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.