Selenium-sulfur analogues. 1. Synthesis and biochemical evaluation of selenotetramisole.

(+/-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]selenazole (1-selenotetramisole) was prepared from 2-aminoselenazoline in a three-step synthetic sequence. Resolution with d-10-camphorsulfonic acid yielded the optical isomers which were compared with (+)- and (-)-tetramisole as inhibitors of alkaline phosphatase isoenzymes. At 8.7 X 10(-5) M the (-) isomer of both tetramisole and 1-selenotetramisole produced significant inhibition of bovine liver and placental isoenzymes but not of calf intestinal or human placental isoenzymes. The (+) isomers demonstrated no inhibition at these concentrations. The similarity in inhibitory activity of the (-) isomers indicates the virtual interchangeability of selenium for sulfur in the thiazolidine ring of the parent drug and the likelihood that 75Se-radiolabeled selenotetramisole can provide an in vivo tracer to tetramisole biodistribution.