(S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1- carbaldehyde: a new class of orally active 5-HT1A-receptor agonists

J Med Chem. 1993 Jul 23;36(15):2059-65. doi: 10.1021/jm00067a002.

Abstract

The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects
  • Biological Availability
  • Indoles / chemical synthesis*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / pharmacokinetics
  • Serotonin Receptor Agonists / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Indoles
  • Serotonin Receptor Agonists
  • 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz(e)indole-1-carbaldehyde
  • 8-Hydroxy-2-(di-n-propylamino)tetralin