Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione

Pol J Pharmacol. 2003 Jul-Aug;55(4):553-7.

Abstract

Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo-hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All tested compounds exhibited moderate to low 5-HT1A receptor affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki = 27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists. Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5-dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Binding, Competitive
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / metabolism*
  • Pyrrolidines / pharmacology
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin Agents / chemical synthesis
  • Serotonin Agents / metabolism*
  • Serotonin Agents / pharmacology
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / metabolism*
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • 3-spiro-beta-tetralonepyrrolidine-2,5-dione
  • 3-spiro-cyclo-hexanepyrrolidine-2,5-dione
  • Pyrrolidines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Agents
  • Spiro Compounds
  • Receptor, Serotonin, 5-HT1A