Synthesis and bioactivities of novel 2-(thioether/sulfone)-5-pyrazolyl-1,3,4-oxadiazole derivatives

By introducing the pyrazole moiety into the 5-position of 1,3,4-oxadiazole,a series of novel 2-(thioether/sulfone)-5-pyrazolyl-l,3,4-oxadiazole derivatives were synthesized.Preliminary bioassays suggested that target compounds exhibited appreciable activity against pathogenic bacteria Xanthomonas oryzae pv.oryzae(Xoo) and five phytopathogenic fungi in vitro.Among them,the half-maximal effective concentration(EC_(50)) values of 6c,7a,7b and 7c against Xoo were within 16.6 μg/mL and 65.7 μg/mL,which were better than those of commercial agricultural antibacterial bismerthiazol(92.6 μg/mL) and thiodiazole copper(121.8 μg/mL).While compounds 7a,7b,and 7c exerted comprehensive antifungal activity toward five plant fungi,which were comparable with that of hymexazol.The results demonstrated that this kind of compounds can be further studied and developed as promising antifungal and antibacterial agents.     

Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents

A series of novel triazole derivatives containing γ-lactam were designed and synthesized, and their structures were confirmed by ~1H NMR,~(13)CNMR and HRMS. The in vitro antifungal activities of the target compounds were evaluated. The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition,the docking model for 2A and CYP51 was investigated.     

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.     

Design,synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

A series of sulfenimine cephalosporin sulfoxide derivatives(7a–v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C b-lactamase cephalosporinase compared with the tazobactam. The most promising compounds 7c and 7n(IC50= 7.6 and8.6 mmol/L, respectively) were further investigated in combination with cefradine against a variety of clinical isolated b-lactamase-producing bacterial strains.     

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma(HCT116),prostate adenocarcinoma(PC-3) and liver carcinoma(HepG-2) using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship(SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data(MS,IR,~1H NMR and ~(13)C NMR) and elemental analysis.     

Syntheses,Spectral Studies and Bioanalyses of Some Triorganotin（IV） Complexes of Cephlaxine

Five novel triorganotin（IV） complexes have been synthesized by refluxing trimethyl, triethyl, tributyl, triphenyl and tribenzyltin chloride with Cephlaxine. These compounds were characterized by spectroscopic （IR, IH, 13C, 119Sn NMR） techniques and elemental analysis. The results obtained through these techniques are in full agreement with the proposed 1：1 stoichiometry. The synthesized compounds were than tested against various microorganisms and fungi. The results of new products obtained showed that the triphenyltin（IV） complex displayed promising activity against all types of bacteria and fungi used while all other compounds showed significant antibacterial and antifungal activity.     

Synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of new series of benzothiazole derivatives

New series of benzothiazole derivatives were designed and synthesized. The newly synthesized compounds were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. Compounds 6j and 6o showed the highest activity against E. coli and S. aureus. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus fumigatus293. Compounds 4c, 4g and 6j exhibited the highest activity against C. albicans. In addition, compounds4 a and 6j displayed promising activity against A. fumigatus 293. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds4 a, 6j and 6p showed moderate activity. The in vitro cytotoxicity testing of the synthesized compounds was performed against cervical cancer(Hela) and kidney fibroblast cancer(COS-7) cell lines. Results indicated that all tested compounds have IC50 values 50 mmol/L against both cell lines. Molecular properties, toxicities, drug-likeness, and drug score profiles of compounds 4a–c, 5a, 6g,h, 6j, 6l, 6o and7 c,d were also assessed.     

Synthesis and bioactivities of some new 1H-pyrazole derivatives containing an aryl sulfonate moiety

A new series of 1H-pyrazole derivatives 5a-j bearing an aryl sulfonate moiety have been synthesized by a one-pot cyclo-condensation reaction of 2-(3-(dimethylamino)acryloyl)phenyl-4-methyl benzene sulfonates 4a-e and hydrazine hydrate or phenyl hydrazine in ethanol under reflux conditions.Some of the newly synthesized compounds were screened for their anti-inflammatory activity.All synthesized compounds were screened against Gram positive and Gram negative bacterial and fungal strains.The compound 5b was found to be a potent anti-inflammatory agent while the majority of the compounds were found to be active against microbial strains.     

Synthesis of 6,8-dichloroquinolones utilizing new method and evaluation of their antibacterial activities

Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride,which was obtained from the starting material of tetrachlorophthalic anhydride.Their in vitro antibacterial activities were evaluated.As a result of this study,compounds 21c and 21d were twofold more potent than ciprofloxacin (CPFX) and norfloxacin (NFLX) against Staphylococcus aureus-9,and with the same potent as CPFX and NFLX while against Escherichia coli-2,but were less potent than references in against Pseudomonas aeruginosa-17.     

Synthesis and Antitumor Activity of Tanshinone Analogues

8, 8-Dimethyl-5, 6, 7,8-tetrahydrophenanthrene-3, 4-dione (3) and 8, 8-dimethyl-2- ( 1-hydroxy ethyl) -5,6, 7, 8-tetrahydrophenanthrene-3,4-dione (4), two analogues of the antitumor active tanshinone, were synthesized from anisole. The synthesized compounds 3 and 4 were shown to be highly active against leukemia P-388 cell fine as assayed by in vitro MTT method.     

Synthesis of new 1,2,4-triazole[3,4-b][1,3,4]thiadiazoles bearing pyrazole as potent antimicrobial agents

A new series of 6-(aryl/heteryl)-3-(5-methyl-1-phenyl-1H-4-pyrazolyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (7a-j) has been synthesized by the reaction of 4-amino-5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-4H-1,2,4-triazol-3-yl-hydrosulfide (6) with POCl(3) and the corresponding aryl/heteryl carboxylic acid, in ethanol at reflux temperature for 12 h. All the synthesized compounds were tested for in vitro activities against certain strains of bacteria such as Staphylococcus aureus, Bacillus subtilis, Escherichia coli and fungi such as Aspergillus niger, Aspergillus nodulans, Alternaria alternate. Compounds having 4-chlorophenyl (7d), 4-aminophenyl (7f), 4-nitrophenyl (7h) and 3-pyridyl (7i) substituents at 6-position of thiadiazole ring, showed marked inhibition of bacterial and fungal growth nearly equal to the standards. The other new compounds also showed appreciable activity against the test bacteria and fungi.     

3-（CH2）nCO2C2H5-1,5-苯并硫氮杂的合成、晶体结构及抑真菌活性

为了寻找具有更高抗真菌活性的杂类化合物并对高活性的杂衍生物A进行构效关系研究,设计合成了38个3-(CH2)nCO2C2H5-1,5-苯并硫氮杂衍生物6和7(n=1,2),其结构经核磁共振波谱、质谱、红外光谱及元素分析等确证;并采用X射线单晶衍射技术测定了目标化合物的立体结构,发现其分子中的七元杂环是扭曲的船式构象.实验还考察了合成化合物的抑真菌活性,结果表明,当乙氧羰基烷基[(CH2)nCO2C2H5]在七元杂环的3位时杂的活性降低;将Lewis CeCl3.7H2O-NaI用于催化含硫化合物与α,β-不饱和酮的迈克尔加成反应,发现该催化剂能有效促进高位阻α,β-不饱和酮与邻氨基苯硫酚的迈克尔加成;同时研究了中间体5的分子内缩合反应,发现TiCl4是合成Schiff碱非常有效的促进剂.     

Synthesis and antimicrobial study of linked heterocyclics containing Pyrazole-pyrimidine-thiazolidin-4-one

A new series of linked heterocyclics, 3-[4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinyl]-2-(aryl/heteryl)-1,3-thiazolan-4-ones (6a-j), has been synthesized by the one-pot cyclo-condensation of 4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinamine (5), aryl/heteroaryl aldehyde and thioglycolic acid. The structures of the synthesized compounds have been confirmed via IR, (1)H-NMR, (13)C-NMR, MS and elemental analyses. Further, all the newly synthesized compounds 6a-j have been assayed for their antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi. The compounds containing moieties like 4-nitrophenyl (6c), 3-nitrophenyl (6d), 4-dimethylaminophenyl (6g), 2-furyl (6i) and 1,3-benzodioxole (6j), at 2-position of thiazolidin-4-one ring exhibited good inhibitory activity against all the tested organisms.     

Synthesis and Antimicrobial Activity of Novel Thiazole Substituted Pyrazole Derivatives

A series of new 1‐[4‐(2,3,4‐substituted‐phenyl) thiazol‐2‐yl]‐3‐(2,3,4‐substituted‐phenyl)‐1H‐pyrazole‐4‐carbaldehyde ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m ), 4‐[4‐(4‐substituted‐phenyl) thiazol‐2‐yl]‐3‐(4‐substituted‐phenyl)‐1‐phenyl‐1H‐pyrazole ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i ), 4‐[4‐(4‐substituted phenyl)thiazol‐2‐yl]‐1‐phenyl‐1H‐pyrazol‐3‐amine ( 10a , 10b , 10c , 10d , 10e , 10f , 10g ) have been synthesized by using Vilsmeier Haack formylation and Hantzsch reaction in high yield. All the synthesized compounds were tested qualitative (Zone of inhibition) and quantitative antimicrobial activities (MIC). Most of the synthesized compounds showed potent antimicrobial activity against gram positive and gram negative bacteria as well as fungi species.     

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.     

3-杂环硫亚甲基头孢菌素衍生物的半合成及抗菌活性研究

通过取代噁二唑硫酮、噻二唑硫酮及三唑硫酮分别和头孢菌素母体7-ACA反应,制得14种7-氨基-3-杂环硫亚甲基头孢菌素新母体2a-2n,用1-芳基-5-甲基-1H-1,2,3-三唑-4-甲酰氯与头孢菌素新母体缩合,制得2种新的7β-(1-芳基-5-甲基-1H-1,2,3-三唑-4-甲酰胺基)-3-(2-取代1,3,4-bI二唑-5-硫亚甲基)头孢菌素4c,4d.新化合物结构经元素分析、IR、¹HNMR及FAB-MS确认.初步体外抗菌结果表明,新母体化合物2对革兰氏阳性菌有抑制活性且在相同浓度下比7-ACA强20倍,而头孢菌素4c,4d对革兰氏阳性和阴性菌都有显著抑制活性.     

Synthesis and Antimicrobial Activity of 1,3,4‐Oxadiazole‐2(3H)‐thione and Azidomethanone Derivatives Based on Quinoline‐4‐carbohydrazide Derivatives

A new series compounds of quinoline derivatives were synthesized by reaction of 3‐(carboxymethyl)‐2‐arylquinoline‐4‐carboxylic acids 1a , 1b , 1c with different nucleophiles. The structures of the new compounds were elucidated on the basis of FTIR, ¹H‐NMR, ¹³C‐NMR spectral data, GC/MS, and chemical analysis. Investigation of antimicrobial activity of all new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration count against four pathogenic bacteria and two pathogenic fungi. Most of the new compounds were significantly active against bacteria and fungi.     

Thromboxane A2 receptor antagonists. III. Synthesis and pharmacological activity of 6,6-dimethylbicyclo[3.1.1]heptane derivatives with a substituted sulfonylamino group at C-2

Four stereoisomers of the title compounds based on side chain ring junctions, (+)-7a, (+)-7b, (-)-7c and (-)-24, were synthesized from (-)-myrtenol and (+)-nopinone. The (1R,2R,3S,5S)-isomer (+)-7b had the most potent inhibitory activity against platelet aggregation and did not show partial agonist activity (shape change of platelets). We also synthesized the antipode, (-)-7b, and derivatives of (+)-7b with various kinds of substituents at the sulfonylamino group, 34a-n and p. The one-carbon homologated compound, (+)-58, was also prepared. The inhibitory activities of these compounds against platelet aggregation were measured.     

Synthesis and antimicrobial evaluation of some pyrazole derivatives

Reaction of a series of (E)-3-phenyl-4-(p-substituted phenyl)-3-buten-2-ones with p-sulfamylphenyl hydrazine in glacial acetic acid gave the corresponding hydrazones, subsequent treatment of which with 30% HCl afforded pyrazole-1-sulphonamides. On the other hand, refluxing of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide in ethanol containing a few drops of acetic acid gave pyrazoline-1-thiocarboxamides and isonicotinoyl pyrazolines, respectively. The structures of the synthesized compounds were determined on the basis of their elemental analyses and spectroscopic data. The antimicrobial activity of the newly isolated heterocyclic compounds was evaluated against Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed a moderate degree of potent antimicrobial activity.