Synthesis of 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, a new class of dopamine agonists

J Med Chem. 1984 Dec;27(12):1607-13. doi: 10.1021/jm00378a014.

Abstract

A series of tricyclic oxazines, namely, the 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, have been synthesized and assayed for dopamine agonist activity. One of the members of this series, compound (+)VII-15, was found to be a remarkably potent agonist in vivo when tested in the standard 6-hydroxydopamine lesioned rat assay. The absolute configuration of the compound corresponds to that found in the active isomer of apomorphine. Its activity at the alpha 2 receptor (vs. [3H]clonidine) is relatively low. It also failed to stimulate the synthesis of cAMP in the carp retina assay, thus giving the compound a highly selective profile in favor of the D2 receptor.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apomorphine / metabolism
  • Cattle
  • Cerebral Cortex / metabolism
  • Clonidine / metabolism
  • Dopamine / analogs & derivatives*
  • Hydroxydopamines / pharmacology
  • Indicators and Reagents
  • Models, Molecular
  • Molecular Conformation
  • Motor Activity / drug effects
  • Oxazines / chemical synthesis*
  • Oxazines / pharmacology
  • Oxidopamine
  • Rats
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Rotation
  • Structure-Activity Relationship

Substances

  • Hydroxydopamines
  • Indicators and Reagents
  • Oxazines
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine
  • Oxidopamine
  • Clonidine
  • Apomorphine
  • Dopamine