3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐的合成及其生物活性研究

α,β-不饱和环戊酮的Mannich碱和α,β-不饱和环己酮的Mannich碱具有显著的抗炎活性,为了寻求新的具有抗炎活性的环酮类化合物,设计了3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐作为目标化合物。以苯酚、γ-丁内酯、甲醛和哌啶等原料合成了目标化合物,并利用熔点、红外光谱、核磁共振氢谱等手段确定了其结构。采用二甲苯致小鼠耳肿胀法,测定了该化合物的抗炎活性,实验结果表明在200mg/kg剂量下该化合物对二甲苯所致小鼠耳肿胀的抑制率为54.5%。采用Born's比浊法测定了该化合物的抗血小板聚集活性,实验结果表明该化合物的抗血小板聚集活性比噻氯匹啶强约23倍。

Synthesis and Biological Activity of 3,4-Dihydro-4-(1-piperidinomethyl)-5H-benzoxepin-5-one

The mannich base dervatives of α,β-unsaturated cyclopentanone and cyclohexanone are known to exhibit anti-inflammatory activity. In order to find some new compounds with cyclic ketone moiety which be expected to exhibit anti-inflammatory activity,3,4-dihydro-4-(1-piperidinomethyl)-5H-benzoxepin-5-one was designed as the target compound. The target compound were synthesized from phenol, -butyrolactone,formaldehyde and piperidine as the starting raw materials,and characterized by melting point,infrared spectra and proton 1H NMR spectra. The anti-inflammatory activity was evaluated using xylene-induced mouse ear swelling model,and the inhibitory rate of 54.5% at the dose of 200 mg/kg. Using Born's method,the anti-platelet aggregative activity was evaluated,and the inhibitory activity was about 23 times more potent than that of ticlopidine.