Adenosine deaminase inhibitors.  Synthesis and biological activity of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine. 
Two new deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 1), 7-deaza-EHNA (6) and 1,3-dideaza-EHNA (11), were synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity and compared with EHNA, 1-deaza-EHNA (2), and 3-deaza-EHNA (3).  Substitution of a methine group for a nitrogen atom in the 7-position of the purine moiety of EHNA produces a dramatic drop in the inhibitory activity (Ki = 4 X 10(-4) M) whereas compounds 2 and 3 are still good inhibitors (Ki = 1.2 X 10(-7) M and 6.3 X 10(-9) M respectively).  EHNA and its deaza analogues so far synthesized were also tested in vitro for their antiviral and antitumor activity in a range of cellular systems.  EHNA and 1-deaza-EHNA are equiactive as inhibitors of human respiratory syncytial virus (HRSV) replication (MIC = 6.25 micrograms/mL) while the other compounds are inactive.  On the other hand, all the examined compounds displayed an antitumor activity comparable to that of the reference compound 1-beta-D-arabinofuranosyladenine (ara-A), 7-deaza-EHNA being the most active of all.  The results obtained showed that there is no correlation between adenosine deaminase inhibition and antiviral or antitumor activity in this series of compounds.  3-Deaza-EHNA, the most active inhibitor of ADA among the EHNA deaza analogues, greatly potentiates the antitumor activity of ara-A in vitro.  In vivo activity was observed only when the two compounds were used in combination.