Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: Exploration of core and headpiece structure–activity relationships

A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece.

Graphical abstractA novel series of antiproliferative agents containing a pyrazolo[1,5-a]pyrimidine scaffold and the structure–activity relationship studies of the headpiece, core are described.Figure optionsDownload full-size imageDownload as PowerPoint slide