Synthesis, determination of absolute configuration, and biological evaluation of spiro-fused thiadiazoline inhibitors of kinesin spindle protein (KSP)

A facile and highly convergent synthesis of biologically active spiro-fused thiadiazoline KSP inhibitors is reported. The highlights of the synthesis include the Michael reaction and cyclization of thiosemicarbazone to 1,3,4-thiadiazoline. This chemistry lends itself to the preparation of (+)-2, a potent and orally bioavailable anti-cancer agent, and to the development of a structure-activity relationship program.