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

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.