2101-88-4

An environmental friendly heterogeneous catalyst Cell-CuI-NPs was employed for the synthesis of biologically promising 1-((1-aryl)-1H-1,2,3-triazol-4-yl)methyl-5-fluoroindoline-2,3-diones via CuAAC click reaction of 5-fluoro-(1-prop-2-ynyl)indoline-2,3-di

In this work, 40 analogs with a natural maslinic acid core (from Olea europaea L.) and various aromatic azides were synthesized. A regiospecific, facile and practical synthesis of 1,5-triazolyl derivatives by Ru(II)-catalyzed azide-alkyne cycloaddition (R

Azides and acetylenes are bio-orthogonal functional groups that can be readily coupled using copper(I)- or ruthenium(II)- catalyzed 1,3-dipolar cycloaddition reactions. Using non-fluorescent aromatic azides and aromatic acetylenes, covering a range of electron rich and poor building blocks, the Huisgen cycloaddition afford 1,4-disubstituted or 1,5-disubstituted 1,2,3-triazoles. Using a combinatorial approach by running reaction in parallel in polypropylene 96-well plates we discovered several new fluorescent 1,2,3-triazoles scaffolds. These compounds show diverse interactions with biomolecules that could find applications in biology in, for example, fluorescence microscopy or biomolecule quantification.

The invention relates to triazole [5, 4-d] pyrimidone tricyclic compounds as well as a preparation method and application thereof.The triazole [5, 4-d] pyrimidone tricyclic compounds are prepared by following steps: taking different substituted anilines a

Luminescent supramolecular hydrogels have shown extensive potential for a variety of applications due to their unique optical properties and biocompatibility. Coordination self-assembly provides a promising strategy for the preparation of supramolecular h

This report describes the synthesis of a carbon nanotube-bound dendrimer and three carbon nanotube-bound monometallic complexes and their use as catalysts. The polyamidoamine third generation dendrimer used here incorporates pyrazole-triazole moieties suitable for ligating iridium(III) centres. The monometallic complexes use the same pyrazole-triazole ligands coordinated to an iridium(III) centre. All catalysts were characterized using ICP-AES and XPS to evaluate their metal loadings on the carbon surface with significantly higher relative weight percentage of iridium determined for the denrimeric species. The catalytic activity and practicality of the formed catalysts were tested using two different intramolecular hydroamination reactions.

Background: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action. Methods: Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 mM for 24 h. The 50% effective drug concentration (EC50) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC50) determined using CellTiter-Glo solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain. Results: Compounds 3 ((E)-4-methyl-N'-(2-(4(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylen ebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC50 of 16 and 21 mM and CC50 of 285 and 2,593 mM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5. Conclusions: Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.

We developed a regiodivergent syntheses of 4- and 5-bromo-substituted 1,2,3-triazoles in copper-catalyzed azide-alkyne cycloadditions (CuAACs) by taking advantage of bromo(phosphoryl)ethyne 1 as a bromoethyne equivalent. A one-shot dephosphorylative CuAAC

The cost-effective TPPH2/TBACl-catalyzed (TPPH2=dianion of tetraphenyl porphyrin; TBACl=tetrabutyl ammonium chloride) carbon dioxide cycloaddition to N-aryl aziridines was successful in synthesizing N-aryl oxazolidin-2-ones. A cataly

Two series of new compounds containing 1,2,3-triazole moiety were designed as putative GlyT1 inhibitors aiming the discovery of new hits with activity in cognitive disorders. 1,4-Disubstituted α-hydroxy-1,2,3-triazoles were obtained as racemates in moderate to good yields by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction (click chemistry) as the key step between propargyl alcohols and aryl azides, previously prepared from anilines or boronic acids. Benzo[c]chromene-triazoles were planned to be obtained by palladium-catalyzed C?H activation using [bis(trifluoroacetoxy)iodobenzene] (PhI(TFA)2) of some α-hydroxy-1,2,3-triazoles, since benzo[c]chromenes are also privileged groups with several biological activities, including to the central nervous system. Unexpectedly, 9H-fluorenes-1,2,3-triazoles, instead of benzo[c]chromenetriazoles, were obtained by Friedel-Crafts alkylation reaction. The two series of compounds were tested for inhibition of the glycine transporter (rat GlyT1 isoform) but only the α-hydroxy-1,2,3-triazole 9b was active (half maximal inhibitory concentration (IC50) = 8.0 μM).

A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 μM), which was higher than harringtonine (IC50 = 10.55 μM), pemetrexed (IC50 = 3.39 μM), and rucaparib (IC50 = 4.91 μM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.

The boom in growth of 1,4-disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the CuI-catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click-inspired protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1-substituted-1,2,3-triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts.

Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.

While several methods are available for the synthesis of a host of trifluoromethylated heterocycles, very few of them have been applied to access 4-trifluoromethylated 1,2,3-triazoles. We report herein a general methodology for the trifluoromethylation of 1-aryl-4-iodo-1, 2, 3-triazoles. Tetrabutylammonium iodide (TBAI) has been shown to provide enhanced conversion in these CuI-mediated reaction using methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA). The method exhibited broad functional group tolerance and was applied to the synthesis of a library of 1-aryl-4-trifluoromethyl-1,2,3-triazoles on the multi-gram scale.

A series of 1,3,4-trisubstituted-1,2,3-triazolium iodide salts (4a–c) were synthesized via a three-step reaction sequence. Corresponding anilines (1a–c) were converted to azides (2a–c) which were then treated with phenylacetylene with “Click” chemistry to access 1,4-disubstituted-1,2,3-triazoles (3a–c). Subsequent methylation of 1,4-disubstituted-1,2,3-triazoles (3a–c) yielded 1,3,4-trisubstituted-1,2,3-triazoliumiodide salts (4a–c) in appreciable yields. All the synthesized compounds were characterized by 1H and 13C NMR, ATR–IR spectroscopic techniques and elemental analyses. Additionally, the structure of 1-(4-chlorophenyl)-4-phenyl-1,2,3-triazole (3b) was confirmed by single crystal X-ray diffraction analysis. The catalytic activity of 4a–c in a catalytic system consisting of 1,3,4-trisubstituted-1,2,3-triazoliumiodide salt/palladium(II) acetate/base were investigated toward Suzuki–Miyaura and Heck–Mizoroki cross-coupling reactions. The Suzuki–Miyaura cross-coupling reactions were carried out under mild reaction conditions with good to excellent yields, whereas Heck–Mizoroki cross-coupling reactions were performed at elevated temperature with moderate yields. Further, in situ method skips the synthetic procedure of preparing the palladium(II) complexes and hence is more economical and less tedious. (Figure presented.).

Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.

In the current study, a new series of 1,2,3-triazole derivatives was synthesized via copper (I) catalyzed azide-alkyne cycloaddition reaction using a series of synthesised p-substituted phenyl azides and propiolic acid. In addition, a new series of hetero

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4-oxadiazole, and 1,2,3-triazole linked through a thioether bridge was achieved by one-pot synthesis by exploring multicomponent Cu-catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC-Mass. The X-ray analysis of 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8a) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8b) demonstrated more potent antibacterial activity against Gram-negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2-(((1-(2,4-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(1-(4 isobutylphenyl)ethyl)-1,3,4-oxadiazole (8e) exhibited anticancer activity with IC50 of 27.50 and 31.03?μg/mL against HeLa and MCF-7 cell lines, respectively.

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.

A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an ICsub

In this present work, a series of new 1-(substituted-phenyl)-1H-1,2,3-triazolyl-4-carboxylic acid derivatives was synthesized via copper (I) catalyzed azide-alkyne cycloaddition reaction. Since these synthesized 1,2,3-triazole compounds containing a carbo

In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 μM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 μM caused a significant (P 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and ?9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer.

A synthetic strategy with the visible-light photo-catalytic synergistic combination of electron and energy transfer processes has been developed. The mild reaction conditions allow the radical-radical cross-coupling phenomenon for the multicomponent synthesis of β-arylsulfonyl(diarylphosphinoyl)-α,α-diarylethyl-amines from readily available arylsulfinic acids (diarylphosphine oxides), 1,1-diarylethylenes and arylazides.

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.

Amyloid beta (Aβ) peptide aggregation is considered as one of the key hallmarks of Alzheimer's disease (AD). Moreover, Aβ peptide aggregation increases considerably in the presence of metal ions and triggers the generation of reactive oxygen species (ROS)

A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a–u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited s

A series of novel (E)-2-[(1-phenyl-1H-1,2,3-triazol-4-yl)methylene]-2,3-dihydro-1H-inden-1-one derivatives has been synthesized by condensation of 1-phenyl-1H-1,2,3-triazole-4-carbaldehydes with 2,3-dihydro-1H-inden-1-one. The synthesized compounds are ch

A series of novel 1,4-substituted bis-aralkyl and aryl 1,2,3-triazoles bearing thiophene chalcones are synthesized via the Claisen condensation of bis propargyl acetophenone intermediate with thiophene-2-carboxaldehyde followed by the Huisgen cycloaddition of the accumulated bis propargyl chalcone intermediate with various aryl and aralkyl azides. Structures of the synthesized compounds are characterized by IR, NMR and mass spectroscopy. The products are tested for antimicrobial and antioxidant activities, and some of those exhibit antibacterial and antifungal activity. The moderate to poor DPPH free radical scavenging activity is determined for some products.

An efficient and simple protocol for the synthesis of aryl azides by the coupling of aryl iodides with sodium azide, in good to excellent yields in DMSO at 95°C under catalysis by Cu(OAc)2·H2O and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), has been established. The optimised loadings of Cu(OAc)2·H2O and DBU were 10 mol% and 15 mol% respectively.

This work deals the synthesis of aryl azides catalyzed by heterogeneous copper (II) complex of 3,5–bis (2–benzothiazolyl) pyridine, [Cu (II)(BTP)(OTf)2], immobilized on chloromethylated polystyrene, [Cu (II)(BTP)(OTf)2]@CMP. The prepared catalyst was characterized by different analytical techniques such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), field emission scanning electron microscopy (SEM), energy dispersive X–ray spectroscopy (EDX), elemental analysis, and FT-IR and UV–Vis spectroscopic methods. This catalytic system showed excellent activity in the synthesis of aryl azides by the reaction of aryl halides with sodium azide in the presence of catalytic amounts of [Cu (II)(BTP)(OTf)2]@CMP. Moreover, this unique catalyst could be recovered easily and reused several times without any considerable loss of its catalytic activity.

The multi-gram synthesis of a wide range of 1,2,3-Triazolines via azide-Alkene cycloaddition reactions in a Deep Eutectic Solvent (DES) is reported. The role of DES in this transformation as well as the origin of the full product distribution was studied with an experimental/computational-DFT approach.

The invention belongs to the field of chemical medicine, particularly relates to a micromolecule capable of resisting malignant tumor, acute leukemia and arthritis, multiple sclerosis and immunological rejection and a preparation and application of the mi

In an attempt to find potential neuroprotective agents, a series of novel 3-(1-((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl) methoxyimino) ethyl)-2H-chromen-2-one derivatives 6a–j were synthesized by using “click reaction” and evaluated for their in vit

[Figure not available: see fulltext.] New 1-aryl-4-(β-D-fructopyranos-3-O-yl)methyl-1H-1,2,3-triazole derivatives have been synthesized by a CuAAC reaction and their antibacterial and antifungal activity has been evaluated. Some of the derivatives showed

Microenvironment-sensitive fluorescent nucleosides present attractive advantages over single-emitting dyes for sensing inter-biomolecular interactions involving DNA. Herein, we report the rational design and synthesis of triazolyl push-pull fluorophore-la

The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hel

An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/ heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO3 in water had been developed. The amount of NaHSO3 had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO3 was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO3 was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.

The invention discloses a synthesis method for an aryl azide compound. The synthesis method includes the steps of: adding an iodo-aryl compound, sodium azide, 1,8-diazabicyclo[5.4.0]undecane-7-ene and a catalyst into a reaction container filled with a solvent, performing a stirring reaction to the reaction mixture at 60-105 DEG C with TLC tracing detection until the reaction is completed, adding ammonia water to the reaction mixture, extracting the reaction mixture for 3 times by ethyl acetate, washing the reaction mixture for 1 time by saturated salt water, drying an organic phase, performing suction filtration and spinning solvent removal, and performing column chromatographic purification to obtain a target product. The method employs easy-to-obtained raw materials and has wide selection range of copper source of the catalyst, has mild reaction condition, simple operation and high yield.

A highly efficient catalytic system, CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea, for the copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC) was discovered. In the above catalytic system, substituted thiourea acts both as a reductant and a ligand. CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea is both an economical and efficient catalyst for the CuAAC reaction. In addition, the new catalytic system has advantageous features including mild and green reaction conditions, and broad substrate compatibility. A variety of 1,4-disubstituted 1,2,3-triazoles have been prepared with good to excellent yields with the CuSO4·5H2O/1-(4-methoxyphenyl)-3-phenylthiourea catalytic system in aqueous solution.

Herein we report a two-step sequence for the preparation of amides starting from azides and enolisable aldehydes. The reaction proceeded via the formation of triazoline intermediates that were converted into amides via Lewis acid catalysis. Preliminary st

Diosgenin, a promising anticancer steroidal sapogenin, was isolated from Dioscorea deltoidea. Keeping its stereochemistry rich architecture intact, a scheme for the synthesis of novel diosgenin analogues was designed using Cu (I)-catalysed alkyne-azide cy

Using a click chemistry approach, a series of gallic-acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethyl esters was synthesized to develop more effective antioxidants. The results of DPPH screening indicate that few of the synthesized analogs display better antioxidant effect compared to the standards. Among all, compounds, 9 and 20 displayed highest DPPH radical scavenging effect with IC50 values as low as 6.4±0.2 and 7.9±0.4 μM respectively, compared to the standard ascorbic acid (IC50=12±0.8 μM) and gallic acid (IC50=9.0±0.6 μM). Compound 10 also displayed a potent antioxidant effect with IC50 of 10.80±0.4 μM. This study provides an important aspect with regard to the use of these gallic-acid based synthetic antioxidants in food industry as dietary supplements.

A combinatorial chemical library of fifty-nine novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile, designed as hybrid molecules of phenazine, pyran, indole and 1,2,3-triazole pharmacophores, were constructed in this study. Cytotoxic evaluation indicated that some compounds exhibited moderate cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compound 36 was found to have best antiproliferative activity against the A549 cancer cell line with IC50 value of 5.4 μM. All compounds had low or no effect against L02 and HUVEC non-cancer cell lines. Compound 36 was further confirmed to mainly locate mitochondria in A549 cancer cells via laser-scanning confocal microscopy. Moreover, compound 36 was proved to increase ROS production and induce cell cycle arrest in S phase. Western blot analysis illustrated Bax/Bcl-2 ratio was increased at dose-dependent manner, and both cleaved caspase-3 and cleaved caspase-9 was enhanced by treated with compound 36. All the above evidences in vitro indicated that compound 36 might induce the apoptosis of A549 cancer cells via a mitochondria-dependent pathway.

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

A quick and efficient method for the reduction of azides to amines in water using d-glucose and KOH as green reagents is reported. The protocol is simple, inexpensive, scalable, and can be applied to different aromatic, heteroaromatic and sulphonyl azides. A high level of chemoselectivity is observed for azide reduction in the presence of other reducible functionalities like cyano, nitro, ether, ketone, amide and acid. The reaction gets completed in a short time (5-20 minutes), and furnishes the amines in high yield (85-99%). Unlike conventional hydrogenations, this reduction protocol does not require any metal catalyst, elaborate experimental setup or use of high-pressure equipment.

A series of ferrocene-1H-1,2,3-triazole hybrids namely 1-(4-nitrophenyl)-4-ferrocenyl-1H-1,2,3-triazole (1), 1-(4,4′-dinitro-2-biphenyl)-4-ferrocenyl-1H-1,2,3-triazole (2), 1-(3-chloro-4-fluorophenyl)-4-ferrocenyl-1H-1,2,3-triazole (3), 1-(4-bromophenyl)-

A transition-metal-free, mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in a sequential one-pot reaction by nitration of iodine(III) reagents with two carbon ligands, which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides, and constitutes an important step towards catalytic reactions with these hypervalent iodine reagents. An efficient nitration of isolated diaryliodonium salts has also been developed, and the mechanism is proposed to proceed by a [2,2] ligand coupling pathway.

In an attempt to arrive at more potent cytotoxic agent than the bioactive natural product betulinic acid, influence of small structural modifications of its 1, 2, 3 triazole derivatives tethered at C-28 and both C3, C-28 using click chemistry approach has been studied. The chemically characterized triazoles have been screened for in vitro cytotoxicity against four human cancer cell lines HL-60, MiaPaCa-2, PC-3 and A549 which has allowed to identify triazole derivative 28{1N (4-fluoro phenyl)-1H-1, 2, 3-triazol-4-yl} methyloxy betulinic ester having better potency profile than the parent compound with IC50 values in the range of 5-7 μM. It caused disruption of mitochondrial membrane potential, rendered Bcl-2 cleavage, Bax translocation and decrease Bcl-2/Bax ratio. These events are accompanied by activation of caspases -9, -3, which cleave the PARP-1. It also induces caspase-8, which is involved in extrinsic apoptotic pathway. Therefore, it induces apoptosis through both intrinsic and extrinsic pathways in human leukemia HL-60 cells.

Fischer's approach towards the synthesis of aryl azides and triazinoles from diazonium salts and hydroxylammonium chloride (phenylhydraxylamine) was reinvestigated and optimized. The new methodology enables the preparation of aryl azides and triazinoles in high yields in water at room temperature. The procedure is very simple, robust, easily scalable, reproducible, and "green".

A convenient CuI/DBU catalyzed one-pot method has been developed for the synthesis of 1,4-disubstituted 1,2,3-triazoles through the coupling of aryl iodides with sodium azide, followed by the intermolecular cyclization between the generated aryl azides and phenylacetaldehyde derivatives or alkynes in DMSO. The established protocol was compatible with a wide scope of substrates in good to excellent yields.

A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro cytotoxic activities against four typical cancer cell lines (A549, H460, HT-29, and MKN-45). Most compounds showed moderate-to-excellent antiproliferative activity. Compounds 32, 36, 37, 45, 51, and 52 were further examined for their inhibitory activity against c-Met kinase. The promising compound 37, with a c-Met IC50 value of 2.27 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The analysis of their structure-activity relationships indicated that compounds with EWGs, especially chloro group, at 2-position on the phenyl ring (moiety B) have potent antitumor activity.