Synthesis and biological activities of some N6-(nitro- and -aminobenzyl)adenosines

Synthesis and biological activities of 12 analogs of N6-benzyladenosine are described. The compounds were prepared by two methods: (1) direct alkylation of adenosine with an appropriately substituted benzyl bromide to give the N1-substituted derivative which was then rearranged in base to give the N6-substituted compound, and (2) by nucleophilic displacement of chlorine in 6-chloropurine ribonucleoside, 6-chloro-2-aminopurine ribonucleoside, and 6-chloro-2-aminopurine with an amine. These analogs were examined for their growth inhibitory effect in cultured leukemic cells and also for their effect on adenosine aminohydrolase activity. N6-p-Nitrobenzyladenosine and its 2'-deoxy analog were competitive inhibitors (K1 65, 22 MUM). The 2-amino-N6-p-nitrobenzyladenine and its ribonucleoside were found to be noncompetitive inhibitors of adenosine aminohydrolase. In cultured L1210 leukemia, 2-amino-6-p-nitrobenzylaminopurine and the corresponding ribonucleoside were better growth inhibitors than N6-benzyladenosine, while N6-p-nitrobenzyladenosine, its 2'-deoxy analog, and N6-p-fluorobenzyladenosine were as active as N6-benzyladenosine.