Synthesis and biological evaluation of tetramisole analogs as inhibitors of alkaline phosphatase of the 6-thiopurine-resistant tumor sarcoma 180/TG
- 1 September 1979
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 22 (9) , 1030-1033
- https://doi.org/10.1021/jm00195a003
Abstract
Tetramisole and its analogs are potent inhibitors of alkaline phosphatase, including isoenzymes of mouse 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 inhibitory 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-tetrahydro-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 thiazole ring system of the tetramisole structure is apparently required for maximum inhibitory potency of this series against alkaline phosphatase.This publication has 1 reference indexed in Scilit:
- Tetramisole analogs as inhibitors of alkaline phosphatase, an enzyme involved in the resistance of neoplastic cells to 6-thiopurinesJournal of Medicinal Chemistry, 1977