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

Bioorg Med Chem Lett. 2001 Nov 19;11(22):2893-6. doi: 10.1016/s0960-894x(01)00591-1.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Deaminase Inhibitors*
  • Animals
  • Azepines / chemical synthesis*
  • Azepines / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Guanine Deaminase / antagonists & inhibitors*
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Liver / drug effects
  • Liver / enzymology
  • Rabbits

Substances

  • 4,6-diamino-8H-1-hydroxyethoxymethyl-8-iminoimidazo(4,5-e)(1,3)diazepine
  • Adenosine Deaminase Inhibitors
  • Azepines
  • Enzyme Inhibitors
  • Imidazoles
  • Guanine Deaminase