Synthesis and pharmacology of the enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin

J Med Chem. 1990 Oct;33(10):2925-9. doi: 10.1021/jm00172a038.

Abstract

The enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin (3) have been synthesized and evaluated for activity at central dopamine (DA), 5-hydroxytryptamine, and norepinephrine (NE) receptors, by use of biochemical and behavioral tests in rats. In addition, the affinities of the compounds for striatal [3H]spiroperidol and [3H]N-propylnorapomorphine binding sites were determined. The absolute configuration of the enantiomers was determined by X-ray diffraction of (+)-3. The pharmacological effects of both enantiomers are complicated, but (2R,3S)-7-hydroxy-3-methyl-2-(dipropylamino)tetralin [(-)-3] produced biochemical effects in vivo similar to those elicited by classical DA D2-receptor antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin* / analogs & derivatives*
  • Animals
  • Apomorphine / analogs & derivatives
  • Apomorphine / metabolism
  • Binding, Competitive
  • Cattle
  • Chemical Phenomena
  • Chemistry, Physical
  • Computer Simulation
  • Crystallography
  • Dihydroxyphenylalanine / metabolism
  • Dopamine Antagonists*
  • In Vitro Techniques
  • Isomerism
  • Male
  • Molecular Conformation
  • Molecular Structure
  • Motor Activity / drug effects
  • Rats
  • Reserpine / pharmacology
  • Spiperone / metabolism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes*
  • X-Ray Diffraction

Substances

  • Dopamine Antagonists
  • Tetrahydronaphthalenes
  • 8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin
  • Spiperone
  • N-n-propylnorapomorphine
  • Dihydroxyphenylalanine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Reserpine
  • 5-Hydroxytryptophan
  • Apomorphine