1—（2，6—二甲基苯氧基）—2—（3，4—二甲氧基苯乙氨基）丙烷盐酸盐的药理作用

1 - ( 2 ,6—二甲基苯氧基 )— 2— ( 3,4—二甲氧基苯乙氨基 )丙烷盐酸盐 [1 - ( 2 ,6-ｄｉｍｅｔｈｙｌｐｈｅｎｏｘｙ ) - 2 - ( 3,4-ｄｉｍｅｔｈｏｘｙｐｈｅｎｙｌｅｔｈｙｌａｍｉｎｏ)ｐｒｏｐａｎｅｈｙｄｒｏｃｈｌｏｒｉｄｅ ,ＤＤＰＨ ,简称Ｄ]是根据抗心律失常药“美西律”的结构特点 ,由我国专家自行设计合成的新化合物。主要作用是降血压。降压机理研究表明 :Ｄ具有α1 受体的阻断作用和较弱的α2 受体阻断作用及抗钙作用[1 ,2 ] 。1　除压作用Ｄ 3、 1 0ｍｇ·ｋｇ- 1 ｉｖ降低麻醉 ,清醒正常血压大鼠和肾型高血压大鼠的血…     

1—（3—和4—氟—2，6—二甲基苯氧基）丙酮的合成

目的 合成1－（3－和4－氟－2,6－二甲基苯氧基）丙酮（Ⅱa）和1－（4－氟－2,6－二甲基苯氧基）丙酮(Ⅱb)。方法 两化合物均以2,6－二甲基苯酚（Ⅷ）为超始原料,经硝化、还原、Schiemann反应、缩合制得,但在合成这两个目标化合物时,所采用的硝化试剂、保护基团、去保护基团顺序及氟化条件均有所不同。结果 合成出（Ⅱa）、（Ⅱb）及3－氟－2,6－二甲基苯酚（Ⅴa）,未见文献报告,经波 数据及元素分析确证其结构。结论 新合成的两个氟化合物Ⅱa和Ⅱb将作为合成DDPH苯环氟取代物的中间体。     

THE EFFECTS OF DEPRENYL AND 1-METHYL-4-PHENYL-1, 2, 3, 6-TETRAHYDROPYRIDINE (MPTP) ON 2-DEOXYGLUCOSE UPTAKE IN THE MOUSE BRAIN

~3H-2-deoxyglucose (2-DG) autoradiographic technique was used to study the ef feets of a monoamine-oxidase-B (MAO-B) inhibitor deprenyl and the neurotoxin Ⅰ-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on 2-DG uptake in the mouse brain. Following MPTP intoxication, 2-DG uptake was increased in the substantia nigra and lo(?)us ceruleus. At the same time, obvious abnormal behavior of the animals was induced. In the mice pretreated with deprenyl, 2-DG uptake was similar to that of control animal. Ab normal behavior. though present, was significantly milder than in mice given MPTP alone. It is concluded that MPTP interferes with the glucose metabolism in the substantia nigra and locus ceruleus and induces remarkable abnormal behavioral syndrome of mice. These deleterious effects can be blocked by pretreatment with deprenyl.     

1—（1H—1，2，4—三唑基）—2—（2‘,4’—二氟苯基）—3—含硫侧链—2—丙醇类化合物的合成及其抗真菌活性

目的：研究不同含硫侧链的引入对三唑醇类化合物抗真菌活性的影响。方法：设计合成了15个含硫侧链取代三唑醇类化合物,其中13个为新化合物;选择了8种真菌为实验菌株,进行体外抑菌活性测试。结果：目标化合物对所选菌株均有一定的抑制活性,其中化合物2对白色念珠菌的MIC80值为2ug/ml,与氟康唑的活性相当;化合物7和10对白色念珠菌的MIC780值为0.5和0.25ug/ml ,分别为氟康唑活性的4倍和8倍。结论：适当的脂水分配系数对该类化合物体外抑菌活性的影响可能大于立体化学因素的影响。     

吡啶—2，6（1H，3H）二酮生物碱对兔血小板聚集和TXB2，6—Keto—PGF1α产生的

目的 研究吡啶-2,6（1H,3H）二酮生物碱（SH1）对二磷酸腺苷（ADP）,花生四烯酸（AA）和胶原（COL）诱导兔血小板聚集和TXB2和6-keto-PGF1α生成的影响。方法 用比浊法和放射免疫法。结果 SH10.8-3.0mmol.L^-1能显著地抑制2.0umol.L^-1ADP,33.3umol.L^-1AA和20.0g.L^-1COL诱导的兔血小板聚集并有良好的量效关系,SH13.0mmol.L^-1抑制TXB2产生,而增加6-keto-PGF1α产生,并因素6-keto-PGF1α和TXB2的比值增加。结论 SH1显著抑制血小板聚集和TXB2产生,同时增加6-keto-PGF1α产生。     

2，5—二（邻—经基苯基）—1，3，4—恶二唑的微波合成新方法

目的：建立一种2，5—二(邻—羟基苯基)—1，3，4—恶二唑的新的合成方法。方法：在微波条件下，以多聚磷酸作为脱水环合剂，用水杨酸和水合肼在敞开容器中，一步简便合成2，5—二(邻—羟基苯基)—1，3，4—恶二唑。结果：在微波功率为500W、间歇辐射的条件下，顺利发生闭环反应仅需不足2min时间(文献列为8h)，并以57．5％的产率生成2，5—二(邻—羟基苯基)—1，3，4-恶二唑。结论：与其他合成方法比较，本方法具有快速、节能的特点。     

用（3as，6aR）-1，3-联苄基-四氢-4H-噻嗯酮[3，4-d]咪唑-2，4（1H）-狄奥合成生物素

自Goldberg＆Sternbach首次合成d-生物素后，在图1中，哪一种是所需结构，多年来已经在技术上得到很好证明。与其它已公开发表的合成方法进行比较后，其主要优势在于立体专一性。一方面当原材料和相应的2羧酸依丁迪咪唑被拆分后，通过对反丁烯二酸的选择，     

1，4-二苯基-6-苯基氨基-1，3，5-三嗪-2（1H）-硫酮的合成与晶体结构

目的研究1,4-二苯基-6-苯基氨基-1,3,5-三嗪-2（1H）-硫酮（分子式C2,H16N4S,相对分子质量356．44）的合成方法和其单晶结构。方法先将一定量的苄脒、氢氧化钠和N,N-二甲基甲酰胺（DMF）混合放入10ml反应器中搅拌10min,然后将一定量的苯基异硫氰酸酯加入反应器中,预搅拌20S后,在110℃温度下微波辐射（MWI）15min,高产率得到目标化合物。化合物的结构通过核磁共振氢谱（^1HNMR）、红外光谱（IR）和高分辨率气相色谱质谱（HRMS）验证,并通过X—ray单晶衍射进一步确定了产物的结构。结果合成的标题化合物C21H16N4S结构通过单晶X射线衍射分析确定,单斜晶系,空间群C2／c,a=22．94（2）,b=9．5092（15）,c=22．027（2）A,d=90°,D=110．473（2）°,^γ=90°,R=0．0465andwR：0．0758。分子中新形成的1,3,5-三嗪-2（1H）-硫酮环是个平面结构;它与相邻的苯环接近于共平面,二者的二面角为7．36（0．17）;而它与相邻的N一取代苯环近似于垂直,二者的二面角为85．31（0．13）。结论提供了一种1,3,5-三嗪衍生物的绿色合成方法,并经过单晶衍生确定了其分子结构及分子结构中各个六员环之间的关系。     

MADOPAR-INDUCED DYSKINESIA IN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) HEMIPARKINSONIAN MONKEY MODEL

Infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right common carotid artery produced hemiparkinsonian syndrome on contralateral limbs in 5 rhesus monkeys. The hemiparkinsonian syndrome produced responded to madopar medication and the circling motion changed from toward the MPTP-treated side to away from the MPTP-treated side. Long term use of madopar developed a peak-dose dyskinesia of the face and limbs at the contralateral side. The toxic effect of MPTP was confirmed biochemically by reduction of nigrostriatal DA and histologically by degeneration of nigral neurons on the MPTP-treated side. It is concluded that this hemiparkinsonian monkey model will be of value in the elucidation of the neural mechanism underlying L-DOPA or DA agonists induced dyskinesia in Parkinson's disease and in the search for newer methods of treatment which would produce less dyskinesia.     

Eldepryl prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral neuronal apoptosis in mice

Objective To study the apoptotic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydrop yridine (MPTP) on the nigral dopaminergic neurons of mice and 1-methyl-4-phen ylpyridium ion (MPP(＋)) on pheochromocytoma (PC12) cells, as well as the antagon ism of Eldepryl against MPTP’s apoptotic effect.Methods Three groups of C(57)BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyn eucleotidyl transferase-mediated dUTP-x nick end labeling) and FACS (fluoresce nce activated cell sorting) analyses of neuronal apoptosis in the substantia nig ra. The same tests were employed in cell culture to examine apoptosis in PC12 c ells treated with MPP(＋), MPTP or PBS. Results Intraperitoneal administration of MPTP 30 mg/kg could induce nigral apoptos is, and oral use of Eldepryl prior to MPTP treatment could completely prevent the ni gral apoptosis caused by MPTP. MPP(＋), an intermediate metabolite of MPTP, coul d lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells. Conclusions The experiment indicated that the neurotoxin, MPTP, might cause the death of nig ral neurons through a mechanism of apoptosis and this effect might be mediated b y its bioactive intermediate metabolite MPP(＋). Eldepryl could protect the neurotoxicity from MPTP.