N-芳基-4-(吡啶-2-基)-5-(1H-1,2,4-三唑-1-基)噻唑-2-胺衍生物的合成及生物活性研究

利用Hantzsch反应合成了13个N-芳基-4-(吡啶-2-基)-5-(1H-1,2,4-三唑-1-基)噻唑-2-胺衍生物,所有化合物的结构均经1H NMR,MS及元素分析确证.研究发现,溶剂对不同取代基的目标化合物的合成影响很大.生物活性测试结果表明,化合物均具有一定的杀菌活性.其中,化合物6c对番茄早疫和苹果轮纹、化合物6g对番茄早疫、化合物6h对黄瓜黑腥及化合物6i对苹果轮纹均显示80%以上的杀菌活性.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应,合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m.化合物结构经元素分析,1HNMR,IR和MS进行了表征.抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

1-(4-取代苯基)-4-苯基-5-(2-羟基苄基)氨基-1,2,3-三唑类衍生物的合成及抑菌活性

将邻羟苯基引入1,2,3-三唑结构中, 设计合成了10个1-(4-取代苯基)-4-苯基-5-取代-1,2,3-三唑类衍生物. 首先, 以对位取代的芳胺为原料, 经重氮化、叠氮化、闭环和缩合反应制得1-(4-取代苯基)-4-苯基-5-水杨醛亚胺-1,2,3-三唑类衍生物(3a~3e), 再用硼氢化钠还原制得1-(4-取代苯基)-4-苯基-5-(2-羟基苄基)氨基-1,2,3-三唑类衍生物(4a~4e). 目标化合物的结构经核磁、IR及元素分析确认. 抑菌活性测试表明, 当质量浓度为0.1 mg/L时, 除化合物3e和4e外, 所有化合物对白色念球菌的抑菌率均达95%以上, 对大肠杆菌的抑菌率达85%以上, 具有强抑菌活性, 表明该类化合物在抗菌药物开发方面有重要应用价值.     

4-叔丁基-5-(1,2,4-三唑-1-基)-2-苄亚氨基噻唑的合成、晶体结构和抗菌活性

以履代(口片)吶酮,经1,2,4-三唑取以、溴以、硫脲环合得到4-叔丁基-5-(1,2,4-三唑-1-基)-2-氨基噻唑;再与芳醛缩合合成一系列新4-叔丁基-5-(1,2,4-三唑-1-基)-2-苄亚氨基噻唑(5).用单晶X射线衍射测定了化合物5a的晶体结构.化合物5a的晶体属三斜晶系,空间群以P-1,晶胞参数以:a=0.72749(12)nm,b=0.93463(15)nm,c=1.3398(2)nm,α=70.185(2)°,β=75.669(2)°,γ=73.611(2)°;V=0.8105(2)nm3,Z=2,Dc=1.342g/cm3,F(000)=344,R1=0.0431,wR2=0.1611,S=1.01.生物活性实验结果表明:化合物5c(25mg/L)对小麦赤霉病菌、稻曲病菌、对黄瓜灰霉病菌和稻纹枯病菌的抑制率分别以100%,100%,82.8%和80.3%.化合物5d(25mg/L)对稻纹枯病菌、油菜菌核病菌、小麦赤霉病菌和稻曲病菌的抑制率分别以100%,95.5%,100%和100%.化合物5e(25mg/L)对小麦赤霉病菌的抑制率以100%.5d对小麦赤霉病菌、油菜菌核病菌和水稻纹枯病菌的EC50值分别以1.16,1.38和1.47mg/L.     

(E)-1-取代苯基-3-[4-((E)-(2-(4-苯基噻唑-2-基)腙)甲基)苯基]-2-丙烯-1-酮的合成及PTP1B抑制活性研究

蛋白酪氨酸磷酸酶1B(PTP1B)作为胰岛素和瘦素信号转导通路的负调节因子,已成为治疗糖尿病和肥胖症的潜在靶标.为了寻找非磷酸酯类PTP1B抑制剂,设计、合成了一系列(E)-1-取代苯基-3-[4-((E)-(2-(4-苯基噻唑-2-基)腙)甲基)苯基]-2-丙烯-1-酮(4a～4n),并对化合物进行了PTP1B抑制活性测定.结果显示,所有化合物对PTP1B均显示出较强的抑制活性,其中化合物4h活性最佳,IC50为(2.57±0.50)μmol L-1.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

3-取代硫基-5-(1-羟基苯基)-4H-1,2,4-三唑类化合物的合成及抑菌活性

依据邻羟基二苯醚及三唑类化合物的抗菌特性及生物活性叠加原理, 将邻羟苯基和1,2,4-三唑分子片断有机结合, 设计合成了12个新型3-取代硫基-5-(1-羟基苯基)-4H-1,2,4-三唑类化合物. 首先, 水杨酸甲酯与水合肼反应生成水杨酰肼, 水杨酰肼再与硫氰酸铵和盐酸反应, 生成5-(1-羟基苯基)-4H-1,2,4-三唑-3-硫酮(3), 最后在碱性条件下化合物3与取代苯乙酮、氯苄和碘甲烷发生烷基化反应生成目标化合物, 化合物结构经 1H NMR及IR等表征确认. 抑菌测试结果表明, 当化合物质量分数为0.01%时, 目标化合物对白色念珠菌和大肠杆菌的抑菌率高达90%, 具有强抑菌活性; 对金黄色葡萄球菌的抑菌率高达80%, 具有一定的抑菌活性.     

1-(2′-苯基-1′,2′,3′-三唑-4′-甲酰基)-4-芳基氨基硫脲及其环化产物的合成

以2-苯基-1,2,3-三唑-4甲酰肼为原料合成了几种新的1-(2′-苯基-1′,2′,3′-三唑-4′-甲酰基)-4芳基氨基硫脲,在不同条件下环化,制得一系列新的1,3,4-噻二唑、1,3,4- 二唑和1,2,4-均三唑衍生物.化合物的结构经元素分析、IR、1HMR和MS确证,并对其波谱性质进行了讨论.     

2,2-二甲基-5-取代苯基-3-(1,2,4-三唑-1/4-甲基)-3-戊醇类化合物的合成、表征及生物活性

取代苯甲醛经缩合、催化氢化、环氧化和开环反应合成了9种2,2-二甲基-5-取代苯基-3-(1,2,4-三唑-1-基甲基)-3-戊醇类化合物和2种2,2-二甲基-5-取代苯基-3-(1,2,4-三唑-4-基甲基)-3-戊醇类新化合物. 并对1,2,4-三唑-1-基衍生物和1,2,4-三唑-4-基衍生物的选择性合成进行了研究; 新化合物结构经质谱, ¹H NMR, 元素分析等确证, 并用单晶X射线衍射测定了化合物1a的晶体结构. 生物活性测试结果表明, 部分化合物具有强杀菌活性.     

3-芳基-1-(吡啶-3-基)-2-(1H-1,2,4-三唑-1-基)-2-丙烯-1-醇的合成及生物活性研究

用硼氢化钠还原3-芳基-1-(吡啶-3-基)-2-(1H-1,2,4-三唑-1-基)丙烯酮, 合成了10个新型含吡啶基的三唑醇类化合物. 所有化合物均经核磁、元素分析确证. 生物活性测试结果表明, 部分化合物具有一定的杀菌活性及植物生长调节活性.     

1-(1-Phthalazinyl)- and 1-(4methoxyphenyl)-6,6dimethyl-4oxo-4,5,6,7-tetrahydroindazole

2-(1-Phthalazinylhydrazino)methylene-(IIIa) or 2-(1-phthalazinylhydrazino)ethylidene-5,5-dimethyl-1,3-cyclohexanediones (IIIb) were prepared from 1-hydrazinophthalazine and 2 formyl- or 2-acetyldimedone. Cyclization of IIIb in the presence ofp- TsOH gave 1-(1-phthalazinyl)3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydroindazole. Reaction of 4-methoxyphenylhydrazine with 2 formyl- and 2-acetyidimedone gave the corresponding 1-(4methoxyphenyl)-4-oxo-4, 5, 6, 7-tetrahydroindazole. In the case of 2 -formyldimedone the intermediate 2-(4methoxyphenylhydrazinomethylene)-5, 5-dimethyl-1,3-cyclohexanedione was isolated.Riga Technological University, Riga LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 708–710, May, 1996. Original article submitted December 31, 1995.     

Synthesis of 4-(1-Adamantyl)- and 4-(1-Adamantylmethyl)-substituted Halothiazoles

1-Adamantyl bromomethyl ketone and 1-adamantylmethyl chloromethyl ketone react with potassium thiocyanate in dimethylformamide to give the corresponding thiocyanatoketones which cyclize under the influence of HCl into 4-(1-adamantyl) and 4(-adamantylmethyl)chlorothiazole respectively. 4-(1-Adamantyl)-2-amino-5-bromothiazole and its N-derivative were synthesized by the reaction of 1-adamantyl dibromomethyl ketone with thioureas and N-substituted thiourea in acetonitrile.     

Syntheses and Structural Characterization of 1-（4-Phenyl-2-thiazolyl）-3-（4-methylphenyl）-5-（2-furyl）-4,5-dihydro-（1H）-pyrazole and 1-（4-（4-Fluoro）phenyl-2-thiazolyl）-3-（4-methyl-phenyl）-5-（2-furyl）-4,5-dihydro-（1H）-pyrazole

The title compounds were synthesized and characterized by IR,1H-NMR,Mass and elementary analysis and single-crystal X-ray diffraction.In 1a,intermolecular C-H…π interactions produce a three-dimensional network.In 1b,intermolecular C-H…O hydrogen bonds generate an R22(22) ring.The hydrogen bonding is supported by C-H…π interactions.     

4-(Arylaminothiocarbonyl)-1-(1-o-methoxyphenylcarbamido)-ethylpiperazines as anticonvulsants

Several 4-(arylaminothiocarbonyl)-1-(1-o-methoxyphenylcarbamido)-ethylpiperazines were synthesized and evaluated for their anticonvulsant activity against pentylenetetrazol-induced seizures in mice. The ability of substituted piperazines to inhibit in vitro respiratory activity of rat brain homogenates was also determined to study their structure-activity relationship.     

(E)-1-alkyl-4-

(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S(N)V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO with an activation energy of 14 kcalmol(-1). At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a second-order reaction (k = 4,100 M(-1)s(-1) at 30 degrees C) and gave the corresponding substitution product with an intense long wavelength absorption band (lambdamax=360 nm, epsilon = 27,500 M(-1)cm(-1)). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.     

新型1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物的合成

以二乙醇胺为原料,经溴化、环合、N-烷基化和还原4步反应制得关键中间体——4-[4-(4-甲氧基苯基)哌嗪-1-基]苯胺(4);4与酰氯经酰基化反应合成了11个新型的1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物,其结构经1H NMR,FT-IR,ESI-MS和元素分析表征。