High-throughput synthesis and optimization of thrombin inhibitors via urazole α-addition and Michael addition

A novel α-addition of propiolates to urazoles followed by Michael addition of a variety of nucleophiles has been developed for rapid production and optimization of peptidomimetic drug leads. This technology has produced a number of highly potent and selective inhibitors of the serine protease, thrombin. [Copyright &y& Elsevier]