A unique ring-expanded acyclic nucleoside analogue that inhibits both adenosine deaminase (ADA) and guanine deaminase (GDA; guanase): synthesis and enzyme inhibition studies of 4,6-diamino-8H-1-hydroxyethoxymethyl-8-iminoimidazo[4,5-e][1,3]diazepine.
The synthesis and enzyme inhibition studies of a novel ring-expanded acyclic nucleoside analogue are reported. Compound has been found to be a competitive inhibitor of both adenosine deaminase (ADA) and guanine deaminase (GDA; guanase) with K(i)'s equal to 1.52+/-0.34 x 10(-4) M and 2.97+/-0.25 x 10(-5) M, respectively. Inhibition of two enzymes of purine metabolism may bear beneficial implications in antiviral therapy.
Wang
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Laboratory for Drug Design and Synthesis, Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Hosmane
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RS
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011817:Rabbits
C443748:4,6-diamino-8H-1-hydroxyethoxymethyl-8-iminoimidazo(4,5-e)(1,3)diazepine; D058892:Adenosine Deaminase Inhibitors; D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D006148:Guanine Deaminase