3-(5-取代苯基-［1,3,4］恶二唑-2-亚甲硫基)-5-吡啶-3-基-［1,2,4］三唑-4-胺的合成及抗菌活性

目的研究多杂环化合物的合成方法和抗菌活性。方法用4-氨基-3-吡啶-3-基-［1,2,4］三唑-5-硫醇与5-取代苯基-2-氯甲基-［1,3,4］恶二唑缩合得相应的目标胺类化合物。用平皿试验法，研究了目标化合物的体外抑菌活性。结果合成了12个新化合物，其结构经MS，IR，¹H NMR和元素分析确证。多数化合物在体外表现出较好的抑菌活性。结论含吡啶的恶二唑三唑多杂环化胺类化合物有可能成为新型结构的抗菌药物。     

Synthesis,in vitro cytotoxicity,and anti-microbial studies of 1,4-bis(4-substituted-5-mercapto-1,2,4-triazol-3-yl)butanes

Synthesis and evaluation of cytotoxicity and anti-microbial activity of a series of 1,4-bis(4-substituted-5-mercapto-1,2,4-triazol-3-yl)butane derivatives comprising thioether functionality and other pharmacophore modifications are described. All the newly synthesized compounds were characterized by IR, NMR, elemental analyses, and mass spectral studies. The compounds 4a–f, 5a–f, and 6a–f were evaluated for in vitro cytotoxicity potential using the standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against a panel of three human cancer cell lines: Lung carcinoma A-549, Colon carcinoma HT-29, and Breast Cancer MDA MB-231. All the compounds were subjected to in vitro anti-bacterial activity against Bacillus subtilus (ATCC 6633), Staphylococcus aureus (ATCC-25923), Escherichia coli (ATCC-25922), and Pseudomonas aeruginosa (ATCC-27853) and their minimal inhibitory concentrations were determined.     

Synthesis and biological evaluation of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione as antimycobacterial agents

Resistance among dormant mycobacteria leading to multidrug‐resistant and extremely drug‐resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione derivatives ( 4a–5c ) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC₅₀) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram‐negative and Gram‐positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP‐1, A549, and PANC‐1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.     

Studies on some N-bridged heterocycles derived from bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl] alkanes

A series of bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl] alkanes have been synthesized and were converted into bis-[1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-4-yl] alkanes. The newly synthesized compounds were characterized by analytical IR, NMR and mass spectral studies. Some of the newly synthesized compounds were screened for their antibacterial properties and exhibited activity with MIC in the range 3-12.5 micrograms/ml.     

2-(3-吡啶)-5-{［(5-芳基-1,3,4-二唑-2-基)亚甲基］硫代}-1,3,4-二唑的合成及抗菌活性

目的研究多杂环化合物的合成方法和抗菌活性。方法用［(5-吡啶-3-基-1,3,4-二唑-2-基)硫代］乙酸与相应的芳酰肼缩合,得到相应的目标化合物。用试管稀释法,研究目标化合物的体外抑菌活性。结果合成了16个新化合物,其结构经MS,IR,₁HNMR和元素分析确证。其中多数化合物在体外表现出较好的抑菌活性。结论 含吡啶的双二唑杂环化合物有可能成为新型结构的抗菌药物。     

1,4-双[(5-芳基-1,3,4-噁二唑-2-)亚甲基]哌嗪的合成及其抗菌活性

目的研究多杂环化合物的合成方法和抗菌活性.方法将2-芳基-5-氯甲基-1,3,4-噁二唑(h～1n)与哌嗪缩合得相应的双取代哌嗪目标化合物(2a～2n).用试管稀释法,研究目标化合物的体外抑菌活性.结果合成了14个新化合物,其结构经MS、IR、1H-NMR和元素分析确证.多数化合物在体外表现出较好的抑菌活性.结论双噁二唑杂环取代的哌嗪化合物有可能成为新型结构的抗菌药物.     

2-(3-吡啶)-5-{[(5-芳基-1,3,4-二唑-2-基)亚甲基]硫代}-1,3,4-(口恶)二唑的合成及抗菌活性

目的　研究多杂环化合物的合成方法和抗菌活性。方法　用 [(5 吡啶 3 基 1,3 ,4 二唑 2 基 )硫代 ]乙酸与相应的芳酰肼缩合 ,得到相应的目标化合物。用试管稀释法 ,研究目标化合物的体外抑菌活性。结果　合成了16个新化合物 ,其结构经MS ,IR ,1HNMR和元素分析确证。其中多数化合物在体外表现出较好的抑菌活性。结论含吡啶的双二唑杂环化合物有可能成为新型结构的抗菌药物     

3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-［1,3,4］噁二唑-2-甲基)肟的合成及抗菌活性

目的研究氨基杂环肟类化合物的合成方法和抗菌活性。方法用4-氨基-3-甲基-5-巯基-［1,2,4］三唑与β-氯苯丙酮缩合、肟化、醚化得3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-［1,3,4］噁二唑-2-甲基)肟醚目标化合物。用二倍试管稀释方法研究了目标化合物的体外抑菌活性。结果合成了12个新化合物，其结构经MS，IR，¹H NMR和元素分析确证。10个目标化合物在体外有一定的抗菌活性。结论该类杂环化合物有待进一步的结构优化研究。     

3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-[1,3,4]噁二唑-2-甲基)肟的合成及抗菌活性

目的研究氨基杂环肟类化合物的合成方法和抗菌活性。方法用4-氨基-3-甲基-5-巯基-[1,2,4]三唑与β-氯苯丙酮缩合、肟化、醚化得3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-[1,3,4]噁二唑-2-甲基)肟醚目标化合物。用二倍试管稀释方法研究了目标化合物的体外抑菌活性。结果合成了12个新化合物,其结构经MS,IR,1H NMR和元素分析确证。10个目标化合物在体外有一定的抗菌活性。结论该类杂环化合物有待进一步的结构优化研究。     

Novel 3,6‐Disubstituted 7H‐1,2,4‐Triazolo[3,4‐b][1,3,4]thiadiazines: Synthesis,Characterization, and Evaluation of Analgesic / Anti‐inflammatory,Antioxidant Activities

In this study, the synthesis of a new series of 3,6‐disubstituted‐7H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazine 1a – 4c compounds derived from 4‐amino‐3‐substituted‐1,2,4‐triazole‐5‐thiones 1 – 4 is described. All of the synthesized compounds were screened for their possible analgesic / anti‐inflammatory, antioxidant activities and gastric toxicity. The compound 2c was found to have both significant analgesic and consistent anti‐inflammatory activity without inducing any gastric lesions along with minimal lipid peroxidation. A deep insight into the structures of the active compounds revealed that the compounds carrying an electron withdrawing group (a chloride or fluoride) on the phenyl ring at 6‐position of the condensed heterocyclic derivatives exhibited noticeable higher activity.     

Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones

1,4-Dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-L2,4-triazolinc-5-thiones were synthesized. The structures of original eight compounds were confirmed by elemental analysis, 1H NMR and mass spectral methods. One of the compounds (3a) was tested in vitro for its anticancer activity against 52 human tumor cell lines.     

Synthesis and antituberculosis activity of new N-phenyl-N'-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thioureas

In this study, eight original N-phenyl-N'-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thiourea derivatives were synthesized and tested for antituberculosis activity. Antituberculosis activities of the synthesized compounds were screened in vitro using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv at 6.25 microg/ml. The highest inhibition observed with the synthesized compounds is 67% for N-phenyl-N'-[4-(5-cyclohexylamino-1,3,4-thiadiazole-2-yl)phenyl]thiourea.     

Synthesis of 2-(4-substitutedbenzyl-[1,4]diazepan-1-yl)-n-(1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides as inotropic agents

In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide (6m) was the most potent, increasing stroke volume by 8.38±0.16% (milrinone 2.45± 0.06%) at 3 x 10(-5) m. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.     

Synthesis and antiviral evaluation of novel 5-(N-Aryl-aminomethyl-1,3,4-oxadiazol-2-yl)hydrazines and their sugars, 1,2,4-triazoles, tetrazoles and pyrazolyl derivatives

A number of new N-arylaminomethyl-1,3,4-oxadiazole derivatives 2, 3a,b, and 9-12a,b were prepared. Sugar (5-N-arylaminomethyl-1,3,4-oxadiazol-2-yl) hydrazones 4-6a,b were synthesized by the reaction of the hydrazino derivatives 3a,b with the corresponding monosaccharides. The novel acyclo-C-nucleosides 7, 8a,b were prepared by heterocyclization of the sugar hydrazones 4, 5a,b with acetic anhydride. A number of the synthesized compounds were tested for their antiviral activity against herpes simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV, MBBcell culture-adapted strain). The results revealed that the sugar hydrazones 6a,b showed higher antiviral activity compared to the other hydrazones and their acetylated derivatives.     

Synthesis and cytotoxicity testing of novel 2-(3-substituted-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl)-3-phenyl-4(3H)-quinazolinones

A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to evaluate their cytotoxic activity against 12 human cancer cell lines. The bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level of selectivity for certain cell lines. The most active compounds 9, 10, 15, and 16 showed moderate antiproliferative activity and were approximately 4-fold less potent than cisplatin.     

Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles

A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives, containing the adamantyl moiety, were synthesized and examined in various viral test systems. No antiviral effects were noted with any of the compounds at subtoxic concentrations in cell culture.     

Synthesis and anti-inflammatory activity of derivatives of 5-[(2-disubstitutedamino-6-methyl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2-thiones

Synthesis and results of anti-inflammatory activity in vivo of 5-[(2-disubstitutedamino-6-methyl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2-thiones and their S-alkyl-, N(3)-acyl- and N(3)-aminomethyl derivatives are described. All the tested compounds possess anti-inflammatory activity comparable to that of acetylsalicylic acid and some derivatives of 5-[(6-methyl-2-piperidin-1-yl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2-thione were found to be much more active than ibuprofen.     

叔丁基三唑衍生物的合成及抗真菌活性研究

目的研究具有叔丁基结构的三唑醇类化合物的抗真菌活性以及各种4-(4-烷氧基苯基)哌嗪侧链的引入对抗真菌活性的影响.方法以一氯频那酮、三氮唑为原料,经多步反应合成目标化合物,化合物结构经IR、1H-NMR谱确证;选择8种真菌为实验菌株,按国际标准抗真菌敏感性实验方法测定其体外抗真菌活性.结果设计合成了10个新化合物.10个目标化合物对8种真菌均具有一定的抑制活性,其中,有4个化合物对白色念珠菌的MIC80值小于或等于0.125 mg·L-1,是氟康唑的4倍以上,与伊曲康唑相当.结论可以通过引入更多的疏水基团设计三唑醇类化合物,立体化学因素对该类化合物的体外抑菌活性有较大影响.     

7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物的合成与抗菌活性

目的寻找新型的噁唑烷酮-氟喹诺酮类抗菌药物。方法设计合成了7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物，测定其体外抗菌活性。结果共合成20个目标化合物，经^{1H NMR和MS确证结构。目标化合物具有较好的体外抗菌活性，尤其是化合物22，对屎肠球菌的抑制活性分别是吗啉噁酮和诺氟沙星的16倍和64倍，对金葡菌的抑制活性为吗啉噁酮的4倍。结论某些带有氟喹诺酮结构片段的噁唑烷酮类化合物抗菌活性加强。}