Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers

Bioorg Med Chem Lett. 2007 Jan 15;17(2):476-81. doi: 10.1016/j.bmcl.2006.10.042. Epub 2006 Oct 21.

Abstract

A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 microM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology*
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Cell Line
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Indicators and Reagents
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Membrane Potentials / drug effects
  • Mibefradil / pharmacology
  • Models, Molecular
  • Patch-Clamp Techniques

Substances

  • 1,3-dioxoisoindoline-5-carboxamide
  • Amides
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Indicators and Reagents
  • Indoles
  • Mibefradil