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

Abstract

The synthesis of S 4-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.