Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents:: parallel synthesis for lead optimization of amide region

A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides were identified by high throughput screening. Optimization of the amide region by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described. The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line. © 2005 Elsevier Ltd. All rights reserved.