Extremely potent orally active benzo[g]quinoline analogue of the dopaminergic prodrug: 1-propyl-trans-2,3,4,4a,5,7,8,9,10,10a-decahydro-1H-benzo-[g]quinolin-6-one [corrected]

J Med Chem. 2006 Feb 23;49(4):1494-8. doi: 10.1021/jm051111h.

Abstract

Enone prodrugs of dopaminergic catecholamines represent a new type of prodrug in the research area of dopamine agonists. Here, we demonstrate the first benzo[g]quinoline-derived enone that induces potent dopamine agonist effects similar to aminotetralin-derived enones. Significant effects of (-)-4 were observed in microdialysis studies after administration of 1 nmol kg(-1) sc and 3 nmol kg(-1) po. With a potency comparable to that of the most potent apomorphines, (-)-4 could potentially compete with L-DOPA and apomorphine in the treatment of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Naphthylamine / analogs & derivatives*
  • 2-Naphthylamine / chemistry
  • Administration, Oral
  • Animals
  • Corpus Striatum / metabolism
  • Crystallography, X-Ray
  • Dopamine Agonists / chemical synthesis*
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / pharmacology
  • In Vitro Techniques
  • Microdialysis
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 1-propyl-2,3,4,4a,5,7,8,9,10,10a-decahydro-1H-benzo(g)quinolin-6-one
  • Dopamine Agonists
  • PD 148903
  • Prodrugs
  • Quinolines
  • Quinolones
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • 2-Naphthylamine