New imide 5-HT1A receptor ligands - modification of terminal fragment geometry

Molecules. 2004 Feb 28;9(3):170-7. doi: 10.3390/90300170.

Abstract

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moieties derived from NAN190, were synthesized and evaluated in vitro for their ability to bind to the serotonin 5-HT(1A) and 5-HT(2A) receptors. All new derivatives from series a demonstrated high 5-HT(1A) affinities, whereas THIQ analogues were much less active. With respect to 5-HT(2A) receptors, three MPP derivatives presented moderate activity but the rest of the investigated compounds were practically inactive. The influence of changes in terminus geometry on 5-HT(1A) receptor affinity was analyzed in regard to model compounds NAN190and MM199.

MeSH terms

  • Animals
  • Buspirone / analogs & derivatives
  • Buspirone / chemistry
  • Humans
  • Ligands
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists*
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines / chemical synthesis
  • Tetrahydroisoquinolines / chemistry*
  • Tetrahydroisoquinolines / pharmacology

Substances

  • 8-(4-(2-(1,2,3,4-tetrahydroisoquinolinyl))butyl)-8-azaspiro(4.5)decane-7,9-dione
  • Ligands
  • Piperazines
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Tetrahydroisoquinolines
  • 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
  • 1-(2-methoxyphenyl)piperazine
  • Buspirone