70 degrees C to give the corresponding primary amines in high yields. The reaction is clean and operationally simple and proceeds at a lower temperature and with higher chemoselectivity than the original Leuckart-Wallach reaction. The new method has been applied to the synthesis of alpha-amino acids directly from alpha-keto acids.