Synthesis and pharmacological evaluation of novel tricyclic[2,1-f]theophylline derivatives

Arch Pharm (Weinheim). 2013 Nov;346(11):832-9. doi: 10.1002/ardp.201300257. Epub 2013 Oct 1.

Abstract

The multireceptor strategy was implemented to obtain potential antipsychotics and/or antidepressants in a series of long-chain arylpiperazines bearing a tricyclic theophylline fragment. Their binding profile toward monoaminergic receptors (α1, 5-HT(1A), 5-HT(2A), 5-HT6, 5-HT7, D2, D3) was determined as well. The selected compounds 7 and 9 were tested in functional in vivo models and showed, like atypical antipsychotic drugs, presynaptic 5-HT(1A) receptor agonistic and postsynaptic 5-HT(1A), 5-HT(2A), and D2 receptor antagonistic activity.

Keywords: Depression; Imidazo[2,1-f]purine-2,4-diones; Long-chain arylpiperazines; Schizophrenia; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / chemical synthesis*
  • Antidepressive Agents, Tricyclic / metabolism
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Body Temperature Regulation / drug effects
  • Dopamine D2 Receptor Antagonists / chemical synthesis
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Male
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Rats, Wistar
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Agonists / chemical synthesis
  • Serotonin 5-HT1 Receptor Agonists / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists / chemical synthesis
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Structure-Activity Relationship
  • Theophylline / analogs & derivatives
  • Theophylline / chemical synthesis*
  • Theophylline / metabolism
  • Theophylline / pharmacology*

Substances

  • Antidepressive Agents, Tricyclic
  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Theophylline