抗心律失常药物的研究Ⅲ──1－对硝基（或氨基）苯基－3－正丁胺基－1，2－丙二醇的合成  

Studies on Antiarrhythmic Agents Ⅲ Synthesis of p-Substituted 1-Phenyl-3-Butylamino-1, 2-Propanediol

作　　者：王如斌[1] 彭司勋[1] 华维一[1] 

机构地区：[1]山东医科大学药物化学教研室,中国药科大学药物化学研究室

出　　处：《中国药物化学杂志》1995年第2期140-142,149,共4页Chinese Journal of Medicinal Chemistry

摘　　要：设计合成了两个取代苯丙二醇胺类化合物，均未见文献报道，其化学结构经红外光谱、核磁共振、质谱和元素分析确证，用氯仿诱发小鼠心律失常的模型进行试验表明。对氨基苯丙二醇丁胺具有显著的抗心律失常活性。p-NO2-(Ⅰ)and p-NH2-C6H4CH(OH)CH(OH)CH2NHCH2(CH2)2CH3(Ⅱ)were prepared.Screening tests of both compounds indicated that(Ⅱ)could markedly antagonize CHCl3-induced arrhythmia in mice.Thus,p-NO2-C6H4CHO was treated with MeOH-KOH and AcH,and the resulting p-NO2-C6H4CH=CHCHO was reduced to p-NO2-C6H4CH= CHCH2OH with(iso-Pro)3 Al.Treatment of p-NO2-C6H4CH=CHCH2OH with SOCl2 gave 69% of p-NO2-C6H4CH=CHCH2Cl, which(3.8g)was refluxed with 20mL CH3(CH2)2CH2NH2 10 h to give 91% of p-NO2-C6H4CH=CHCH2NH(CH2)3CH3. Acetylation of it gave quant. p-NO2-C6H4CH=CHCH2N(Ac) (CH2)3CH3, which(4.8g)in acetone was oxidized with 3. 85 g of KMnO4-2. 9 g MgSO4 to give 30. 5% of p-NO2-C6H4CH(OH)CH(OH)CH2NHCH2(CH2)2CH3. Hydrolysis of it with 10% aq. NaOH in EtOH gave 45% of(Ⅰ). Reduction of(Ⅰ)with Fe and HCl gave 84. 5% of(Ⅱ),which could antagonize 71.4% of CHCl3-induced arrhythmias in mice.

关 键 词：抗心律失常药 苯丙二醇胺 合成 药理 

分 类 号：R972.2[医药卫生—药品] TQ463.26[医药卫生—药学]