Studies on Ca2+ channel antagonists. 5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2- isopropylpentyl isothiocyanate, a chemoaffinity ligand derived from verapamil.
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.
D000345:Affinity Labels; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003864:Depression, Chemical; D005711:Gallopamil / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D014700:Verapamil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D000345:Affinity Labels; D002121:Calcium Channel Blockers; D007473:Ion Channels; C050047:5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentyl isothiocyanate; D005711:Gallopamil; D014700:Verapamil; D002118:Calcium