6-苯基-4,5-二氢-3(2H)-哒嗪酮合成方法改进

从芳醛、吗啉及氰化钾制得的α-取代苯基吗啉乙腈(2),与丙烯腈1,4-加成,可合成3-芳酰丙酸(5)。5与肼反应可得6-取代苯基-4,5-二氢-3(2H)-哒嗪酮(1)。

3-取代哌嗪-6-取代苯基哒嗪的合成及抗惊活性的研究

由芳香醛与吗啡啉、氰化钾反应形成的α-芳基-α-(4-吗啉)乙腈,可对α、β不饱和腈或酯进行1,4-加成,生成1,4-酮酸型化合物。此物与肼缩合,再经芳构化即得6-劳基-3(2H)哒嗪酮。后者再经氯化及氨解可得3-氨基-6-芳基哒嗪。本文应用此法合成了15个3-取代哌嗪-6-取代苯基哒嗪类化合物,并初步测定了它们的抗惊(MES)活性。

6-芳基-3-(4-取代哌嗪)哒嗪类化合物的合成及抗惊厥活性

由芳香醛与吗啉、氰化钾反应形成的α-芳基-α-(4-吗啉)乙腈,可对α、β-不饱和腈或酯进行1,4-加成,生成1,4-酮酸型化合物。此物与肼缩合,再经芳构化即得6-芳基-3-哒嗪酮。后者再经氯化及氨解可得3-氨基-6-芳基哒嗪。应用此法合成了10个3-取代哌嗪-6-取代苯基哒嗪类化合物,并初步测验了它们的抗惊厥(MES)活性。

A Sensitive HPLC-MS/MS Analysis of Dencichine in Rat Plasma and Its Application to Pharmacokinetics

In order to quantitate dencichine in biological samples, a selective and sensitive method for the determination of dencichine in rat plasma based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated. (l)-2-amino-3-(carboxymethylthio)propionic acid was used as the internal standard (I.S.). After a protein precipitation extraction with acetonitrile, dencichine and the I.S. were chromatographed on an Xterra MS-C18 column. The mobile phase was consisted of 20mmol/L ammonium acetate solution-acetonitrile (35:65, V/V) at a flow rate of 0.2 mL/min. The detection was performed on a triple quadrupole mass via electrospray ionization (ESI) source in the positive mode. The intra- and inter-day precision (relative standard deviation, R.S.D.) values of dencichine were below 6.7%. The extraction recoveries were up 85%. The lower limit of quantification was 20 ng/ml, which was sensitive enough to detect the analyte. The HPLC-MS/MS method was successfully applied to the pharmacokinetic study after an intravenous administration of dencichine in Sprague-Dawley (SD) rat.

2-(3-羧甲基-4-苯硫基苯基)丙酸的制备

2-(3-羧甲基-4-苯硫基苯基)丙酸(1)是消炎镇痛药扎托洛芬(zaltoprofen)的关键中间体[1]。文献以5-丙酰基-2-苯硫基苯乙酸甲酯(2)为原料,在碘和氧化亚铜复合催化下,与原甲酸三甲酯经碘代缩酮、重排、水解一锅反应制得1,总收率为72%[1],方法中碘成本较高,不宜在工业上采用。