Synthesis and biochemical properties of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine.
The synthesis and characterization of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine (3a) are presented. This compound is a substrate for adenosine deaminase and adenosine kinase. In L1210 cells 3a is converted to 8-aminoinosine monophosphate (4b), apparently by the action of AMP deaminase on the monophosphate of 3a, as well as to the triphosphate derivative of 3a. Pentostatin was used to inhibit adenosine deaminase, and coformycin was used to inhibit AMP deaminase in experiments designed to delineate the metabolic fate of 3a. Pentostatin was without influence on the cytotoxicity of 3a, but coformycin potentiated the cytotoxicity. The potentiation was associated with an increased cellular concentration of phosphates of 3a and a decreased concentration of 4b.
D000659:AMP Deaminase / Q000037:antagonists & inhibitors; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D007291:Inosine Monophosphate / Q000378:metabolism; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism; D015649:Pentostatin; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D011684:Purine Nucleosides; D003070:Coformycin; D007291:Inosine Monophosphate; D015649:Pentostatin; C050335:8-amino-6-fluoro-9-ribofuranosyl-9H-purine; D000659:AMP Deaminase