A novel series of piperazinyl-pyridine ureas as antagonists of the purinergic P2Y12 receptor

A novel series of P2Y12 antagonists for development of drugs within the antiplatelet area is presented. The synthesis of the piperazinyl-pyridine urea derivatives and their structure–activity relationships (SAR) are described. Several compounds showed P2Y12 antagonistic activities in the sub-micromolar range.

A novel series of piperazinyl-pyridine ureas, exemplified by 1, was discovered to be P2Y12 antagonists. SAR investigations presented several compounds with potencies in the sub-micromolar range. The pyridine 3-ethoxycarbonyl substituent, the urea N–H of the linker, and the right-hand aromatic ring all contributed significantly to potency. Solubility could be increased by shifting from 2-CF3/5-CN to 2-H/5-Cl pyridines.Figure optionsDownload as PowerPoint slide