SYNTHESIS OF HEGINAMINE DERIVATIVES AND THEIR OPEN-RING ANALOGUES

In an attempt to improve the clinical efficacy and enhance the stability of heginamine (Ⅰ), a series of its derivatives and their open-ring analogues were synthesized. The ring-substituted phenethyl amines were reacted with acids or diacids to give corresponding amides (2～3) and bis-amides (6～10), which were transformed into products (A_1～2,E_1～4)by reduction, β-(3,4-methelene dioxy)-phenethyl amine was allowed to react with β-chloropropionyl and morpholine to produce amino-amide (5). B₁ and D_1～2 were formed by cyclization and reduction from (5) and (9, 10) respectively. (5) was reduced directily to produce (C₁). In animal test compound D₂ was shown to have significant activity and was superior to heginamine.