Enzyme Inhibitors XVI

The syntheses of a variety of 6-substituted-9- (2-hydroxybutyl)-, 9- (2-hydroxyheptyl)-, and 9-(2-hydroxyoctyl)purines have been completed. Those compounds with a 6-amino or a 6-methylamino group were inhibitors of adenosine deaminase, the compounds with a 6-amino group being more active than those compounds with a 6-methylamino group. For a series of 9-substituted adenines, the decreasing order of binding was: 9- (2-hydroxypropyl)>9- (2-hydroxyethyl). ≅ 9- (2-hydroxybutyl) >9-(2-hydroxyheptyl)>9-(2-hydroxyoctyl). From the data, it is concluded that there is a specific binding site for the terminal methyl group in 9- (2-hydroxypropyl) adenine and that the hydroxyl binding site and the main hydrophobic site of adenosine deaminase cannot be bridged by adenine derivatives which are substituted at the 9-position by straight-chain alkyl group bearing a hydroxyl group on carbon 2.