Synthesis and biological evaluation of a series of benzoxazole/benzothiazole-containing 2,3-dihydrobenzo[b][1,4]dioxine derivatives as potential antidepressants

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1766-70. doi: 10.1016/j.bmcl.2014.02.031. Epub 2014 Feb 20.

Abstract

A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a-5d and 8a-8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT1A and 5-HT2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension test (TST). The results indicated that the compounds exhibited high affinities for the 5-HT1A and 5-HT2A receptors and showed a marked antidepressant-like activity. Compound 8g exhibited high affinities for the 5-HT1A (Ki=17 nM) and 5-HT2A (Ki=0.71 nM) receptors; it also produced a decrease of the immobility time and exhibited potent antidepressant-like effects in the FST and TST in mice.

Keywords: 2,3-Dihydrobenzo[b][1,4]dioxine; 5-HT(1A); 5-HT(2A); Antidepressant; Benzoxazole/benzothiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / chemical synthesis
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Benzothiazoles / chemistry*
  • Benzoxazoles / chemistry*
  • Dioxins / chemical synthesis
  • Dioxins / chemistry
  • Dioxins / pharmacology*
  • Dose-Response Relationship, Drug
  • Hindlimb Suspension
  • Mice
  • Molecular Structure
  • Rats
  • Receptor, Serotonin, 5-HT1A / chemistry
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT2A / chemistry
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Structure-Activity Relationship
  • Swimming*

Substances

  • 2,3-dihydrobenzo(1,4)dioxin
  • Antidepressive Agents
  • Benzothiazoles
  • Benzoxazoles
  • Dioxins
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT1A