STUDIES ON DRUGS FOR CORONARY HEART DISEASE (Ⅰ) SYNTHESIS OF RING COMPOUNDS WITH SUBSTITUTED AMINO-ACETYL-AMINO GROUP

Angina pectoris is a clinical syndrome caused by transient myocardial ischemia which is due to an imbalance between myocardial oxygen supply and demand. Many drugs for the treatment of angina pectoris have been shown to increase myocardial tolerance of hypoxia, so it is of theoretical significance and practical value to search for compounds for improving the myocardial tolerance of hypoxia. In view of the fact that vitamin B₁₅ can improve the tolerance of hypoxia and Lidocaine possesses antiarrythmic activity, a series of ring compounds carrying substituted amino acetylamino groups were synthesized by combining these two structures in one molecule. These compounds were synthesized by condensation of suitable aniline or alcohol with chloroacetylchloride, followed by reacting with corresponding amines. Preliminary pharmacological examination revealed that some of the compounds especially ω-isopropylamino-2,4-dimethylacetanilide (15), the hydrochloride of ω-isopropylamino acetanilide (19) as well as the hydrocbloride of ω-diethylamino-3,4-dichloro-acetanilide (11) showed significant activity to improve the tolerance of hypoxia for heart, while, 4,6-Bis (isopropyl-amino acetylamino) 1,3-xylol (61), 4,6-Bis-(s-butylamino acetylamino) 1,3-xylol (62), 4,6-Bis (diisopropylaminoacetyl-amino) 1,3-xylol (60) did not exhibit such activity but possessed a strong antiarrythmic action.