Studies on Ca2+ channel antagonists. 5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylpentyl isothiocyanate, a chemoaffinity ligand derived from verapamil

J Med Chem. 1986 Sep;29(9):1789-92. doi: 10.1021/jm00159a040.

Abstract

Reduction of 1 (verapamil) afforded amine 2, which was converted with thiophosgene to isothiocyanate 3, a chemoaffinity ligand for Ca2+ channels. Compound 3 showed concentration-dependent negative inotropic effects in rat right myocardial ventricular strips, EC50 = (4.56 +/- 3.40) X 10(-6) M (mean +/- SD), being slightly less potent than 4 (gallopamil), EC50 = (1.95 +/- 1.22) X 10(-6) M. It displaced [3H]gallopamil in rat myocardial membranes, IC50 = (3.42 +/- 2.51) X 10(-7) M, approximately equipotent with 1. It showed irreversible antagonism of [3H]gallopamil binding when preincubated at 10(-5) M; only 25% of [3H]gallopamil binding vs. control was observed. This agent may be a useful chemoaffinity ligand to aid in characterization of Ca2+ channels.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Affinity Labels
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Chemical Phenomena
  • Chemistry
  • Depression, Chemical
  • Gallopamil / metabolism
  • Ion Channels / metabolism
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism
  • Rats
  • Verapamil / analogs & derivatives*
  • Verapamil / chemical synthesis
  • Verapamil / metabolism
  • Verapamil / pharmacology

Substances

  • Affinity Labels
  • Calcium Channel Blockers
  • Ion Channels
  • 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentyl isothiocyanate
  • Gallopamil
  • Verapamil
  • Calcium