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.
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-beta-D-ribofuranosyl)-v-triazolo[4,5-d]pyridazine- 4 (5H)-thione and 1-(2,3,5-tri-O-acetyl-beta-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-(beta-D-ribofuranosyl)imidazo[4,5-d]pyrida zine and 4-(p-nitrobenzylthio)-1-(beta-D-ribofuranosyl)-v-triazolo[4,5-d]py ridazine, 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.
Bussolari
J C
JC
Department of Medicinal Chemistry, University of Rhode Island, Kingston 02881, USA.
Stoeckler
J D
JD
Panzica
R P
RP
D000345:Affinity Labels / Q000737:chemistry*; D001692:Biological Transport / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D009705:Nucleosides / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000737:chemistry; D013872:Thionucleosides / Q000737:chemistry*
D000345:Affinity Labels; D009705:Nucleosides; D013872:Thionucleosides; D013868:Thioinosine; C065224:nitrobenzylthioformycin; C001789:4-nitrobenzylthioinosine