The synthesis and biological evaluation of 4-p-nitrobenzylthio-v-triazolo[4,5-d]pyridazine and imidazo[4,5-d]pyridazine ribosides as potential nucleoside transport inhibitors

Article abstract of DOI:10.1016/0968-0896(96)00188-5

The synthesis of S⁴-substituted nucleosides possessing the imidazo- and v-triazolo[4,5-d]pyridazine ring systems was undertaken and the compounds prepared were evaluated as inhibitors of nucleoside transport into human erythrocytes. 1-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-v- triazolo[4,5-d]pyridazine-4(5H)-thione and 1-(2,3,5-tri-O-acetyl-β-D- ribofuranosyl)imidazo[4,5-d]pyridazine-4(5H)-thione were each synthesized by two different routes and served as precursors for the title analogues. The nitrobenzylmercaptopurine riboside (NBMPR) analogues, 4- (p-nitrobenzylthio)-1-(β-D-ribofuranosyl)imidazo[4,5- d]pyridazine and 4-(p-nitrobenzylthio)-1-(β-D- ribofuranosyl)-v-triazolo[4,5-d]pyridazine, inhibited the transport of adenosine, but were approximately 4- and 28-fold less active, respectively than NBMPR and nitrobenzylthioformycin, known potent and specific inhibitors of carrier-mediated transport.