2-氰基-3-取代丙烯酸(2-乙氧基乙基)酯的合成及除草活性

设计并合成了11个2-氰基-3-取代苯胺基-3-甲硫基丙烯酸(2-乙氧基乙基)酯(2)和11个2-氰基-3-取代苯基脲基丙烯酸(2-乙氧基乙基)酯(5)两类光合作用光系统Ⅱ(PSⅡ)电子传递抑制剂,目标化合物的结构均经1H NMR,13C NMR和质谱分析确证,生物活性测试结果表明:部分化合物2对双子叶杂草表现出良好的选择性和除草活性,化合物5苯环上间位有取代基时有一定的除草活性.     

N-(4'-取代嘧啶-2'-基)-2-甲氧羰基-5-(取代)苯甲酰胺基苯磺酰脲化合物的合成及除草活性研究

为进一步寻找高效、安全和对环境更加友好的除草剂, 以商品化除草剂单嘧磺酯为研究基础, 对其结构中的苯环5-位取代基作了结构修饰, 合成了26个未见文献报道的新型N-(4'-取代嘧啶-2'-基)-2-甲氧羰基-5-苯甲酰胺基苯磺酰脲化合物, 通过¹H NMR、质谱及元素分析确定了化合物的结构. 经油菜平皿法及盆栽法测试了所有化合物的除草活性, 结果表明, 当苯环5-位取代基为苯甲酰胺时, 活性较好, 其对双子叶植物的除草活性与商品化的甲嘧磺隆相当.     

N-(4''''-取代嘧啶-2''''-基)-2-甲氧羰基-5-(取代)苯甲酰胺基苯磺酰脲化合物的合成及除草活性研究

为进一步寻找高效、安全和对环境更加友好的除草剂,以商品化除草剂单嘧磺酯为研究基础,对其结构中的苯环5-位取代基作了结构修饰,合成了26个未见文献报道的新型N-(4'-取代嘧啶-2-基)-2-甲氧羰基-5-苯甲酰胺基苯磺酰脲化合物,通过1H NMR、质谱及元素分析确定了化合物的结构.经油菜平皿法及盆栽法测试了所有化合物的除草活性,结果表明,当苯环5-位取代基为苯甲酰胺时,活性较好,其对双子叶植物的除草活性与商品化的甲嘧磺隆相当.     

N-(4-取代嘧啶-2-基)苄基磺酰脲和苯氧基磺酰脲的3D-QSAR研究

采用比较分子力场分析(CoMFA)方法,对两类单取代嘧啶类似物、6个N-(4-取代嘧啶-2-基)-2-甲氧羰基苄基磺酰脲(1a～1f)和14个N-(4-取代嘧啶-2-基)-2-取代苯氧基磺酰脲(2a～2n)进行三维定量构效关系(3D-QSAR)研究.建立了一个较为可靠的预测模型.结果表明,分子中苯环邻位、嘧啶环形成氢键的N原子处以及嘧啶环4位和6位附近负电荷增加;苯环邻位乙氧基的CH₂CH₃附近选择带正电的原子;苯环邻位乙氧基附近空间体积增加,而嘧啶环4位甲氧基稍远处取代基的立体位阻不超过此位置,将有利于提高活性.最后解释了修饰磺酰脲的除草剂仍具有较高活性的原因.     

3-杂环基硫取代-1,3,4,5-四氢-2-氧代-苯并氮杂衍生物的合成

以芳酰肼为原料, 合成了一系列3-巯基-5-芳基-1,2,4-三唑、2-巯基-5-芳基-1,3,4-噁二唑和2-巯基-5-芳 基-1,3,4-噻二唑, 并通过硫原子对3-溴-2-氧代-苯并氮杂3-位上的亲核取代反应将杂环化合物引入了苯并氮杂的结构当中, 合成了32个新的苯并氮杂杂环衍生物. 为提高其在有机溶剂中的溶解性, 在苯并氮杂的N原子上引入乙酸乙酯和乙酸叔丁酯基取代基, 合成了36个新衍生物. 所有化合物经质谱、核磁共振谱及元素分析确证了结构并初步测定了抗菌活性.     

3-(5′-乙氧基-1,3,4-噻二唑-2′-亚甲氨基)-2-氰基-3-取代-丙烯酸酯类化合物的合成、晶体结构及生物活性

采用氰基丙烯酸酯与5-乙氧基-1,3,4-噻二唑-2-甲氨在乙醇中加热回流的方法合成了一系列3-(5′-乙氧基-1,3,4-噻二唑-2′-亚甲氨基)-2-氰基-3-取代-丙烯酸酯类化合物.目标化合物结构均经1HNMR和元素分析确证.生物活性测试结果表明,部分化合物对双子叶杂草油菜和苋菜显示出较好的除草活性及良好的选择性,用化合物6j在600g/ha剂量下对油菜和苋菜茎叶进行处理,抑制率仍达100%和95.2%,与对照样B相当;氰基丙烯酸酯3位取代基体积对除草活性影响较大,3位为异丙基时活性最高.     

3-杂环基硫取代-1,3,4,5-四氢-2-氧代-苯并氮杂衍生物的合成

以芳酰肼为原料,合成了一系列3-巯基-5-芳基-1,2,4-三唑、2-巯基-5-芳基-1,3,4-噁二唑和2-巯基-5-芳基-1,3,4-噻二唑,并通过硫原子对3-溴-2-氧代-苯并氮杂3-位上的亲核取代反应将杂环化合物引入了苯并氮杂的结构当中,合成了32个新的苯并氮杂杂环衍生物.为提高其在有机溶剂中的溶解性,在苯并氮杂的N原子上引入乙酸乙酯和乙酸叔丁酯基取代基,合成了36个新衍生物.所有化合物经质谱、核磁共振谱及元素分析确证了结构并初步测定了抗菌活性.     

3-取代苯氧甲基-4-氨基-1,2,4-三唑-5-硫酮席夫碱的合成、结构表征和生物活性研究

以醋酸为反应溶剂和催化剂,用自制的4-氨基-4,5-二氢-3-取代苯氧甲基-1,2,4-三唑-5-硫酮与4-氟苯甲醛反应合成了5个4-氨基-4,5-二氢-3-取代苯氧甲基-1,2,4-三唑-5-硫酮席夫碱化合物,通过1HNMR、IR和元素分析对所有化合物进行了结构表征.初步生物活性测试结果表明所有化合物具有优良的杀菌活性,并对席夫碱结构与活性的关系进行了探讨.     

2-苯甲酰基嘧啶类化合物的合成与生物活性

2-嘧啶氧基-N-芳基苄胺类化合物结构经过两次骨架结构优化后得到2-苯甲酰基嘧啶类化合物二次先导结构.在二次先导结构基础上,共设计并合成了36个化合物,所有化合物结构经1H NMR、13C NMR、HRMS确认,并进行了室内杀菌活性筛选,对各部位取代基进行了逐次优化.结果表明2-苯甲酰基嘧啶类化合物中R1取代基以2位卤素或烷基取代的苯环或杂环活性最好;中间苯环6位引入氟原子活性保持;嘧啶环4,6位甲氧基取代活性较好,5位甲基取代活性大大降低;羰基被还原为羟基后活性消失.其中2,3-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHl)、2,5-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHn)及N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)-3-氟苯氧基]-N,2-二甲基苯甲酰胺(4AFd)对黄瓜白粉病的杀菌活性与对照样苯菌酮相当.     

苯环2-位不同酯基取代的磺酰脲类化合物的合成及其除草活性

以正在开发的磺酰脲类超高效除草剂NK94827[N'-(4'-甲基嘧啶-2'-基)-2-甲氧羰基苯磺酰脲]的基本结构为基础,设计合成了18个苯环2位不同酯基取代的的新型磺酰脲类化合物,产物结构均经¹HNMR及元素分析确证.经油菜平皿法和盆栽试验测试除草活性,所合成的部分磺酰脲化合物的除草活性高.     

含1,2,4,5-四取代苯基的吡唑-4-甲酰胺类化合物的设计、 合成及生物活性

通过活性亚结构拼接的方法, 设计合成了一系列含四取代苯基的吡唑-4-甲酰胺类化合物, 所有化合物的结构均通过高分辨质谱（HRMS）和核磁共振氢谱（¹H NMR）确证. 生物活性测试结果表明, 部分化合物对苹果纹轮病菌、 水稻纹枯病菌、 油菜菌核病菌和黄瓜灰霉病菌表现出较好的杀菌活性. 化合物5c表现出较广的杀菌谱, 在浓度为50 μg/mL时对苹果纹轮病菌的抑制活性高达95.5%. 初步构效关系分析发现, 吡唑环N取代基为甲基或叔丁基时, 化合物表现出较好的活性; 含并环结构的化合物5′杀菌活性低于含单个苯环的化合 物5; 苯环取代基R²为低于4个碳的脂肪链时, 化合物杀菌活性更高.     

新型取代苯基噁唑类化合物的设计、合成及生物活性

通过活性亚结构拼接方法,将具有生物活性的噁唑基团与咪唑烷或噻唑烷拼接,设计合成了一系列新型取代苯基噁唑类化合物.以取代的苯甲酸为原料,经过3步反应制得目标化合物,其结构经核磁共振及元素分析确证.初步生物测定结果表明,部分化合物对小麦赤霉病、水稻纹枯病、黄瓜灰霉病和番茄早疫病表现出明显的抑制活性,尤其是化合物5q表现出较广的杀菌谱,且活性与多氧霉素相当.初步构效关系分析发现,苯环上取代基的类别和位置对活性有影响,其中卤素取代基对活性有利,邻位取代优于对位和间位取代.     

Design,synthesis and SAR study of novel sulfonylurea derivatives containing arylpyrimidine moieties as potential anti-phytopathogenic fungal agents

Three series of novel sulfonylureas (SUs) 9-11 containing aromatic-substituted pyrimidines were designed and synthesized. The 3D-QASR and molecular docking studies showed that SUs should be considered as potential antiphytopathogenic fungal agents.     

Design,synthesis and SAR study of novel sulfonylurea derivatives containing arylpyrimidine moieties as potential anti-phytopathogenic fungal agents

Acetohydroxyacid synthase(AHAS) was considered as a promising target for antifungal agents.Herein,three series of novel sulfonylureas(SUs) 9-11 containing aromatic-substituted pyrimidines were designed and synthesized according to pharmacophore-combination and bioisosterism strategy.The in vitro fungicidal activities against ten phytopathogenic fungi indicated that most of the title compounds exhibited broad-spectrum and excellent fungicidal activities.Based on the preliminary fungicidal activities,a CoMFA model was constructed and the 3 D-QSAR analysis indicated that either a bulky group around the 5-position of the pyrimidine ring or electropositive group around the 2-position of the benzene ring would be favour to fungicidal activities.In order to study interaction mechanism,10 k was automatically docked into yeast AHAS and it further indicated that bearing bulky groups-aryl at the pyrimidine ring was critical to enhance antifungal activities.It revealed that the antifungal activity of derivatives 9-11 probably results from the inhibition of fungal AHAS.Thus,the present results strongly showed that SUs should be considered as lead compounds or model molecules to develop novel antiphyt o pathogenic fungal agents.     

Synthesis and herbicidal activity of O,O-dialkyl phenoxyacetoxyalkylphosphonates containing fluorine

A series of substituted phenoxyacetoxyalkylphosphonates bearing fluorine were designed and synthesized. All the new compounds were identified by elemental analysis, IR, ¹H NMR and MS and were tested for herbicidal activity in greenhouse at a rate of 1.5 kg/ha. The results of preliminary bioassay showed that fluorine moiety introduced to the core structure could help to improve the herbicidal activity, and compounds with a 3-trifluoromethyl in benzene ring exhibited higher inhibitory activity.     

N-邻羟苄基氨基酸的合成、表征及抑菌活性

将水杨醛、溴代水杨醛及二溴代水杨醛分别与4种L-α-氨基酸进行缩合反应生成相应席夫碱,不经分离直接加硼氢化钠将其还原制得N-邻羟苄基氨基酸类化合物(3)。 化合物的结构经IR、¹H NMR和元素分析测试技术表征确认。 测得化合物3在质量分数为0.05%时,对金黄色葡萄球菌的抑菌率为100％,对白色念珠菌有较强的抑菌活性,对大肠杆菌有一定的抑菌活性。 氨基酸的碳链R的结构是影响化合物抑菌活性的关键因素,不同烷基R对白色念珠菌和大肠杆菌抑菌活性增强的顺序为CH(CH₃)₂＞CH₃,CH₂CH(CH₃)₂＞H,苯环上引入溴原子对目标化合物的抑菌活性影响不明显。     

新型含巴比妥酸的芳香酰腙类化合物的合成、晶体结构及抑菌活性

在微波辅助下,1,3-二甲基-5-醛基巴比妥酸与芳氧基/芳胺基乙酰肼及含氮杂环乙酰肼缩合制备新型酰腙化合物,并对其抑菌活性进行评价的研究。 新化合物的结构经过元素分析、红外光谱、核磁共振谱、质谱和X射线单晶衍射等技术手段确认。 体外的抑菌活性实验显示,部分目标化合物呈现出优于环丙沙星的抑菌活性。 经过构效关系分析表明,当芳基为含氮杂环时,所形成的化合物抗菌活性与芳基为苯环时相比明显较强,抑菌活性最强的酰腙化合物2t对金黄色葡萄球菌的最小抑菌浓度(MIC)值为0.8 g/L,对大肠杆菌的最小抑菌浓度(MIC)值为1.6 g/L。     

Anthranilic acid-based inhibitors of phosphodiesterase: design, synthesis, and bioactive evaluation

Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which potently inhibited superoxide (O(2)˙(-)) generation induced by formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in human neutrophils. In an attempt to improve their activities, a series of anthranilic acid derivatives were synthesized and their anti-inflammatory effects and underlying mechanisms were investigated in human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most potent inhibitory effect on FMLP-induced release of O(2)˙(-) in human neutrophils with IC(50) values of 0.20, 0.16, 0.15, 0.06, and 0.29 μM, respectively. SAR analysis showed that the activities of most compounds were dependent on the ester chain length in the A ring. Conversely, a change in the linker between the A and B ring from amide to sulfonamide or N-methyl amide, as well as exchanges in the benzene rings (A or B rings) by isosteric replacements were unfavorable. Further studies indicated that inhibition of O(2)˙(-) production in human neutrophils by these anthranilic acids was associated with an elevation in cellular cAMP levels through the selective inhibition of phosphodiesterase 4. Compound 49 could be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases.     

Synthesis,crystal structure and 3D-QSAR studies of antifungal (bis-)1,2,4-triazole Mannich bases containing furyl and substituted piperazine moieties

This article exhibited the synthesis, crystal structure and 3D-QSAR studies of antifungal furyl- and piperazine- containing (bis-)1,2,4-triazole Mannich bases.     

Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758.

Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R-102557 were examined. Variation of the length of the chain between the dioxane ring and the phenyl ring revealed that the linkage with two double bonds is the most preferable. When a cyano group was introduced to the C4 position on the benzene ring, MICs improved further. A fluorine atom was introduced to obtain CS-758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4-methylbenzonitrile using the Horner-Wadsworth-Emmons reaction.