Structure-activity relationship studies of CNS agents, Part 31: Analogs of MP 3022 with a different number of nitrogen atoms in the heteroaromatic fragment--new 5-HT1A receptor ligands

Arch Pharm (Weinheim). 1996 Oct;329(10):451-6. doi: 10.1002/ardp.19963291006.

Abstract

Two series of new MP 3022 analogs, i.e. 1-(o-methoxyphenyl)-4-n-propylpiperazines (3, 4a, 4b, 6-9, and 12-13) and 2-(n-propyl)-1,2,3,4-tetrahydroisoquinolines (5a, 5b, 11a, and 11b) containing a terminal heteroaromatic system with a different number of nitrogen atoms, were synthesized and their 5-HT1A/5-HT2A and alpha 1 receptor affinity was assayed. The majority of investigated piperazines may be classified as non-selective 5-HT1A/5-HT2A/alpha 1 receptor ligands. Compounds 3, 4a, 4b, 7-9a with the highest affinity for 5-HT1A receptors (Ki = 4-54 nM) were tested in vivo. Their functional activity was differentiated; while 3, 8, and 9a behaved like weak antagonists of postsynaptic 5-HT1A receptors, 4b and 7 may be classified as potential partial 5-HT1A receptors, agonists. Isomer 4a has characteristic features of a potential weak postsynaptic 5-HT1A receptor agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / metabolism
  • Isoquinolines / pharmacology*
  • Ligands
  • Male
  • Nitrogen / chemistry*
  • Piperazines / chemical synthesis*
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / pharmacology

Substances

  • Isoquinolines
  • Ligands
  • Piperazines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Triazoles
  • 4-(3-(benzotriazol-1-yl)propyl)-1-(2-methoxyphenyl)piperazine
  • Nitrogen