Design and synthesis of a novel L-dopa-entacapone codrug

J Med Chem. 2002 Mar 14;45(6):1379-82. doi: 10.1021/jm010980d.

Abstract

A novel codrug, in which L-Dopa and entacapone are linked via a biodegradable carbamate spacer to form a single chemical entity, was synthesized and studied kinetically. This carbamate codrug provides adequate stability [t(1/2) = 12.1 h (pH 1.2); 1.4 h (pH 5.0); 1.1 h (pH 7.4)] against chemical hydrolysis but rapidly hydrolyzes to L-Dopa and entacapone in liver homogenate (t(1/2) = 7 min; pH 7.4) at 37 degrees C. The therapeutical potential of this novel codrug is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / chemical synthesis
  • Antiparkinson Agents / chemistry*
  • Carbamates / chemical synthesis
  • Carbamates / chemistry
  • Catechols / chemistry*
  • Half-Life
  • Humans
  • Kinetics
  • Levodopa / chemistry*
  • Nitriles
  • Rabbits

Substances

  • Antiparkinson Agents
  • Carbamates
  • Catechols
  • Nitriles
  • Levodopa
  • entacapone