Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1115-8. doi: 10.1016/s0960-894x(03)00026-x.

Abstract

We searched for non-nucleoside inhibitors of adenosine deaminase by rational structure-based de novo design and succeeded in the discovery of 1-(1-hydroxy-4-phenyl-2-butyl)imidazole-4-carboxamide (FR221647: K(i)=5.9 microM to human ADA) as a novel inhibitor with moderate activity and good pharmacokinetics compared with the known inhibitors pentostatin and EHNA.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenosine Deaminase Inhibitors*
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Injections, Intraperitoneal
  • Mice
  • Models, Molecular
  • Pentostatin / pharmacology
  • Structure-Activity Relationship

Substances

  • Adenosine Deaminase Inhibitors
  • Enzyme Inhibitors
  • Pentostatin
  • 9-(2-hydroxy-3-nonyl)adenine
  • Adenine