Detail of "39593-08-3"

Reference

Synthesis, cardiac electrophysiology, and b-blocking activity of novel arylpiperazines with potential as class II/III antiarrhythmic agents

Synthesis, cardiac electrophysiology, and b-blocking activity of novel arylpiperazines with potential as class II/III antiarrhythmic agents. Phillips, Gary B.; Morgan, Thomas K., Jr.; Lumma, William C., Jr.; Gomez, Robert P.; Lind, Joan M.; Lis, Randall; Argentieri, Thomas; Sullivan, Mark E. (Dep. Med. Chem.Some commonly used reagents like 39593-08-3 and 138286-71-2 are used in this experiment., Berlex Lab., Inc., Cedar Knolls, NJ 07927, USA). J. Med. Chem., 35(4), 743-50 (English) 1992. CODEN: JMCMAR. ISSN: 0022-2623. DOCUMENT TYPE: Journal CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 1 Cyclocondensation reaction of N-aryl-N'-(phenylmethyl)-1,2-ethanediamine with 2,3-dibromopropionamide followed by derivatization gave a series of novel arylpiperazines, e.g., I. Thus, the key step in the prepn. of the new compds. involves a regioselective heterocyclic ring formation. These were prepd. in an attempt to incorporate both class II (b-receptor blocking) and class III antiarrhythmic properties in a single mol. All but four compds. significantly prolonged action potential duration in canine cardiac Purkinje fibers (class III activity). All but one of the compds. demonstrated b-receptor affinity in a competitive binding assay and three had b1-receptor selectivity. Compared to sotalol, a ref. class II/III agent, I demonstrated b1-selectivity and was 1 order of magnitude more potent in the in vitro class III and the b1-receptor screens. I was evaluated further and found to be effective in preventing programmed elec. stimulation-induced arrhythmias in conscious dogs (class III activity) and against epinephrine-induced arrhythmias in halothane anesthetized dogs (class II activity). .