2′,4′-二氯苯基哒嗪衍生物的抗小鼠癫痫作用

本文对2′,4′-二氯苯基哒嗪衍生物对几种实验性癫痫模型的对抗作用进行了研究,其中化合物Ⅰ和Ⅱ对最大电休克发作实验(MEST),戊四唑(Met)印防己毒素发作和荷包牡丹碱发作等四种实验性癫痫模型均有很强的对抗作用,强于苯妥英钠,苯巴比妥和卡马西平,但也显示中枢抑制作用,预防指数不高,化合物Ⅲ和Ⅳ对这四种动物惊厥模型亦有较强的对抗作用,均大大强于丙戊酸钠和乙琥胺,其中化合物Ⅲ的中枢神经系统毒性较低,抗MEST的预防指数高达23.4.     

6-取代苯基-3(2H)哒嗪酮的合成、抗惊活性及其构效关系的研究

本文报道了14个6-取代苯基-4,5-二氢-3(2H)哒嗪酮和15个6-取代苯基-3(2H)哒嚎酮的合成及其抗电惊活性。其ED50值表明,以2′,4′-二氯苯基-3(2H)哒嗪酮的抗惊作用为最强。构效分析表明,苯环上的取代基对化合物的抗惊活性有明显影响,吸电子取代基和疏水性参数值较大的取代基有利于提高化合物的抗惊活性。     

6-取代苯基-3(2H)哒嗪酮的合成、抗惊活性及其构效关系的研究

本文报道了14个6-取代苯基-4,5-二氢-3(2H)哒嗪酮和15个6-取代苯基-3(2H)哒嚎酮的合成及其抗电惊活性。其ED₅₀值表明,以2′,4′-二氯苯基-3(2H)哒嗪酮的抗惊作用为最强。构效分析表明,苯环上的取代基对化合物的抗惊活性有明显影响,吸电子取代基和疏水性参数值较大的取代基有利于提高化合物的抗惊活性。     

6-取代苯基哒嗪的3位γ-氨基丁酸衍生物的合成及抗惊活性

GABA的合成类似物是开发新型抗惊剂和抗癫痫药物的新领域。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(2H)哒嗪酮。后者再经氯化后。与GABA缩合,制备3-(N-GABA)-6-芳基哒嗪类及其分子内脱水产物3-(N-丁内酰胺)-6-芳基哒嗪类化合物。本文应用此法合成了17个上述苯代哒嗪的GABA衍生物,并初步测验了它们的抗惊(MES)活性。活性最强的是3-(N-GABA)-6-(2′,4′-二氯苯基)哒嗪(ED₅₀=21.05mg/kg)。     

6-取代苯基哒嗪的3位γ-氨基丁酸衍生物的合成及抗惊活性

GABA的合成类似物是开发新型抗惊剂和抗癫痫药物的新领域。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(2H)哒嗪酮。后者再经氯化后。与GABA缩合,制备3-(N-GABA)-6-芳基哒嗪类及其分子内脱水产物3-(N-丁内酰胺)-6-芳基哒嗪类化合物。本文应用此法合成了17个上述苯代哒嗪的GABA衍生物,并初步测验了它们的抗惊(MES)活性。活性最强的是3-(N-GABA)-6-(2′,4′-二氯苯基)哒嗪(ED_(50)=21.05mg/kg)。     

血吸虫病化学治疗的研究 ⅩⅩⅩⅥ.4-苯基(或烯丙基)-5-(吡嗪-2)-1,2,4-三唑-3-硫酮衍生物的合成

本文报导28个4-苯基(或烯丙基)-5-(吡嗪-2)-1,2,4-三唑-3-硫酮衍生物的合成。这类化合物的合成是以吡嗪甲酸乙酯与水合肼反应得2-吡嗪甲酰肼,再与不同的异硫氰酸酯作用后,在2N氢氧化钠溶液中环合而得Ⅱ或Ⅲ,然后经烷化、酰化及Mannich反应,分别制得相应的化合物。其中Ⅲ_1和Ⅲ_2对感染日本血吸虫小白鼠有明显肝移作用。     

血吸虫病化学治疗的研究 ⅩⅩⅩⅥ.4-苯基(或烯丙基)-5-(吡嗪-2)-1,2,4-三唑-3-硫酮衍生物的合成

本文报导28个4-苯基(或烯丙基)-5-(吡嗪-2)-1,2,4-三唑-3-硫酮衍生物的合成。这类化合物的合成是以吡嗪甲酸乙酯与水合肼反应得2-吡嗪甲酰肼,再与不同的异硫氰酸酯作用后,在2N氢氧化钠溶液中环合而得Ⅱ或Ⅲ,然后经烷化、酰化及Mannich反应,分别制得相应的化合物。其中Ⅲ₁和Ⅲ₂对感染日本血吸虫小白鼠有明显肝移作用。     

6,7-亚甲二氧基-1(2H,4H)-吖啶酮衍生物的合成及镇痛作用

报道13个6,7-亚甲二氧基-1(2H,4H)-吖啶酮衍生物的合成。初步药理实验表明:合成的化合物均有不同程度的镇痛作用,其中化合物Ⅱe的镇痛效力最强。     

4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮的合成及抗惊厥作用研究

目的筛选抗惊厥活性的化合物,寻找新型抗癫痫药物。方法以肉桂酸为原料,对其化学结构进行优化,合成了4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮。采用最大电休克发作实验(MES)测定其抗癫痫活性。结果采用红外光谱、核磁共振氢谱和质谱确定了化学结构。经药理活性筛选发现4-(4-甲氧基苯基)-3,4-二氢-2(1H)-喹啉酮具有抗惊厥作用。结论本合成路线简单、产物易分离,为开发新的抗癫痫药物提供了新思路。     

血吸虫病化学治疗的研究——ⅩⅩⅩⅦ.β-(5-硝基-4-溴-2-呋喃)-及β-(4,5-二溴-2-呋喃)丙烯酰胺及其酯类的合成

本文报道β-(4,5-二溴-2-呋喃)-及β-(5-硝基-4-溴-2-呋喃)丙烯酰胺及其酯类衍生物26个的合成。动物筛选结果表明;化合物Ⅲ_(?)。,Ⅲ_6和Ⅲ_(13)对感染日本血吸虫小白鼠有明显的治疗作用。化合物Ⅱ_(?)有较明显的预防作用。     

2，6－哌嗪二酮类抗肿瘤药物的研究1－取代苯基－4－（2′，3′－二乙酰氧基－5′－甲氧羰基苄基）－2，6－哌嗪二酮的合成

本文设计合成了１１个１－取代苯基－４－（２′，３′－二乙酰氧基－５′－甲氧羰基苄基）－２，６－哌嗪二酮类化合物，并经对小鼠白血病细胞Ｐ３８８、小鼠肝癌细胞Ｈｅｐ和人体胃癌细胞ＳＧＣ７９０１的体外实验表明，化合物９ｊ对Ｐ３８８白血病细胞有较强的抑制作用，化合物９ｄ对Ｈｅｐ肝癌细胞有较强的抑制作用。本文还考察了超声波辐射时间对Ｍａｎｎｉｃｈ反应的影响。     

CYP3A in horse intestines

The intestinal enterocytes provide the initial site for cytochrome P450 (CYP)-mediated metabolism of orally absorbed xenobiotics. In man and some animal species, the CYP3A subfamily is highly expressed in the intestines and considered to be important in the first-pass metabolism of drugs and other xenobiotics. The aim of the present study was to investigate the mRNA expression, immunohistochemical localization and catalytic activity of CYP3A in the intestines of horse. Real-time RT-PCR analyses showed that the highest CYP3A mRNA expression was present in the duodenum with a decreasing level towards jejunum, ileum, cecum, and colon. The CYP3A mRNA expression in the liver was similar as in the anterior part of the jejunum, but about 4.5 times lower than in the anterior part of the duodenum. Immunohistochemistry showed CYP3A immunoreactivity in the cytoplasm of the enterocytes, which decreased distally along the intestinal tract. CYP3A-dependent metabolic activity rose slightly from the anterior to the distal part of the duodenum and the anterior part of the jejunum and then declined to the middle and distal parts of the jejunum and the ileum, cecum, and colon. Our results suggest that CYP3A in the small intestine plays a major role in first-pass metabolism and may affect bioavailability and therapeutic efficiency of some orally administrated drugs in horse.     

2-(4-氯-3-甲基苯基)-1,2,4-三嗪-3,5(2H,4H)-二酮的合成

对硝基邻甲苯胺经重氮化、氯代、还原、闭环、水解、脱羧6步反应得到2-（4-氯-3-甲基苯基）-1,2,4-三嗪-3,5（2H,4H）-二酮,总收率约40%。     

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)。     

Cyclo-oxygenase-1 inhibition increases acid secretion by modulating H+,K+-ATPase expression and activation in rabbit parietal cells

1. In the present study, we evaluated the role of cyclo-oxygenase (COX)-1 and COX-2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [(14)C]-aminopyrine uptake, prostaglandin (PG) E(2) synthesis and COX-1, COX-2 and proton pump expression at baseline and after treatment with various concentrations of specific COX-1 (SC-560), COX-2 (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methyl-sulphonyl)phenyl-2 (5H)-furanone; DFU) and non-specific COX (indomethacin) inhibitors. 2. In parietal cells, SC-560 and indomethacin, over the concentration range 10(-8) to 10(-4) mol/L, dose-dependently increased basal and 10(-4) mol/L histamine-stimulated aminopyrine uptake and inhibited PGE(2) synthesis, whereas DFU (10(-8) to 10(-5) mol/L) had no effect. However, at 10(-4) mol/L, DFU augmented histamine-stimulated aminopyrine uptake by 135% and inhibited PGE(2) synthesis by 39%, indicating an inhibition of COX-1 at this higher concentration. 3. The SC-560-, DFU- and indomethacin-induced augmentation of histamine-stimulated aminopyrine uptake was reduced to basal levels after 10(-5) mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10(-4) mol/L ranitidine only partially inhibited such augmentation. 4. Only COX-1 was detected in parietal cells. However, both COX-1 and COX-2 were expressed in gastric glands, with relative protein density of COX-1 being sixfold higher than that of COX-2. Protein levels of COX-1 in parietal cells and those of COX-1 and COX-2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine. 5. Parietal cell proton pump expression was significantly enhanced by 10(-5) mol/L SC-560 and 10(-4) mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10(-5) mol/L DFU had no effect. 6. In conclusion, the data indicate that inhibition of COX-1- but not COX-2-derived PGE(2) synthesis is involved in augmentation of non-steroidal anti-inflammatory drug-induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.     

马蓝的化学成分研究

Seven compounds have been isolated from the whole plant of Strobilanthes cusia (Nees) O. Ktze. Three of them are triterpenes (Ⅰ～Ⅲ), two are indole alkaloids (Ⅳ, Ⅴ), two are quinazolinone alkaloids (Ⅵ, Ⅶ). On the basis of spectral analysis and physicochemical properties, their structures were established as lupeol (Ⅰ), betulin (Ⅱ), lupenone (Ⅲ), indigo (Ⅳ), indirubin (Ⅴ), 4 (3H)-quinazolinone (Ⅵ), 2, 4 (1H, 3H)-quinazolinedione (Ⅶ). Ⅵ and Ⅶ were found from natural plant for the first time.The results of the pharmacological tests demonstrate that compound Ⅴ has anticancer activity and compound Ⅵ has hypotensive action. Compound Ⅶ can be quantitatively determined by HPLC, which may serve as a quality control standard for materia medica and its preparations. Compounds Ⅵ and Ⅶ have been confirmed by means of synthesis.     

6-甲基-4-(1H)-吡啶酮-3-羧酸的制备

目的制备 6 甲基 4 (1H) 吡啶酮 3 羧酸。方法以 4 羟基 6 甲基 2 吡喃酮、N ,N 二甲基甲酰胺二甲氧基缩醛为起始原料 ,经两步反应制得目标化合物。结果与结论经熔点测定及1H NMR、MS分析确证目标产物结构 ,总收率为 39 6 % ,高于文献收率