N-[5-(2-氯苯基)-2-呋喃甲酰氨基硫羰基]-L-α-氨基酸乙酯的合成与生物活性测定

设计并合成了9种未见文献报道的N-(5-邻氯苯基-2-呋喃甲酰氨基硫羰基)-L-α-氨基酸乙酯衍生物,其结构经IR,1H NMR,MS和元素分析测试确证.MTT法测试结果表明大部分目标化合物对白血病K562细胞系的增殖具有明显的抑制作用.     

N-[5-(2-氯苯基)-2-呋喃甲酰氨基硫羰基]-L-α-氨基酸乙酯的合成与生物活性测定

设计并合成了9种未见文献报道的N-(5-邻氯苯基-2-呋喃甲酰氨基硫羰基)-L-α-氨基酸乙酯衍生物, 其结构经IR, ¹H NMR, MS和元素分析测试确证. MTT法测试结果表明大部分目标化合物对白血病K562细胞系的增殖具有明显的抑制作用.     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

N-(安替比林-4-基)-N'-取代芳甲酰基硫脲的合成及其生物活性

合成了12个含安替比林基的取代芳甲酰基硫脲类化合物,用1H NMR,IR和元素分析确证了它们的结构,并进行了室内生物活性测试.生测实验证明部分酰基硫脲类化合物,比如N-(安替比林-4-基)-N'-m(或o)-甲苯甲酰基硫脲,N-(安替比林-4-基)-N-o-硝基苯甲酰基硫脲,N-(安替比林-4-基)-N'-m(或p)-氯苯甲酰基硫脲,具有一定的细胞分裂素活性.     

2-(2-(5-氟尿嘧啶-1-基)乙酰氨基)丙酸的合成及表征

以5-氟尿嘧啶-1-基乙酸为原料,N,N-二异丙基碳二亚胺(DIC)/1-羟基苯并三氮唑(HOBt)为缩合剂,分别与L-丙氨酸甲酯和D-丙氨酸甲酯通过液相偶联合成了(S)-和(R)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H) -基)乙酰氨基)丙酸甲酯对映体,收率分别为82％和80％;室温下将化合物水...     

N-苄氧甲酰基(苯)丙氨酸取代苯基酯的合成及生物活性测定

采用N,N’-二环已基酰二胺(DCC)和吡啶, 以及DCC和4-(N,N-二甲氨基)吡啶(DMAP)分别形成的脱水缩合体系, N-苄氧甲酰基氨基酸和酚发生缩合反应生成了一系列结构新颖的N-苄氧甲酰基(苯)丙氨酸取代苯基酯. 在DCC/DMAP体系中的反应产率大于在DCC/吡啶中的产率. 用1H NMR, 13C NMR, IR, MS和元素分析对目标化合物的结构进行了表征. 对合成的目标化合物进行了初步的生物活性测试, 结果表明目标化合物具有一定的杀菌活性和杀虫活性, 杀菌活性高于杀虫活性. DL-丙氨酸芳基酯比相应的L-丙氨酸芳基酯的杀蚜虫活性要高.     

4-(N-甲酰基-N′-邻氯苯基硫脲)-N-邻氯苯基苯氧乙酰胺的核磁共振研究

在超声波辐射下,以PEG-400为固-液相转移催化剂,用邻氯苯胺与双酰基异硫氰酸酯反应,合成出了一种新的化合物——4-(N-甲酰基-N′-邻氯苯基硫脲)-N-邻氯苯基苯氧乙酰胺。实验中观察到了取代和加成反应的竞争。利用元素分析,1H、13C、APT及二维核磁共振技术确定了所合成的新化合物的结构。给出了该化合物的化学位移数据。所得的结果对这类化合物的结构解析很有价值。     

一种新的选择性氧化苏-（1S，2S）-2-（N，N-二甲胺基）-1-（对硝基苯基）-1，3-丙二醇的N-甲基为N-甲酰基的方法

报告多官能团化合物苏—(1S，2S)—2—(N，N-二甲胺基)—1—(对硝基苯基)—1，3—丙二醇与聚合物支载条件下的溴试剂发生的—种新的选择性N-甲基氧化为N-甲酰基的反应．在Na2HPO4存在下，苏—(1S，2S)—2—(N，N-二甲胺基)—1—(对硝基苯基)—1，3．丙二醇于水—CCL4体系中被717阴离子交换树脂支载的溴在60℃氧化24h给出51％收率的苏—(1S，2S)—2—(N-甲基—N—甲酰胺基)—1—(对硝基苯基)-1，3-丙二醇.这种选择性N—甲基氧化为N-甲酰基的反应在2—氨基—1，3—丙二醇衍生物化学中是第—次观察到．     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应（英文）

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%～83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经~1H NMR, ~(13)C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-((N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL~(-1)浓度时4-((N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-((N-2,2-二氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

新型N-取代苯基-2-吡唑基烟酰胺类化合物的合成及其生物活性

基于含吡啶基吡唑的邻甲酰氨基苯甲酰胺类农药分子结构,采用"酰基移位"的策略,以2-氯-3-氰基吡啶和4-溴吡唑或3,5-二甲基吡唑为起始原料,简便合成了14个结构新颖的N-取代苯基-2-吡唑基烟酰胺类目标化合物.通过1H NMR、13CNMR和HRMS对新化合物进行了结构表征.初步生物活性测试结果表明,目标化合物在200mg/L浓度下大多具有明显的杀虫活性,其中N-[4-氯-2-(乙氨基甲酰基)-6-甲基苯基]-2-(3,5-二甲基-1H-吡唑-1-基)烟酰胺(Il)对东方粘虫(MythimnaseparataWalker)具有70%的致死率;部分化合物在50mg/L浓度下对苹果轮纹病菌(Physalospora piricola)和番茄早疫病菌(AlternariasolaniSorauer)表现出较好的杀菌活性,其中2-(4-溴-1H-吡唑-1-基)-N-[2-(环丙氨基甲酰基)-4-碘-6-甲基苯基]烟酰胺(If)和2-(4-溴-1H-吡唑-1-基)-N-[4-氯-2-(乙氨基甲酰基)-6-甲基苯基]烟酰胺(Ih)对苹果轮纹病菌的抑制率分别达到62.9%和54.3%,2-(4-溴-1H-吡唑-1-基)-N-[4-氯-2-(正丙氨基甲酰基)苯基]烟酰胺(Id)对番茄早疫病菌具有54.5%的抑制率.研究结果为今后新型2-吡唑基烟酰胺类衍生物的深入研究提供了重要参考信息.     

A Novel Route to Acyl Ureas: Syntheses of N-[5-(2-Chlorophenyl)-2-Furoyl]-N'-Arylthioureas and Ureas

A novel route to acyl ureas is described. Reaction of 5-(2-chlorophenyl)-2-furoyl chloride with ammonium thiocyanate first, then arylamine under phase transfer catalysis gives N-[5-(2-chlorophenyl)-2-furoyl]-N'-arylthioureas (1a-o). Compounds 1a-o on oxidation with potassium iodate respectively under reflux result in the formation of N-[5-(2-chlorophenyl)-2-furoyl]-N'-arylureas (2a-o).     

3-(4-氯苯基)-6-取代苯氧乙酰氨基均三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成

将取代苯氧乙酰氨基引入到3,6-二取代均三唑并噻二唑的分子骨架中, 设计合成了8个未见文献报道的3-(4-氯苯基)-6-取代苯氧乙酰氨基均三唑并[3,4-b]-1,3,4-噻二唑类化合物5a～5h, 结构经元素分析、IR和¹H NMR等测试得到确证.     

Preparation of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)-5-methoxybenzo[b]furan derivatives and their leukotriene B(4) inhibitory activity

A series of 3-(4-chlorophenyl)-2-(2-aminothiazol-4-yl)benzo[b]furan derivatives 6-10 were prepared and their leukotriene B(4) inhibitory activity was evaluated. We found that several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors. Among them, 3-(4-chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 9b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252.     

2-芳胺基-5-[5'-氨基-1'-(4"-氯苯基)-1',2',3'-三唑-4'-基]-1,3,4-噻二唑的合成

1-[5'-氨基-1'-(4"-氯苯基)-1,2,3-三唑-4'-甲酰基]-4-芳基-3-氨基硫脲在浓硫酸催化下环化得到2-芳胺基-5-[5'-氨基-1'-(4"-氯苯基)-1',2',3',-三唑-4'-基]-1,3,4-噻二唑2a-i, 依此法合成了九个标题化合物, 收率为30-74%。化合物2i的结构用X-光衍射单晶分析确证。     

Synthesis and cytotoxic activity of some novel N-pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives

A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. The results indicated that the compound 2-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl)-N-(6-(4-(4-methoxybenzyl)piperazin-1-yl)pyridin-3-yl)acetamide (5l), with slightly higher inhibition on VEGFR2 than 5a (5.72% and 3.76% inhibitory rate at 20 μM, respectively), was a potential inhibitor against MDA-MB-231 (IC(50) = 1.4 μM) compared with sorafenib (IC(50) = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC(50) = 22.6 μM).     

QSAR Study on Some N-[5-（2-Furanyl）-2-methyl- 4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-Substituted-5-（2-furanyl）-2-methyl-3H-thieno- [2,3-d]pyrimidin-4-ones Using Three-dimensional Holographic Vector of Atomic Interaction Field

Study on the quantitative structure-activity relationship （QSAR） of 26 compounds, N-[5-（2-furanyl）-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted- 5-（2-furanyl）-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones, with three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） was carried out. SMR-PLS QSAR models have been created and good correlation coefficients and cross-validated correlation coefficients were obtained. The result shows that the models have good prediction capability and favorable stability and the 3D-HoVAIF is applicable to the molecular structural characterization and biological activity prediction.     

Identification of novel alpha-glucosidase inhibitors by screening libraries based on N- [4-(benzyloxy) benzoyl] alanine derivatives

A library of 72 compounds related to N- [4-(benzyloxy) benzoyl]alanine (I) was synthesized, prepared and screened for alpha-glucosidase inhibitory activity. Four compounds showed potent inhibition, six compounds moderate inhibition, and 16 were weak inhibitors. One compound, N- [4-(benzyloxy) benzoyl] serine, was found to be a potent inhibitor of alpha-glucosidase with 100% inhibition at 1 micro M. This inhibitor was at least five times more potent than the lead compound I.     

Exceptionally Persistent Nitrogen-Centered Free Radicals. Syntheses, ESR Spectra, Isolation, and X-ray Crystallographic Structures of N-(Arylthio)-2-tert-butyl-4,6-diarylphenylaminyl and N-(Arylthio)-4-tert-butyl-2,6-diarylphenylaminyl Radicals(1)

The preparation, ESR spectra, isolation, and X-ray crystallographic structure of N-(arylthio)-2-tert-butyl-4,6-diarylphenylaminyls (1) and N-(arylthio)-4-tert-butyl-2,6-diarylphenylaminyls (2) are described. The aminyls are generated by PbO(2) oxidation of N-(arylthio)-2-tert-butyl-4,6-diarylanilines and N-(arylthio)-4-tert-butyl-2,6-diarylanilines. The kinetic ESR study shows that the aminyls are quite persistent, even in the presence of oxygen, and exist in the individual radical forms. Among the seventeen aminyls prepared, N-[(4-nitrophenyl)thio]-2-tert-butyl-4,6-diphenylphenylaminyl (1b), N-[(4-nitrophenyl)thio]-2-tert-butyl-4,6-bis(4-chlorophenyl)phenylaminyl (1f), N-[(4-nitrophenyl)thio]-4-tert-butyl-2,6-diphenylphenylaminyl (2b), N-[(4-nitrophenyl)thio]-4-tert-butyl-2,6-bis(4-chlorophenyl)phenylaminyl (2h), and N-[(3,5-dichlorophenyl)thio]-4-tert-butyl-2,6-bis(4-chlorophenyl)phenylaminyl (2j) are isolated as radical crystals. The crystallographic structures of 1b and 2b are determined by the X-ray crystallographic analyses. Aminyls 1 and 2 give similar ESR spectra consisting of 1:1:1 triplets with the a(N) values of 0.921-0.948 mT. Deuteration of the phenyl groups on the anilino benzene ring gives rise to a further splitting of the nitrogen 1:1:1 triplet by the anilino meta (0.126-0.138) and phenylthiyl ortho and para protons (0.077-0.096 mT). Upon recording at high gain, one of the partly deuterated aminyls gives satellite lines due to (33)S isotopes at natural abundance from which a(33)(S) is determined to be 0.51 mT. The ESR parameters for 1 and 2 are compared with those for structurally close N-(arylthio)-2,4,6-triarylphenylaminyl and N-(arylthio)-2,4,6-tri-tert-butylphenylaminyl.     

2-{2-[3-(取代苯基)-3-氧代-2-1,2,4-三唑-1-基-丙基]-苯基}-2-甲氧亚氨基乙酸甲酯和乙酰甲胺类衍生物的合成与杀菌活性研究

以2-甲基苯甲酰甲酸甲酯为起始原料, 通过与甲氧基胺的盐酸盐、甲胺、N-溴代丁二酰亚胺(NBS)和1H-1,2,4-三氮唑钠反应合成了两个系列共计22个2-{2-[3-(取代苯基)-3-氧代-2-1,2,4-三唑-1-基-丙基]-苯基}-2-甲氧亚氨基乙酸甲酯和乙酰甲胺类的衍生物. 经IR, 1H NMR和MS对目标化合物进行了结构表征. 用浓度为 10 µg•mL－1的目标化合物进行了初步离体杀菌活性试验, 结果表明: Ha4, Ha5, Ha7对油菜菌核病有杀菌活性; Ha2, Hb8对小麦纹枯病有杀菌活性; Hb4对蔬菜灰霉病有杀菌活性; Hb4, Hb5对小麦赤霉病和小麦纹枯病均有杀菌活性.     

直接竞争酶联免疫吸附分析法测定氰戊菊酯

采用活性酯法,将氰戊菊酯半抗原N-[2-(4-氯苯基)-3-甲基丁酰基]-4-氨基丁酸与载体蛋白共价偶联合成突出氰戊菊酯分子结构特征的人工抗原和包被原.以人工抗原免疫新西兰白兔制备抗血清,采用(NH4)2SO4分步盐析和DEAE纤维素柱层析法从抗血清中分离纯化对氰戊菊酯具特异性亲和力的抗体,采用活性酯法,以辣根过氧化物酶标记半抗原N-[2-(4-氯苯基)-3-甲基丁酰基]-6-氨基己酸.采用固定抗体、氰戊菊酯和酶标半抗原直接竞争结合固相抗体的模式, 建立对氰戊菊酯具高特异性的酶联免疫吸附分析方法.在优化条件下, 测定氰戊菊酯标样检测的线性浓度范围为0.001～10.0 mg/L; 检出限0.001 mg/L; 相对标准偏差(RSD, n=5)为9.19%.小白菜中分别添加0.10和5.0 mg/kg氰戊菊酯,直接竞争酶联免疫吸附分析法(ELISA)测定,重复6次,回收率分别为83.8%～109%和93.6%～110%; RSD分别为11.7%和7.25%.对实际样品的有效检出限为0.007 mg/L.其它常用拟除虫菊酯类杀虫剂(氯氰菊酯、溴氰菊脂、功夫菊酯、醚菊酯、联苯菊酯)不干扰氰戊菊酯的测定.