Design and Synthesis of 1-Glycosyl-4-{N-[(2'-morpholinethoxy)-phenyl]aminomethyl}-1H-1,2,3-triazoles as Calcium Activators

A series of novel 1-glycosyl-4-{N-[(2'-morpholinethoxy)phenyl]aminomethyl}-1H-1,2,3-triazoles was designed and synthesized through a simple and efficient multistep synthetic method in good yields. The 1,2,3-triazole moiety acted as a single disubstituted ring and a linker between carbohydrates(D-glucose, D-galactose, maltose and lactose) and morpholine. The compounds were characterized by ¹H NMR, ¹³C NMR and mass spectra(MS). Two different deprotection methods were discussed. The effects of compounds 5a, 5c and 6e on the intracellular calcium ion concentration([Ca²⁺]_i) in the central neurons of S. exigua were well investigated by calcium imaging technique. The results demonstrated that compound 6e could elevate the calcium concentration in the glial cells, not in the neurons.     

Syntheses and Biological Activities of Novel 3-Bromo-1-（3-chloropy- ridin-2-yl）-N-hydroxy-N-aryl- 1H-pyrazole-5-carboxamides

A series of novel 3-bromo-1-（3-chloropyridin-2-yl）-N-hydroxy-N-aryl-lH-pyrazole-5-carboxamides was synthesized by the reaction of pyrazole carbonyl chloride with each of substituted phenylhydroxyamines. The latter ones were prepared in good yields by reducing substituted nitrobenzene compounds with Zn/NH4CI reductant system in alcohol. Structures of the title compounds were determined by IR, 1H NMR, and HRMS. Their insecticidal and fungicidal activities were evaluated by larvicidal test against oriental armyworm and the mycelium growth rate method, respectively.     

对称吡啶基二噻吩乙烯光致变色化合物的合成与性能

二噻吩乙烯光致变色化合物具有热稳定性高、抗疲劳性好等优点。 本文以2-甲基噻吩为原料,经过Suzuki偶联、傅克酰基化、McMurry环合3步反应制备1,2-二(5-吡啶基-2-甲基噻吩-3-基)环戊烯,总收率61%。 所有中间体及目标产物均已通过核磁共振、质谱、红外光谱等技术手段表征。 该合成方法具有合成步骤少、简便、总收率高、易于工业化生产等优点。 利用紫外-可见吸收光谱、荧光光谱对该化合物及其与镍离子、锡离子相互作用的光致变色性能以及应用进行了研究。 对称吡啶基二噻吩乙烯通过与金属配位在紫外光的照射前后显示出不同的颜色和光谱吸收,可以用作新型金属离子探针。     

Design,Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing Tetrahydrophthalimide Substructure

To develop novel sulfonylurea herbicides, a series of chlorsulfuron derivatives was designed and synthesized through introducing tetrahydrophthalimide substructure taken from protoporphyrinogen IX oxidase(PPO) inhibitors onto the critical 5-position of the classical benzene ring. The structures of title compounds were confirmed by infrared spectroscopy, ultraviolet spectroscopy, ¹H and ¹³C NMR spectrometry, mass spectrometry and elemental analysis. In addition, the crystal structure of compound II-5 was further determined by X-ray diffraction analysis. Bioassay results showed that individual compounds exhibited good herbicidal activities, especially compound II-8, which displayed 100% inhibition rate against Echinochloa crusgalli at 150 g/ha(1 ha=10⁴ m²) with the method of foliage spray in the pot experiment.     

Synthesis and Antifungal Activities of Novel Strobilurin Derivatives Containing Quinolin-2(1H)-one Moiety

To discover novel lead compounds with better antifungal activities, a series of novel strobilurin derivatives containing quinolin-2(1H)-one moiety was designed and synthesized via intermediate derivatization method. Their structures were characterized by means of ¹H nuclear magnetic resonance(¹H NMR), ¹³C NMR and high resolution mass spectrometry(HRMS). The biological assay results indicate that most target compounds exhibit good to excellent fungicidal activities against 10 plant pathogens. Compounds 4d, 5b and 5c possess 94.1%, 83.8% and 80.9% in vitro inhibition respectively against Rhizotonia cereals at the concentration of 50 μg/mL, which are better than that of the control agents. Especially, the inhibition activities of compound 4d against all of the tested fungi approach or exceed those of the controls. The structure-activity relationship was also discussed.     

四氢咪唑并[2',1':2,3]噻吩并[5,4-c]哌啶衍生物的合成及抗肿瘤活性

以4-哌啶酮为原料,经过胺基保护、缩合、环合、脱保护等步骤,设计合成了一系列新型的5,6,7,8-四氢咪唑并[2',1':2-3]噻吩并[5,4-c]哌啶类化合物。通过核磁共振波谱仪(~1H NMR、~(13)C NMR)、质谱(MS)和元素分析确证了其结构。对其体外活性研究发现,该类化合物对乳腺癌细胞MCF-7具有一定的抑制活性,其中化合物5a的抑制活性最为显著,半数抑制浓度(IC_(50))值达到了8.6μmol/L。为此类化合物的抗肿瘤活性研究提供了参考。     

Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives

A series of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives were designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000 mg/L. Compound 6q presented the best activity against Digitaria sanguinalis (L) Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50 mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.     

Synthesis and insecticidal evaluation of tetrahydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A series of novel tetrahydroimidazo[1,2-a]pyridine-5(1H)-one derivatives containing a electronegative pharmacophore(=CNO₂) were synthesized via practical aza-ene reaction and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Preliminary bioassays showed that some of the target compounds exhibited good insecticidal activity against brown planthopper(Nilaparvata lugens) and cowpea aphids(Aphis craccivora) at 500 mg L^-1. Among them, compound 11h was active against brown planthopper at 100 mg L^-1. The insecticidal activities varied significantly depending on the types and patterns of the substituents, which provided guidance for further investigation on structure modifications.     

Synthesis and Herbicidal Activities of Novel Uracil Derivatives Containing Pyrimidinyl Moiety

In order to find novel protoporphyrinogen oxidase inhibitors with high efficacy, broad-spectrum activity, and safety to crops, nine title compounds（4a-4i） were designed and synthesized by introducing pyrimidine moiety into the uracil skeleton with commercially herbicide butafenacil as the lead compound. Their structures were con- firmed by 1H NMR, IR, mass spectroscopy and elemental analysis. The bioassay results indicate that most of com- pounds 4 tested exhibit good to excellent herbicidal activities against B. campestris, A. retroflexus, E. crusgalli and D. sanguinalis in pre-emergence treatment at a dose of 1.5 kg/ha（1 ha=10^4 m^2）, for example, compound 4i showed 100% inhibition against the four plants tested in pre-emergence treatment at a dose of 1.5 kg/ha. So, this type of skeleton can be used as a valuable lead compound for the further development of a pre-emergent herbicide.     

Improved Antiproliferative Activities of a New Series of 1,3,4-Thiadiazole Derivatives Against Human Leukemia and Breast Cancer Cell Lines

Twenty-two novel 1,3,4-thiadiazole derivatives were synthesized using different aromatic acids as starting materials, followed by cyclization, coupling and deprotection reaction. The structures of all the target compounds were identified by means of ¹H nuclear magnetic resonance(NMR), ¹³C NMR and high resolution mass spectrometer(HRMS). Further biological evaluations were performed for chronic myelogenous leukemia cell and breast cancer cell. The results suggest that most of the target compounds exhibit potent anti-proliferative activities. Especially, compound 5b shows better antiproliferative activities against MDA-MB-231 and K562 cell lines compared with gossypol.     

Design,Synthesis and Insecticidal Activities of Novel 5-Alkoxyfuran-2(5H)-one Derivatives

A series of novel 5?alkoxyfuran-2(5H)-one derivatives was synthesized, and characterized by 1H NMR, 13C NMR and HRMS. Biological activities of all the title compounds were evaluated systematically. Preliminary bioassays indicated that most of the compounds exhibited moderate insecticidal activities against Aphis craccivora and Nilaparvata lugens at 100 mg/L. Compounds 4h and 4w exhibited 100% mortality rate against Aphis craccivora at 100 mg/L, and compound 4h exhibited good mortality rate against Aphis craccivora and Nilaparvata lugens (60% and 75%, respectively) even at 4 mg/L. The results demonstrated the impact of various chemical groups on insecticidal activities and provided a potential clue for further exploring novel high-effective broad-spectrum insecticides.     

新型瑞香酮类似物的合成及杀菌活性

以瑞香狼毒中分离的天然产物(E)-1,5-二苯基-2-烯-1-戊酮(A)为先导, 引入色酮片段设计合成了15个新型的瑞香酮类似物, 其结构均经IR, ¹H NMR, ¹³C NMR及元素分析或HRMS确证. 杀菌活性测试结果表明, 在100 mg/mL浓度下, 部分化合物的杀菌活性优于先导化合物A, 其中化合物6d对水稻纹枯病菌和黄瓜灰霉病菌的抑制率分别为87%和86%, 与对照药剂苯醚甲环唑相当, 值得进一步优化研究.     

Synthesis,structural characterization and solubility of 2-(1-substituted-1,11-undecylidene)-5-arylimino-△~3 -1,3,4-thiadiazolines

A series of novel 2-(1-substituted-1,11-undecylidene)-5-arylimino-△~3-1,3,4-thiadiazolines(4) were synthesized and their structure was characterized by ~1H NMR,~(13)C NMR and elemental analysis.Their solubility in both polar and non-polar solvents is significantly improved owing to the introduction of ethyl or methylthio group at cyclododecyl ring as compared with parent compounds[1,2-(1,11-undecylidene)-5-arylimino-△~3-1,3,4-miadiazolines].However,their fungicidal activity against Rhizoctonia solani is ...     

Synthesis and Anticoagulant Bioactivity Evaluation of 1, 2, 5-Trisubstituted Benzimidazole Fluorinated Derivatives

Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by molecular docking. Five compounds which obtained high scores were selected to synthesize. All the target products were char-acterized by ¹H NMR, ¹³C NMR and high resolution mass spectra(HRMS) and preliminarily screened for inhibitory activity against thrombin, among which three compounds(5a, 5c and 5e) were evaluated in vitro. The results showed that compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demonstrated that these compounds may act as candidates for further studies on thrombin inhibitors.     

Synthesis and fungicidal activity study of novel daphneolone analogs with 2,6-dimethylmorpholine

A series of novel daphneolone analogs was designed and synthesized on the basis of natural product 1,5-diphenyl-2-penten-1-one(I) from Stellera chamaejasme L. as lead compound, whereby 2,6-dimethylmorpholine moiety was introduced to replace 1-phenyl group. Their structures were confirmed by IR,1H NMR, and HRMS(ESI) or elemental analysis,13 C NMR for some representative compounds. The two isomers of target compounds were separated and identified by NOESY technique and chemical method.All of the synthesized compounds have been evaluated for anti-plant pathogenic fungi activities. The results showed that some compounds exhibited moderate to good antifungal activities against tested fungi at the concentration of 50 mg/L. Among them, compound 7d, with a 4-bromine-substituted phenyl group and cis-2,6-dimethylmorpholine moiety, displayed best activity with an EC50 of 23.87 mmol/L against Valsa mali, superior to lead compound I. In addition, preliminary structure–activity relationship analysis indicated that, between two isomers of target compounds, the antifungal activities of the isomer with cis-2,6-dimethylmorpholine were better than the trans-isomer.     

3-取代-3-苯基-1-茚酮类化合物的合成

以3-苯基-1-茚酮（1）为原料,THF为溶剂,二异丙基氨基锂（LDA）为碱,与碘代烷（RI）经亲核取代反应合成了4个3-取代-3-苯基-1-茚酮类化合物（3a~3d),其中3b~3d为新化合物,其结构经¹H NMR, ¹³C NMR 和EI-GC-MS表征。在最佳反应条件［1 1.0 eq., LDA/RI=2.1/1.5（当量比）,于0 ℃~rt反应5 h］下,3a~3d收率为70％～80％。     

Synthesis and biological activity of fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines

In our lead finding program, 12 new fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines were prepared via a practical three-step procedure starting from (iso)nicotinic hydrazides. The fluorine substituted aryl fragment was introduced in the last step through cyclocondensation of N-(3-pyridyl-1,2,4-triazol-5-yl)guanidines and fluoro/trifluoromethyl substituted benzaldehydes. The structures of the compounds were confirmed by ¹H and ¹³C NMR spectral data. The tautomeric preferences for the compounds were established using 2D NOESY experiments. The antiproliferative activity of the synthesized 1,2,4-triazolo[1,5-a][1,3,5]triazines was evaluated against breast, colon and lung cancer cell lines. The highest antiproliferative activity in the series was found for 2-(pyridine-3-yl)-7-(4-trifluoromethylphenyl)-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amine. The lack of inhibitory activity against bovine dihydrofolate reductase (DHFR) indicated that the antiproliferative activity was realized via other mechanisms.     

1,3,2-Diazastanna-[3]ferrocenophanes bearing alkyn-1-yl groups at tin and their 1,1-organoboration with triethylborane—molecular structure of a novel spirotin compound

2,2-Dichloro-1,3-bis(trimethylsilyl)-1,3,2-diazastanna-[3]ferrocenophane (3) reacts with lithium alkynides LiCCR¹ to give the corresponding di(alkyn-1-yl)tin derivatives 4a (R¹=^tBu) and 4b (R¹=SiMe₃). 1,1-Organoboration of 4 with triethylborane affords the spirotin compounds 5 which contain both a ferrocenophane and a stannacyclopentadiene ring. The crystal structure of 5b was determined by X-ray analysis. The compounds 4 and 5 were characterised in solution by multinuclear magnetic resonance (¹H-, ¹¹B-, ¹³C-, ¹⁵N-, ²⁹Si-, ¹¹⁹Sn-NMR), using pulsed field gradients in HMBC experiments for the ¹H detected ¹⁵N- and ¹¹⁹Sn-NMR signals. The compound 5b was also studied by solid-state ¹³C, ²⁹Si and ¹¹⁹Sn MAS NMR in order to correlate liquid and solid-state NMR data with the structural evidence.     

Synthesis and Biological Evaluation of Novel Anthranilic Diamides Containing N-H/CH3-1H-Pyrazole

In order to systematically study the structure-activity relationship of anthranilic diamides and develop insecticides with simple structure and high efficiency, a series of novel anthranilic diamides containing N-H/CH₃-1H-pyrazole was designed and synthesized. Their chemical structures were characterized by ¹H NMR spectra, high resolution mass spectrometry(HRMS) or ¹³C NMR spectra. The preliminary bioassay results indicated that all title compounds displayed moderate insecticidal activity against oriental armyworm(Mythimna separata) at 200 mg/L and fungicidal activities against six kinds of fungi at 50 mg/L, especially compound 5i showed 50% insecticidal activity at 25 mg/L. In addition, some compounds exhibited certain antitumor activities. It was demonstrated that the introduction of CH₃ group into pyrazole ring was superior to H for the insecticidal activity.     

Discovery of ErbB/HDAC inhibitors by combining the core pharmacophores of HDAC inhibitor vorinostat and kinase inhibitors vandetanib,BMS-690514, neratinib,and TAK-285

By combining the core pharmacophores of HDAC inhibitor vorinostat and kinase inhibitors vandetanib, BMS-690514, neratinib, and TAK-285 with 1,2,3-triazole as linker, eight novel 6-substituted-4- aminoquinazolin derivatives were synthesized and characterized by ¹H NMR, ¹³C NMR, and high resolution mass spectrometry. Their inhibitory activities against five enzymes (VEGFR2, HER2, EGFR, HDAC1, and HDAC6) and five cancer cell lines (A549, BT-474, A431, SK-BR-3, and NCI-H1975) were evaluated. The bioassay results show that the introduction of triazole linked vorinostat-like segment dramatically changed the selectivity profiles of newly synthetic compounds relative to vandetanib, BMS- 690514, neratinib, and TAK-285. Among them, compound 6b exerted outstanding enzymatic and cellular activities through its simultaneous and synergistic inhibitions on multiple pathways, which might have the great potential to confer the better benefits than single-targeted inhibitors in cancer therapy.