5-Chloropyrazine-2-carboxylic acid was synthesized from 2-acetyl furan successively by oxidation with selenium dioxide, cyclization with glycinamide,chlorination with phosphorus oxychloride and oxidation with potassium permanganate. Influence factors such as the reaction temperature,time and the ratio of glycinamide and sodium hydroxide of cyclization were investigated and opti-mized by orthogonal experiment. The result showed that when the reaction time,the temperature and ratio were 3 h,10℃ and 1∶2. 5,the yield was increased by 23. 1%. Ethyl acetate acidized by hydrochloric acid was used as extractant in the final step in place of cation exchange column and the yield of 74. 8%was the same as the literature,but the cost was lower.

Objective:To design and synthesize 1,2,3,4-tetrahydroisoquinolines and to determine its inhibition effect on monoamine oxidase(MAO).Methods:1-aminomethyl-1,2,3,4-tetrahydroisoquinoline was synthesized from phenylethylamine via acylation,amination with phthalimide potassium,bisehler-napieralski cyclization,hydrazinolysis and reduction reaction.Then the title compounds were synthesized.Results:Four compounds with tetrahydroisoquinoline moiety were synthesized and their structures were confirmed by infrared spectroscopy,nuclear magnetic resonance spectroscopy and mass spectrometry.Pharmacological test in vitro showed that all the five compounds had certain MAO inhibitory activity,and compound(5~7) displayed preferable selective inhibition on MAO-A.Conclusion:The obtained compounds(5~7) need further study.

Objective:To construct a screening model for monoamine oxidase(MAO) inhibitors in the treatment of neurodegenerative diseases.Methods:Benzylamine and 5-hydroxytryptamine(5-HT) were used as MAO-B and reaction substrates and their activities were measured by UV spectrophotometry,respectively.MAO concentration,substrate concentration,phosphate buffer concentration and pH,reaction time and temperature were optimized.Results:The optimized reaction system conditions were obtained as follows:under the conditions of enzyme pre-incubation time of 20 min and reaction time of 60 min at the temperature of 37 ℃,optimum condition for determination of MAO-B activity was 100 mmol/L phosphate buffer(pH 7.6) and 0.15 mg/ml MAO and 2.00 mmol/L benzylamine,optimum condition for determination of MAO-A activity was 100 mmol/L phosphate buffer(pH 7.4) and 0.40 mg/ml MAO and 5.00 mmol/L 5-HT.Conclusions:A screening model for monoamine oxidase inhibitors in vitro is constructed successfully.Due to its low cost and simple operation,it is suitable for large-scale screening MAO-B and MAO-A inhibitors.

Objective:To investigate the inhibition of rasagiline on monoamine oxidase(MAO) in mouse liver and brain tissues.Methods:After being extracted by differential centrifugation,activities of MAO-A and MAO-B in mouse liver and brain tissues were determined by UV spectrophotometry respectively.Results:Inhibition effect of rasagiline was stronger on MAO-B than on MAO-A and inhibition effect of rasagiline was stronger in the brain than in the liver.Conclusion:Rasagiline exerts selective inhibition effects on MAO-B in mouse liver and brain tissues.

Objective:To design a method for synthesizing 1,2,3,4-tetrahydro-1-naphthalenamine hydrochloride,which is an important intermediate for monoamine oxidase(MAO) inhibitors.Methods:1,2,3,4-tetrahydro-1-naphthylamine hydrochloride(11) was synthesized from benzene via acylation,reduction,cyclization,condensation,reduction,and salification by methods of Fridel Crafts acylation,Wolf-kishner-HUANG Minglong reduction and Harwoth cyclization.Results:Overall yield for synthesizing 1,2,3,4-tetrahydro-1-naphthylamine hydrochloride(11) was 43.6%.Conclusions:Method for synthesizing 1,2,3,4-tetrahydro-1-naphthalenamine hydrochloride is establish.Optimized synthetic route has advantages in industrial production for its cheap and readily available raw materials,easy in operation,high yield and high quality of products.