Design and synthesis of piperazine-indole p38α MAP kinase inhibitors with improved pharmacokinetic profiles

Derivatives of the 4-fluorobenzyl dimethylpiperazine-indole class of p38α MAP kinase inhibitors are described. Biological evaluation of these compounds focused on maintaining activity while improving pharmacokinetic (PK) properties. Improved properties were observed for structures bearing substitutions on the benzylic methylene.

SAR studies of the p38α MAP kinase inhibitor SCIO-469 focused on maintaining activity while improving pharmacokinetic properties. Advantages were noted for compounds bearing substituents on the benzylic methylene carbon.Figure optionsDownload as PowerPoint slide