3-芳基-1,2,3,4-噁三唑-5-亚胺与阿司匹林偶联物的合成和抗血栓活性研究

取代苯胺经重氮化、还原得苯肼盐酸盐, 与硫氰酸钾作用得苯基取代的氨基硫脲, 再在亚硝酸异戊酯、盐酸的作用下环合、成盐, 加碱中和后生成3-芳基-1,2,3,4-噁三唑-5-亚胺, 最后与乙酰水杨酰氯反应得目标物6a～6l, 其结构经MS, IR, ¹H NMR和元素分析确证. 体外血小板聚集试验和小鼠肺血栓生成试验结果表明, 部分目标物在体内、外均显示出较好的抗血栓活性, 值得深入进行研究.     

生物合理设计光系统Ⅱ抑制剂研究 (Ⅶ)──2-氰基-3-甲硫基-3-芳氨基丙烯酸乙酯的合成及其Hil反应抑制活性

合成了化合物2-氰基-3-甲硫基-3-芳氨基丙烯酸乙酯(2a_2w),产物结构通过¹HNMR和元素分析证实,测定了所有化合物的Hil反应抑制活性.生物活性测定结果表明,部分化合物均表现出良好的抑制活性,初步分析了标题化合物结构与活性间的关系.     

含肉桂酰胺类化合物的合成及α-糖苷酶抑制活性

合成了4个未见报道的含肉桂酰胺类化合物9a～9b, 初步评价了它们的α-糖苷酶抑制活性. 这些化合物均具有α-糖苷酶抑制活性, 是一类结构新颖的α-糖苷酶抑制活性化合物, 其中, 化合物9b和9c的活性高于阳性对照药物阿卡波糖.     

β-D-葡萄糖基硫脲合成及生物活性研究

从1-溴-2,3,4,6-四乙酰化-β-D-吡喃葡萄糖I出发, 经异硫氰酸酯化反应, 合成了2,3,4,6-四乙酰化-β-D-吡喃糖基硫脲化合物IV, 再经脱乙酰化得到V. 将乙酰化糖基异硫氰酸酯的合成从文献的60%提高到80%. 所得化合物经元素分析, IR, MS, ¹H NMR和 ¹³C NMR谱学分析确定了结构, 并对产物进行了初步的除草活性测试.     

酰基硫脲化合物的合成及其生理活性

通过酰基异硫氰酸酯与胺类化合物的加成反应，合成了１５种酰基硫脉类化合物，化合物的结构经元素分析、ＩＲ、￣１ＨＮＭＲ等确证，初步生理活性实验表明，化合物２＿ｊ，２＿１对玉米种子的萌发和幼苗叶中的呼吸速率、叶绿素含量有显著促进效应。     

Synthesis of racemic 1,2,3,4-tetrahydroisoquinolines and their resolution

1-Aniline-substituted 3,4-dihydroisoquinolines were obtained in various ways using the Bischler-Napieralski reaction. The effect of the protecting group at the aniline nitrogen atom on the course of the reaction has been studied and it was found that the N-phthalyl group was stable under the cyclization conditions. The dihydroisoquinolines were reduced to the racemic 1,2,3,4-tetrahydroisoquinolines which were resolved by crystallization of the diastereomeric tartrates. Two examples of 1,2,3,4-tetrahydroisoquinolines were obtained in optically pure form (>99%ee).Dedicated to Professor M. A. Yurovskaya on her jubilee.Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia. email: peteris@osi.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 348–361, March, 2000.     

Synthesis and stereochemistry of 1-acyl-2-alkyl-1,2,3,4-tetrahydroquinoline-3,4-epoxides

Summary Analogous to the recently described synthesis of Reissert epoxides the treatment of 1-acyl-2-alkyl-1,2-dihydroquinolines withm-chloroperoxybenzoic acid gave diasteromeric pure epoxides which are stable in crystalline state, but reactive in solution versus nucleophiles. Acting as useful intermediates to stereocontrolled functionalized 1,2,3,4-tetrahydroquinolines an X-ray analysis was performed to confirm the relative stereochemistry of the epoxides.

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Synthese und Stereochemie von 1-Acyl-2-alkyl-1,2,3,4-tetrahydrochinolin-3,4-epoxiden

Zusammenfassung Analog zu der kürzlich beschriebenen Synthese von Reissert-Epoxiden liefern 1-Acyl-2-alkyl-1,2-dihydrochinoline bei Behandlung mitm-Chlorperbenzoesäure diastereomerenreine Epoxide, die sich als Festsubstanzen außerordentlich stabil, in Lösung aber reaktiv gegenüber Nucleophilen erweisen. Da sie wertvolle Ausgangsverbindungen zu 1,2,3,4-substituierten Tetrahydrochinolinen mit definierter relativer Konfiguration darstellen, wurde die Stereochemie der Epoxide mittels Röntgenstrukturanalyse abgesichert.

     

氨基酸羟胺钒配合物的合成、表征及对PTP1B酶的抑制活性

合成了2种羟胺氧钒配合物--缬(亮)氨酸羟胺氧钒, 并通过元素分析、红外光谱、紫外光谱、热重分析及X射线单晶衍射对其结构进行了表征. 采用PTP1B酶筛选模型评价了它们及相关配合物的PTP1B酶抑制活性. 实验结果表明, 这2种配合物同属于三斜晶系, P1空间群, 中心钒原子与7个配位的氮氧原子形成扭曲的五角双锥构型, 进而通过氢键作用形成三维晶体结构. 这2种配合物对PTP1B酶都表现出抑制活性, 亮氨酸羟胺氧钒在浓度为20 μg/mL时对PTP1B酶的抑制率达到90.51%.     

N-(2-羧基-1,3,4-噻二唑-5-基)-N''-芳酰基硫脲与芳氧乙酰基硫脲的合成与生物活性

为了寻找高活性的杂环农药,用5-氨基-1,3,4-噻二唑-2-羧酸与芳酰基异硫氰酸酯及芳氧乙酰基异硫氰酸酯反应,合成出18种新的芳酰基硫脲与芳氧乙酰基硫脲,采用红外光谱、核磁共振氢谱和元素分析证明了其结构,初步的生物活性测定试验表明,部分目标化合物具有良好的植物生长调节活性,其中2c,2d,3b和3g具有良好的生长素活性.     

Synthesis and Antioxidant Activity of New Thiazole Analogues Possessing Urea,Thiourea, and Selenourea Functionality

A new series of urea, thiourea, and selenourea derivatives with thiazole moieties were synthesized by the nucleophilic addition reaction of (2-amino-4-(3-chlorophenyl)thiazol-5-yl)(2-chlorophenyl)methanone with various substituted isocyanates/ isothiocyanates/isoselenocynates in acetone having a catalytic amount of sodium hydroxide at room temperature with good yields. All the synthesized compounds were fully characterized by spectroscopic data and screened for their in vitro antioxidant activity using 1,1-diphenylpicrylhydrazyl (DPPH), nitric oxide (NO), and hydrogen peroxide (H₂O₂) radical scavenging methods. A preliminary study of the structure–activity relationship revealed that the compounds containing selenourea functionality along with halogen group have exhibited potent activity (IC₅₀ ≤ 0.0309 µmol/mL) compared to the standards (IC₅₀ ≤ 0.0814 µmol/mL). Thus the title compounds are a new class of potent antioxidant agents and worthy of further investigation.     

N-(2-羧基-1,3,4-噻二唑-5-基)-N'-芳酰基硫脲与芳氧乙酰基硫脲的合成与生物活性

为了寻找高活性的杂环农药, 用5-氨基-1,3,4-噻二唑-2-羧酸与芳酰基异硫氰酸酯及芳氧乙酰基异硫氰酸酯反应, 合成出18种新的芳酰基硫脲与芳氧乙酰基硫脲, 采用红外光谱、核磁共振氢谱和元素分析证明了其结构, 初步的生物活性测定试验表明, 部分目标化合物具有良好的植物生长调节活性, 其中2c, 2d, 3b和3g具有良好的生长素活性.     

The Synthesis of Some New Quinazolone Derivatives of Potential Biological Activity

The refluxing of 3-amino-6,8-dibromo-2-thioxo-2,3-dihydro-1H-quinazolin-4-one (5) with ethyl chloroformate and/or ethyl chloroacetate afforded compounds 6 and 7 . The reaction of 5 with ethyl bromobutyrate, chloroacetyl chloride, phenacyl chloride, and phenyl isocyanate yielded compounds 8 , 9 , 11 , and 12 . The coupling of 5 with (2,3,4,6-tetra-O-acetyl-α -D-gluopyranosyl)bromide( ABG ) in DMF at r.t. gave 3-amino-6,8-dibromo-2-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)thioxo-2,3-dihydro-1H-quinazolin-4-one ( 14 ). The deblocking of 14 in sodium methoxide gave 5 . 3-Amino-6,8-dibromo-2-methylthio-3H-quinazolin-4-one ( 16 ) was prepared by stirring 5 with methyl iodide in methanol. The treatment of 16 with hydrazine hydrate afforded 4 . The condensation of 4 with aldehydes furnished 3,5-dibromo-2-arylaminobenzoic acid hydrazide ( 18a–c ). The refluxing of 18a with acetic anhydride gave 3-(benzylideneamino)-6,8-dibromo-2-methyl-3H-quinazolin-4-one ( 19 ). Hydrazones 20a–f were prepared by the condensation of 4 with pentoses and/or hexoses. The acetylation of ( 20a–f ) with acetic anhydride gave the acetyl derivatives 21a–f .     

新型一枝蒿酮酸异噁唑衍生物的合成及其抗A,B型流感病毒活性研究

为了提高一枝蒿酮酸的生物活性,以一枝蒿酮酸和3-取代苯基-5-氨甲基-异噁唑为原料,在偶合试剂DCC,HOBt/DMAP的作用下,合成了6个未见文献报道的含异噁唑的一枝蒿酮酸酰胺衍生物3a～3f.所合成的化合物均经过IR,1H NMR,13C NMR,ESI-MS等分析方法表征及初步体外抗A(H3N2,H1N1)型和B型流感病毒活性研究.初步实验结果表明:化合物3c同时具有抗A(H3N2)型和B型流感病毒活性,化合物3c和3e表现出比母体化合物强的抗B型流感病毒活性.     

益母草碱类似物设计、合成及其Na+/H+交换器-1抑制活性

以中药益母草中有效成分益母草碱为先导化合物,按生物电子等排原理,设计合成了18个益母草碱类似物.通过MS,1H NMR,13C NMR对化合物结构进行表征.初步的药效研究结果表明部分化合物具有Na+/H+交换器-1 (NHE-1)抑制活性,其中化合物1a和1e的活性显著强于阳性对照药Cariporide.     

Design,Synthesis, and Thrombin Inhibitory Activity Evaluation of Some Novel Benzimidazole Derivatives

Some benzimidazole derivatives were designed and screened via molecular docking. Six compounds which obtained high scores were selected for synthesis and all compounds were characterized by ¹H‐ and ¹³C‐NMR, and HR‐ESI‐MS. Subsequently, these compounds were evaluated for their inhibitory activities on thrombin. Compound 5a (IC₅₀ 3.11 nm ) showed a better activity than the reference argatroban (IC₅₀ 9.88 nm ). These results, along with related molecular model studies, indicated that 5a could be a potential thrombin inhibitor for further research.     

2-氰基-3-甲硫基-3-苄氨基丙烯酸取代苯氧乙酯的合成及其除草活性

基于D1蛋白结构模型,设计并合成了一系列2-氰基-3-甲硫基-3-苄氨基丙烯酸取代苯氧乙酯,结构经¹HNMR、元素分析和IR确证.生物活性结果表明,化合物显示出较好的Hill反应抑制活性;而酯基部分的乙氧乙氧基被苯氧乙氧基取代后,活性有所下降,其原因可能是苯环分散了β-氧原子上的电荷密度,使之与Ser268的结合力降低,这进一步证实了Ser268位点的重要性.同时实验结果证明,苯环上的取代基对化合物活性有一定影响.     

中国毛虾流感病毒神经氨酸酶抑制活性肽的研究

以中国毛虾为原料, 以抑制流感病毒神经氨酸酶(NA)活性为初筛指标, 通过控制酶切位点制备了具有抑制NA活性的酶解液. 利用凝胶层析和高效液相色谱等技术分离纯化出高活性的抑制肽, 其IC₅₀ 值为96.1 μmol/L.经串联质谱测定该抑制肽序列为EISYIHAEAYRRGELK, 紫外光谱分析结果证明该抑制肽能与NA结合.基于反向对接, 应用SYBYL软件模拟抑制肽与NA活性区域结合, 确定了抑制肽与NA的结合位点. 细胞毒性实验测得该抑制肽对细胞的最大无毒浓度(TC₀)为1.26 mg/mL.在红细胞凝集实验中, 随着抑制肽浓度增大, 病毒的凝集价显著降低, 证明抑制肽的抗病毒作用具有多靶点.     

One Pot Synthesis of Some New Heteroylselenoglycolic Acids and Their Biological Activity

Abstract

A convenient one pot three-stage synthesis was used for obtaining new heteroylselenoglycolic and di-heteroylselenoglycolic acids by nucleophilic substitution reaction of the starting compounds pyridineselenol, pyridazineselenol, and quinolineselenol with α-chloro- or α,α-dichloroacetic acids for 1-h stirring. The newly synthesized compounds were screened biologically for anti-microbial and anti-oxidant activities. The structure of all new compounds was confirmed by ¹H NMR, ¹³C NMR, Mass, and IR spectroscopy and elemental analyses.