Enzyme Inhibitors. VIII. Studies on the Mode of Binding of Some 6-Substituted 9-(Hydroxyalkyl)purines to Adenosine Deaminase

The syntheses of some 6-substituted 9-02-hydroxypropyl)puriiies mid some 6-subslit uted 9-(2,3-dihydroxypropyl)purines have been accomplished by the condensation of f>amino-4,6-dichloropyrimidine with the appropriate amino alcohols, followed by ring closure of the resultant substituted pyrimidines to give the desired 6-chloro-It-substituted purines. Displacement of the ti-chloro group by certain nucleophilic reagents gave a variety of 6-substituted derivatives. Enzymatic evalualion of these compounds established that the 6-amino and the 6-methylamino derivatives inhibited adenosine deaminase. Comparison of the 6-aminopurines which were substituted at the 9-position by n-propyl, 3-hydroxypropyl, 2-hydroxypropyl, and 2,3-dihydroxypropyl groups established that there is only one hydroxyl binding site on adenosine deaminase in the. area two to three carbons removed from the 9-position of the purine nucleus.