STUDIES ON DRUGS FOR CORONARY DISEASES Ⅱ. SYNTHESIS OF COMPOUNDS RELATED TO CHANGROLIN AS POTENTIAL ANTIARRHYTHMIC DRUGS

During clinical trials, Changrolin (Ⅰ) was found to show therapeutic effect in relieving ventricular premature beats, auricular premature beats and paroxysmal ventricular tachycardia. However, this agent still has some side effects to be overcome.A series of analogs and related compounds of the following types were synthesized: Ⅱ, Ⅲ, Ⅳ were synthesized by condensation of the correspounding chloro quinazoline, quinolin, or naphthalene with 4-aminophenol and then subjected to Mannich reaction. Similarly, Compound V was prepared from N-substituted p-aminophenol by reacting with formaldehyde and various amines. Ⅵ was prepared by reacting 4-chloroquinazline with the corresponding amine under different conditions.Pharmacological results showed that compounds 1, 5, 7, 8, 14, 15, 17 exhibited protective effects against experimental arrhythmias induced by aconitine. Compound 14 was perhaps more effective than Changrolin in protecting dogs from the atrial fibrillation induced by topical application of acetylcholine. Further studies on chemical modification of changrolin arc still in process.