Enzyme inhibitors XXIII: Syntheses of 9‐(substituted aralkyl)‐6‐substituted purines as inhibitors of adenosine deaminase

A series of 9‐(substituted aralkyl)‐6‐substituted purines was prepared as potential inhibitors of adenosine deaminase. The adenine derivatives were reversible inhibitors of adenosine deaminase, with potencies not strikingly different than the corresponding benzyl derivatives. However, 9‐(p‐bromoacetamidophenethyl)‐adenine (XV) and 9‐(3‐o‐ and p‐bromoacetamidophenylpropyl)‐adenines (XXIXa and XXIXb) were incapable of causing irreversible inhibition of adenosine deaminase, whereas the corresponding ortho‐ and para‐benzyl derivatives (I and II) and 9‐(m‐bromoacetamidophenethyl)adenine (IV) caused rapid irreversible inactivation of this enzyme. These experiments demonstrated the selectivity of irreversible inhibition that can be obtained by site‐directed irreversible enzyme inhibitors.