2-取代苯基-5-(3,4,5-三甲氧基苯基)-1,3,4-噁二唑衍生物的合成及生物活性研究

合成了10个2-取代苯基-5-(3,4,5-三甲氧基苯基)-1,3,4-噁二唑衍生物. 并经过元素分析, IR, ¹H NMR, ¹³C NMR对其结构进行了确认. 初步生物活性测试表明, 部分化合物具有一定抗癌活性.     

手性多噁唑啉的一步合成方法

尽管已报道了多种结构类型的手性单或双噁唑啉, 但手性多噁唑啉的合成及其应用的文献报道比较少. 本工作以多元羧酸为原料, 与手性2-氨基-1-丁醇经一步反应合成了8个手性多噁唑啉, 产率为89%～98%, 其结构经¹ H NMR谱、IR谱、MS谱和元素分析确证.     

含噁二唑杂环取代的新型三唑并嘧啶衍生物的合成及其生物活性

2-肼羰基亚甲硫基-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶与二硫化碳在乙醇溶液中回流制得化合物2-(5-巯基-1,3,4-噁二唑-2-亚甲硫基)-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶, 后者在碱性环境中与卤化苄反应得到17种新型双杂环化合物. 对所得化合物结构均经元素分析, ¹H NMR和MS确认. 初步生物活性测试表明这些化合物具有一定的杀菌活性.     

1,3,4-噁二唑衍生物的双光子吸收和双光子泵浦荧光

依据“推电子基-共轭中心-拉电子基-共轭中心-推电子基”的模型将电荷传输型1,3,4-噁二唑环嵌入芳香共轭体中, 通过Wittig-Horner反应合成了2种对称型强双光子吸收和双光子诱导荧光分子2,5-二[4-(2-芳基乙烯基)苯基]-1,3,4-噁二唑. 它们的氯仿溶液在锁模Nd: YAG激光器800 nm激光照射下, 发射出很强的双光子上转换荧光, 其最强荧光分别在波长507和475 nm. 采用非线性透过率法测得其双光子吸收截面分别为1.07×10^－46和6.6×10^－47 cm⁴•s•photon^－1. 这2个对称型D-π-A-π-D生色分子从激发端基到π共轭桥的有效能量传输, 对双光子吸收和双光子荧光发射能力贡献较大.     

3-(吗啉吡啶基)-5-取代异噁唑类化合物的合成及抗菌活性研究

以6-氯-3-吡啶甲醛为原料, 通过多步反应合成了一系列3-(吗啉吡啶基)-5-取代异噁唑类化合物, 并用IR, 1H NMR, 13C NMR和MS进行了结构确证. 这些化合物均以异噁唑为母核, 具有近似的平面结构, 在异噁唑环的3-位引入吗啉吡啶基, 而在5-位引入酯基、取代氨基、三唑环和噁唑烷酮环. 研究了这些化合物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和大肠杆菌的抑制活性, 发现与噁唑烷酮类上市药物利奈唑胺相比, 目标化合物均显示出更低的抗菌活性, 最低抑制浓度(MIC)大于32 mg/L, 这些试验结果表明异噁唑母核的5-位缺乏sp3杂化结构, 可能会导致抗菌活性的显著降低.     

含2-三氟甲基苯并咪唑的双噁二唑硫醚及其亚砜衍生物的合成

芳甲酰肼和氯乙酸在二甲苯中反应生成了一系列的2-芳基-5-氯甲基-1,3,4-噁二唑(1a～1j), 继而与2-(2-三氟甲基苯并咪唑-1-亚甲基)-5-巯基-1,3,4-噁二唑(2)在乙醇-水的溶液中反应得到了一系列的含2-三氟甲基苯并咪唑的双噁二唑硫醚3a～3j, 再用硝酸氧化得到相应的亚砜衍生物4a～4j. 化合物的结构经元素分析, IR, ¹H NMR确证.     

吡啶-4-甲酰胺噁二唑化合物的合成及性质研究

以4-吡啶甲酸、芳香醛为原料,经缩合、氧化成环和酰化等反应,合成了4个未见文献报道的吡啶甲酰胺噁二唑类化合物,通过红外、核磁共振和元素分析对化合物的结构进行了表征.研究了这4个化合物的荧光性质和生物活性;荧光测试结果表明Cu2+可以使此系列化合物的荧光猝灭,Zn2+可以增强此系列化合物2-(吡啶-4-甲酰胺基)-5-对甲氧基苯基-1,3,4-噁二唑(2b)的荧光;生物活性测试结果表明这4个化合物对所测的5种病原菌都具有较好的杀菌活性,其中2-(吡啶-4-甲酰胺基)-5-对甲基苯基-1,3,4-噁二唑(2d)对小麦赤霉病菌的抑制活性可达到100%.     

含噁二唑肟醚取代的均三唑水杨醛席夫碱的合成及抗菌活性

4-氨基-5-(4-甲氧苯基)-3-巯基-均三唑(2)在无水乙酸钠作用下与β-氯苯丙酮(3)缩合得氨基三唑硫代苯丙酮(4). 化合物4与盐酸羟胺肟化得羰基肟化物5, 接着与水杨醛缩合得到席夫碱肟6, 用氯甲基噁二唑7a～7e对化合物6的肟羟基醚化得到目标物均三唑噁二唑肟醚1a～1e. 所合成的新化合物结构由元素分析和光谱数据表征, 体外抗菌活性也被试验.     

2,5-取代-1,3,4-噁二唑衍生物的合成与杀菌活性

利用生物活性亚结构拼接原理,将吡啶环、噻唑环引入到1,3,4-噁二唑母体结构中,设计并合成了一系列新型含吡啶(噻唑)的1,3,4-噁二唑衍生物.通过IR,1H NMR,EI-MS及元素分析等方法对所合成的化合物进行了结构表征.代表化合物2-(6-氯吡啶-3-甲硫基)-5-(吡啶-4-基)-1,3,4-噁二唑(I)经单晶X衍射证实了结构.初步测定了所合成化合物的杀菌活性,并比较了在1,3,4-噁二唑母体结构中引入噻唑杂环和引入吡啶杂环后其杀菌活性的差异.结果表明:目标化合物对测试的5种菌均具有一定的杀菌活性,对水稻纹枯病的抑制效果普遍优于对其它菌种的抑制效果;在1,3,4-噁二唑母体结构中引入噻唑杂环比引入吡啶杂环对其杀菌活性更有利.     

4-甲基-苯磺酸-2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯的合成及生物活性研究

合成了12个未见文献报道的4-甲基-苯磺酸2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯, 其结构经元素分析、¹H NMR和IR确证. 初步活性测试结果表明: 部分化合物有较好的杀菌活性.     

Synthesis and antitumor activity of N^1-acetylamino-（5-alkyl/aryl-1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives

A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.     

Synthesis,Crystal Structure and Biological Activity of 2-[(Pyridin-2-yl)methylthio]-1H-benzimidazole Derivatives

In order to discover the novel anti-tumor agents, a series of 2-[(pyridin-2-yl)methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[(3,4-Dimethoxypyridin-2-yl)methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828(16), b = 11.625(2), c = 13.463(2) ?, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.     

<Emphasis Type="Italic">N</Emphasis>-substituted 2-(6-amino-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-oxoacetamides

In reaction of 6-aminouracyles with ethyl oxochloroacetate ethyl 2-(6-amino-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-oxoacetates were obtained, which by further reaction with various amines afforded oxo(pyrimidinyl)acetamides. According to the data of biological tests, the synthesized compounds showed low antibacterial and antitumor activity.     

Synthesis and biological activity of some 3-(4-(substituted)-piperazin-1-yl)cinnolines

A new series of 6-substituted-4-methyl-3-(4-arylpiperazin-1-yl)cinnolines 8-10 were synthesized as potential antifungal agents via intramolecular cyclization of the respective 1-(2-arylhydrazono)-1-(4-arylpiperazin-1-yl)propan-2-ones 5-7, mediated by polyphosphoric acid (PPA). The amidrazones themselves were synthesized via direct interaction of the appropriate hydrazonoyl chlorides 4a-d with the corresponding N-substituted piperazine in the presence of triethylamine. The structures of the new prepared compounds were confirmed by elemental analyses, (1)H-NMR, (13)C-NMR, and ESI-HRMS spectral data. The antitumor, antibacterial, and antifungal activity of the newly synthesized compounds was evaluated.     

Synthesis and Biological Evaluation of Novel Uracil and 5-Fluorouracil-1-yl Acetic Acid-Colchicine Conjugate

A series of novel uracil and 5-fluorouracil-1-yl-acetic acid-colchicine derivatives(6a-6n) was synthesized via coupling uracil and 5-fluorouracil(5-FU) with C-10 analogues of colchicine. The antitumor activities of the target compounds against human hepatocellular carcinoma(BEL7402) cells, human ovary carcinoma(A2780) cells, human lung adenocarcinoma(A549) cells and human breast carcinoma(MCF7) cells were tested in vitro, and the structure-activity relationship(SAR) of the compounds was also studied. The bioassay results demonstrate that most of the tested compounds display significant activity and particularly, compounds 6a, 6e, 6h and 6l show more potent cytotoxic activities than 5-fluorouracil and colchicine. The results show that the new derivatives of colchicine are potential suppressors on human cancer.     

Synthesis, and antitumor activity of some N1-(coumarin-7-yl) amidrazones and related congeners

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC?? values of 20.2 and 9.3 μM, respectively.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料, 经过脱甲基、 烷基化等步骤, 合成了一系列双-β-咔啉衍生物. 目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证. 以顺铂为阳性对照药, 采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7等6株细胞)活性. 结果表明, 化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性, 其半抑制浓度(IC₅₀)值均小于10 μmol/L. 初步构效关系研究表明, 当桥链亚甲基数目为8~10, β-咔啉环上9-丁基或9-异丁基取代时, 化合物的抗肿瘤活性较强.     

N-苯甲酰基-N’-1,3,4-噻二唑-2-基硫脲的合成及生物活性研究

本文以苯甲酸为原料,经酰氯化、酰化反应得到中间体苯甲酰基异硫氰酸酯,再与2-氨基-1,3,4-噻二唑经加成反应合成并表征了10种N-苯甲酰基-N’-1,3,4-噻二唑-2-基硫脲3a-3j。初步生物活性测试结果表明:当浓度为10 mg/L时,3a～3d对小麦生根和发芽有一定的调节活性。当浓度为100 mg/L时,大部分化合物对黄瓜灰霉病菌、黄瓜炭疽病菌、水稻纹枯病菌、水稻稻瘟病菌有明显的抑制活性,而对棉花枯萎病菌的抑制活性较差。目标化合物的取代基会影响其生长调节活性和抑菌活性。结合量化计算结果讨论了化合物结构对抑菌活性的影响。     

Autocatalytic synthesis of 3-ethyl-3-hydroxy-indole-2-ones and their neuroprotection and antitumor activities' evaluation

In this study, a series of 3-ethyl-3-hydroxy-indole-2-ones were synthesized through the addition reaction of Et₂Zn and N-substituted isatin by an autocatalytic process. The synthesized compounds were characterized by NMR spectroscopy and mass spectrometry, and the reaction mechanism was discussed. The antitumor and neuroprotection activities of these compounds were evaluated. The results showed that several compounds display protection activity on H₂O₂-induced apoptosis of PC12 cells, which are more effective than that of (±)-α-tocopherol Vitamin E (VE). Moreover, these compounds also show antitumor activity against A549 and P388 cell lines.