Synthesis and 5-HT3 affinity of new 3-substituted indoles at central nervous system

Drug Des Discov. 1996 Oct;14(2):157-70.

Abstract

A series of 3-imino and 3-aminomethyl-N-methylindoles, in which the amine substituents were 3-quinuclidyl and 1-adamantyl groups, were synthesized and their in vitro affinity towards 5-HT3 central receptors evaluated. Of the nine compounds tested, three caused displacement of 3H-BRL 43694 binding to 5-HT3. 2-Chloro-3-(3-quinuclidylimino)-1-methylindole, 4, was the most potent compound with an IC50 = 5.15 10(-8) M. Moreover, the monoamine oxidase inhibition activity was tested and three compounds were shown to be MAO inhibitors, their IC50 was in the range of that of (-)-Deprenyl. Again, 4 was the most potent compound. Structure-activity relationships within the series are briefly discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / metabolism
  • Female
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Male
  • Mice
  • Molecular Structure
  • Monoamine Oxidase Inhibitors / pharmacology
  • Quinuclidines / chemical synthesis*
  • Quinuclidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3

Substances

  • 2-chloro-3-(3-quinuclidylimino)-1-methylindole
  • Indoles
  • Monoamine Oxidase Inhibitors
  • Quinuclidines
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3