Synthesis and biological evaluation of tetramisole analogues as inhibitors of alkaline phosphatase of the 6-thiopurine-resistant tumor sarcoma 180/TG.
Basic Information
ID: ALA3244162
Journal: J Med Chem
Title: Synthesis and biological evaluation of tetramisole analogues as inhibitors of alkaline phosphatase of the 6-thiopurine-resistant tumor sarcoma 180/TG.
Authors: Li C, Lee MH, Sartorelli AC.
Abstract: Tetramisole and its analogues are potent inhibitors of alkaline phosphatase, including isoenzymes of Sarcoma 180/TG which appear to be involved in the mechanism of resistance of this neoplastic cell line to the 6-thiopurines. To determine the requirement for the thiazole ring system of tetramisole for inhibitor potency, 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole, 2,3-dihydro-6-phenylimidazo[2,1-b]oxazole, and 2,3,5,6-phenylimidazo[2,1-a]imidazole were synthesized and tested for inhibitory activity against alkaline phosphatase isolated from Sarcoma 180/TG. The results indicate that 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole caused 50% inhibition at 0.21 mM, while the other synthesized compounds were inactive at a concentration of 1 mM; in contrast, tetramisole required only 0.045 mM for 50% inhibition of alkaline phosphatase activity. The findings support the concept that the thiazole ring system of the tetramisole structure is required for maximum inhibitory potency of this series against alkaline phosphatase.
CiteXplore: 490546
DOI: 10.1021/jm00195a003
Patent ID: ┄