含叔醇结构的新型吡唑-4-甲酰胺类化合物的合成及杀菌活性

在吡唑环的3位引入叔醇结构,设计合成了一系列新颖的吡唑-4-甲酰胺类化合物,其结构经1H NMR, 13C NMR,HR-ESI-MS和X射线衍射表征确证.生物活性测试结果显示,部分化合物在100μg/mL时对瓜果腐霉菌和辣椒疫霉菌等测试植物病原菌显示了一定的杀菌活性,如N-(2-氟苯基)-3-(1-羟基环己基)-1,5-二甲基-1H-吡唑-4-甲酰胺(B1)和N-(噻唑-2-基)-3-(1-羟基环己基)-1,5-二甲基-1H-吡唑-4-甲酰胺(B10)对瓜果腐霉菌的EC50分别为76.3和71.9μg/mL,化合物B10对辣椒疫霉菌的EC50分别为85.4μg/mL.     

新型1,2,4-三唑硫醚取代乙酰胺类化合物的合成及抗菌活性

以3, 4, 5-三甲氧苯甲酸为原料,将具有优良生物活性的1,2,4-三唑与酰胺结构有机结合,通过酯化、肼解、环化、醚化、水解、缩合等反应合成1, 2, 4-三唑硫醚乙酰胺类化合物6a-6m,其结构经1H NMR,13C NMR,MS和元素分析进行了结构确证。初步生物活性测试表明：化合物浓度在50 μg/mL时,化合物6a-6m对猕猴桃软腐病中的葡萄座腔菌、拟茎点霉菌（Phomopsis sp.）和灰霉菌（B. cinerea）表现一定的抑制活性,其中化合物6k和6l对葡萄座腔菌、拟茎点霉菌和灰霉菌的抑制活性在83.4%至91.3 %;化合物6k对葡萄座腔菌和拟茎点霉菌的EC50值为46.6 μg/mL和30.8 μg/mL,均优于对照药剂嘧霉胺(57.6 μg/mL 和 32.1 μg/mL)。以上生物活性表明,1, 2, 4-三唑硫醚乙酰胺类化合物具有较好的抑菌活性,为进一步开发高活性化合物奠定一定基础。     

微波辅助下N-酰胺基-2-(4-氧代-4H-色烯-3-基)噻唑-4-酮类衍生物的平行合成及其杀虫活性

利用微波辅助组合平行合成技术, 色酮酰腙类衍生物与巯基乙酸发生缩合反应, 成功地构建了N-酰胺基-2-(4-氧代-4H-色烯-3-基)噻唑-4-酮类化合物库. 与常规加热方法相比较, 反应时间由原来的8 h缩短至9 min, 且收率大大提高. 同时, 在250 μg/mL下, 检测了其杀虫活性, 初步生物测试结果表明部分化合物对红蜘蛛显示出良好的杀虫活性.     

2-吗啉基-1-丙基-1H-吲哚-3-取代酰腙类化合物的合成及抑菌活性

以2-吲哚酮为先导化合物,设计合成一系列2-吗啉基-1-丙基-1H-吲哚-3-取代酰腙类化合物.目标化合物结构经核磁共振波谱(1H NMR和13C NMR)和高分辨质谱仪(HRMS)进行确证.采用浊度法测试了目标化合物的离体抑菌活性,抑菌活性测试结果表明:目标化合物对柑橘溃疡病菌(Xanthomonas axonopodis pv.Citri,X.citri)、烟草青枯病菌(Ralstonia.Solanacearum,R.solanacearum)和水稻白叶枯病菌(Xanthomonas oryzae pv.Oryzae,X.oryzae)均表现出一定的抑制活性.化合物2-氰基-N'-((2-吗啉基-1-丙基-1H-吲哚-3-基)亚甲基)乙酰肼(12a)、4-氯-N'-((2-吗啉基-1-丙基-1H-吲哚-3-基)亚甲基)苯甲酰肼(12c)、4-氟-N'-((2-吗啉基-1-丙基-1H-吲哚-3-基)亚甲基)苯甲酰肼(12f)、N'-((2-吗啉基-1-丙基-1H-吲哚-3-基)亚甲基)-4-硝基苯甲酰肼(12k)和N'-((2-吗啉基-1-丙基-1H-吲哚-3-基)亚甲基)异烟肼(12m)表现出较好的抑制活性;化合物12a、12c、12f、12k和12m对水稻白叶枯病菌的EC50为73.79、61.94、59.70、36.72和82.79μg/m L,抑制活性优于对照药叶枯唑和噻菌铜(EC50分别为92.4、120.22μg/m L).     

含4(3H)-喹唑啉酮结构的取代1,3,4-噁二唑(噻二唑)化合物的合成及抗菌活性研究

以2-胺基苯甲酸为原料,通过环化、缩合、肼解、环化、硫醚化和氧化等步骤,合成了10个含喹唑啉酮取代1,3,4-噁二唑(噻二唑)化合物。通过1H NMR、13C NMR、MS 和元素分析进行确证其结构。初步抑菌活性测试表明,化合物浓度在50 μg/mL时,对葡萄座腔菌(Botryosphaeria dothidea)、拟茎点霉菌(Phomopsis sp.)和灰霉菌(B. cinerea)具有中等抑制活性。另外,目标化合物对猕猴桃溃疡病(Pseudomonas syringae pv. actinidia)均具有一定的抑制活性,其中化合物6a和6b对猕猴桃溃疡病的EC50值为11.7 μg/mL和20.5 μg/mL,优于对照药剂叶枯唑(24.5 μg/mL)。这类化合物具有较好抗菌的生物活性,在此基础上进行结构优化,有望发现较高活性化合物。     

3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟酯的合成及抑菌活性

以3-甲基吡啶、特戊酸乙酯、盐酸羟胺和取代苯甲酸等为原料,经加成、肟化和酯化反应,合成了12种新型的3,3-二甲基(吡啶-3-基)-丁-2-酮肟酯.该方法反应条件比较温和、收率高.化合物的结构通过IR、~1H NMR、~(13)C NMR和元素分析确证.采用菌丝生长速率法测试了目标化合物对两种病原菌的离体抑制活性,O-(4-溴苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3h)和O-(4-氯苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3j)对菌核菌有较强的抑制活性,EC50值分别为5.07和4.81μg/mL;3h、3j和O-(3,4-二氯苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3l)对灰霉菌显示出较高的抑制活性,EC50值分别为4.98、5.44和6.34μg/mL.     

N-[3-(4-喹唑啉基)氨基-1H-吡唑-4-甲酰基]醛腙类衍生物的合成及抗菌活性研究

以4-氯喹唑啉、3-氨基-4-吡唑甲酸乙酯和芳醛为原料,合成了13个新型的N-[3-(4-喹唑啉基)氨基-1H-吡唑-4-甲酰基]醛腙类化合物,通过IR,1H NMR,13C NMR和元素分析对其结构进行了确认.初步生物活性测试结果表明,在50 μg/mL浓度下,化合物5d对小麦赤霉菌和苹果腐烂菌的抑制率与对照药剂嗯霉灵相当;化合物5k对小麦赤霉菌的抑制率则高于噁霉灵.     

4-(4-吗啉基)-1H-吲唑-3-胺合成方法的改进

2,6-二卤代苯腈(1a-b)和吗啉反应合成了2-卤代-6-(4-吗啉基)苯腈(2a-b),后者环合生成4-(4-吗啉基)-1H-吲唑-3-胺(3)。探索了反应体系中碱的种类、反应溶剂、反应温度以及反应时间对反应的影响,结果表明,2-氟-6-(4-吗啉基)苯腈(2b)在乙酸钠/DMF体系中70℃下反应14 h,化合物3的收率可以达到84.5%。     

新型含吡啶环取代的吡唑肟醚类化合物的合成及生物活性研究

为了寻找新型高效低毒的农药先导化合物,通过N-吡啶基吡唑肟与2-氯-5-氯甲基吡啶的缩合反应,合成了一系列含吡啶环取代的吡唑肟醚类化合物.目标化合物的结构均经1H NMR,13C NMR和元素分析确证.初步生物活性试验结果表明,部分化合物具有一定的杀菌、杀虫和植物生长调节活性.如化合物5e在浓度为50 μtg/mL时对番茄早疫的抑制率为61.4％;化合物5j在浓度为50 μg/mL时对花生褐斑的抑制率为60.2％;化合物5i在浓度为500 μg/mL时对蚜虫表现出50.3％的杀死率;化合物5f在浓度为10 μg/mL时对黄瓜子叶生根表现出71.0％的促进生长作用.     

2-(吡啶-2-甲酰基)嘧啶类化合物的合成与生物活性研究

在2-苯甲酰基嘧啶类化合物结构优化结果基础上,定向设计合成了8个2-(吡啶-2-甲酰基)嘧啶类化合物,并对其进行了室内杀菌活性测定,结果表明这类化合物对黄瓜白粉病和黄瓜霜霉病有很好的防效.对高活性化合物6b深入筛选结果表明:6b对黄瓜白粉病有较好的预防和治疗活性,预防活性的EC50和EC90值分别为0.69和2.89 mg/L,治疗活性EC50和EC90值分别为0.13和1.6 mg/L,与对照药剂苯菌酮相当.2-氯-N-{[2-(4,6-二甲氧基嘧啶-2-甲酰基)吡啶-3-基]氧基}-N-甲基苯甲酰胺(6b)具有向上传导活性和较好的耐雨淋作用,持效期为15~20 d.     

Novel quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety as potential bactericides and fungicides: Design,synthesis, characterization and 3D-QSAR analysis

A series of quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety were designed, synthesized and evaluated for their biological activities against phytopathogenic microorganisms. Antimicrobial bioassays in vitro indicated that most of the target compounds exhibited more significant antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) than the agricultural bactericide thiadiazole-copper. A comparative molecular similarity index analysis (CoMSIA) model with cross-validated q² and non-cross-validated r² values of 0.561 and 0.882 was generated to investigate the structure-activity relationships of title compounds against Xoo. Title compound 6w, which was rationally designed under the guidance of obtained CoMSIA model, exhibited the excellent anti-Xoo effect in vitro with an EC₅₀ value of 29.10 μg/mL, which is approximately 3-folds more effective than thiadiazole-copper (113.93 μg/mL). In addition, compound 6i demonstrated the impressive antifungal effects against Rhizoctonia solani (Rs) and Fusarium graminearum (Fg) in vitro, with the corresponding EC₅₀ values of 11.01 μg/mL and 36.00 μg/mL, which is obviously better than the agricultural fungicide hymexazol (76.74 μg/mL and 56.19 μg/mL, respectively). The above researches indicate that quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety could be further studied as template molecules of novel agricultural microbicides.     

Synthesis and biological evaluation of 4-methyl-1,2,3- thiadiazole-5-carboxaldehyde benzoyl hydrazone derivatives

To find new lead compounds with high biological activity,a series of novel 4-methyl-1,2,3-thiadiazole-5-carboxaldehyde benzoyl hydrazone derivatives were designed and synthesized.Their structures were confirmed by ~1H NMR,~(13)C NMR,IR spectrum and elemental analysis.Preliminary bioassay indicated that the title compounds exhibited moderate to strong fungicidal activity against six fungi in vitro at50 μg/mL.Moreover,some of the title compounds exhibited good curative activity against TMV in vivo at500 μg/mL.The structure-activity relationship analysis of compounds against Valsa mali showed that compounds containing halogen at the para position on phenyl exhibited the best activity.Especially compound 8k showed broad spectrum fungicidal activities against Valsa mali,Botrytis cinerea,Pythium aphamdermatum,Rhizoctonia solani,Fusarium moniliforme and Altemaria solani with the EC_(50) values of8.20,24.42,15.80,40.53,41.48,and 34.16 μg/mL,respectively.     

Synthesis and anti-fungal activity of seven oleanolic acid glycosides

In order to develop potential anti-fungal agents, seven glycoconjugates composed of α-L-rhamnose, 6-deoxy-α-L-talose, β-D-galactose, α-D-mannose, β-D-xylose-(1→4)-6-deoxy-α-L-talose, β-D-galactose-(1→4)-α-L-rhamnose, β-D-galactose-(1→3)-β-D-xylose-(1→4)-6-deoxy-α-L-talose as the glycone and oleanolic acid as the aglycone were synthesized in an efficient and practical way using glycosyl trichloroacetimidates as donors. The structures of the new compounds were confirmed by MS, 1H-NMR and 13C-NMR.Preliminary studies based on means of mycelium growth rate, indicated that all the compounds possess certain fungicidal activity against Sclerotinia sclerotiorum (Lib.) de Bary, Rhizoctonia solani Kuhn, Botrytis cinerea Pers and Phytophthora parasitica Dast.     

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.     

N-(取代)对三氟甲基苯基-1,3,5-三取代吡唑-4-酰胺衍生物的合成与生物活性

设计合成10个未见文献报道的N-对三氟甲基苯基-1,3,5-三取代吡唑-4-酰胺类化合物, 其结构经元素分析, ¹H NMR, IR 确证. 初步生物活性测试结果表明, 部分化合物对水稻纹枯病、小麦赤霉病、辣椒枯萎病和马铃薯晚疫病有一定的杀菌活性.     

Synthesis and anti-TMV activity of novel N-(3-alkyl-1H-pyrazol-4-yl)-3-alkyl-4-substituted-1H-pyrazole-5-carboxamides

In order to investigate the biological activity of novel bis-pyrazole compounds,a series of N-（3-alkyl-5-（N-methylcarbamyl）- 1H-pyrazol-4-yl）-3-alkyl-4-substituted-1H-pyrazole-5-carboxamides were designed and synthesized with ethyl 3-alkyl-1H-pyrazole -5-carboxylate 1 as starting materials.N-Methyl-3-alkyl-4-amino-1H-pyrazole-5-carboxamides 6 were obtained from 1 via 5 steps.3-Alkyl-4-substitued-1H-pyrazole-5-carboxyl chlorides 4a,4b,11a,11b,11c or 12 were also obtained from 1 via several steps.Target compounds 7a-7g were obtained after the reaction of 6 with the above 1H-pyrazole-5-carboxyl chlorides.Preliminary bioassay showed some compounds possessing good inactivation effect against TMV（tobacco mosaic virus）.Compound 7a showed higher activity superior to ningnanmycin at a concentration of 5.0×10^-4 g/mL and equal activity at 1.0×10^-4 g/mL;7b and 7c showed equal activity to virazole both at concentrations of 5.0×10^-4 g/mL and 1.0×10^-4 g/mL.     

Catalyst- and solvent-free coupling of 2-methyl quinazolinones and 3-(trifluoroacetyl)coumarins: An environmentally benign access of quinazolinone derivatives

An environmentally benign highly atom-economic protocol for the construction of the CC bond has been developed under catalyst- and solvent-free conditions. This protocol involves the efficient coupling of 2-methyl quinazolinones with 3-(trifluoroacetyl)coumarins for the access of quinazolinone derivatives in excellent yields (up to 90 %). The crystal structure of compound 3di was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the quinazolinone derivatives against Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Phytophthora parasitica var nicotianae, and Rhizoctonia solani Kuhn, were investigated. The bioassay results indicated that most of the target products exhibited promising fungicidal activities, and compound 3 cl exhibited 95 % fungicidal activity against R. solani, with an EC₅₀ value of 10.6 μg/mL.     

A Novel Molecule: 1-(2,6 Dichlorobenzyl)-4-(2-(2-4-hydroxybenzylidene)hydrazinyl)pyridinium Chloride and its Interaction with DNA

Herein, a novel pyridine derivative, 1-(2,6 dichlorobenzyl)-4-(2-(2-4-hydroxybenzylidene)hydrazinyl)-pyridinium chloride (DHPC), was synthesized as a candidate drug molecule. Interaction of DHPC with DNA was used to explore its effect on DNA via Differential Pulse Voltammetry, Cyclic Voltammetry, and Electrochemical Impedance Spectroscopy. We demonstrated that oxidation signal of guanine bases of DNA decreased significantly while that of DHPC increased after its interaction with one another. Our candidate drug molecule exhibits LOD and LOQ, e.g., 1.5 μg/mL and 4.9 μg/mL, respectively. Toxicity effect value for DHPC (S%) was calculated as %31, demonstrating the candidate drug molecule's toxic effect on DNA.     

Synthesis and biological evaluation of 2-(3-fluoro-4-nitro phenoxy)-n-phenylacetamide derivatives as novel potential affordable antitubercular agents

A novel series of 2-(3-fluoro-4-nitrophenoxy)-N-phenylacetamide compounds were designed, synthesized and in vitro assessed for their antitubercular activities by a microdilution method. All the novel derivatives exerted potent or moderate active against M. tuberculosis H??Rv, with MIC values ranging from 4 to 64 μg/mL. The most potent derivative 3m showed an identical MIC value of 4 μg/mL for both M. tuberculosis H??Rv and rifampin-resistant M. tuberculosis 261. It demonstrated no inhibitory effects against six different tumor cell lines by a MTT assay and had a good safety profile in a vero cell line, providing a good lead for subsequent optimization in search of novel affordable antitubercular agents.