26330-06-3Relevant articles and documents
Regioselective reduction of 1h-1,2,3-triazole diesters
Butler, Christopher R.,Bendesky, Justin,Schoffstall, Allen Milton
, (2021/09/24)
Regioselective reactions can play pivotal roles in synthetic organic chemistry. The reduction of several 1-substituted 1,2,3-triazole 4,5-diesters by sodium borohydride has been found to be regioselective, with the C(5) ester groups being more reactive towards reduction than the C(4) ester groups. The amount of sodium borohydride and reaction time required for reduction varied greatly depending on the N(1)-substituent. The presence of a β-hydroxyl group on the N(1)-substituent was seen to have a rate enhancing effect on the reduction of the C(5) ester group. The regioselective reduction was attributed to the lower electron densities of the C(5) and the C(5) ester carbonyl carbon of the 1,2,3-triazole, which were further lowered in cases involving intramolecular hydrogen bonding.
On-Nanoparticle Gating Units Render an Ordinary Catalyst Substrate- And Site-Selective
Kim, Minju,Dygas, Miroslaw,Sobolev, Yaroslav I.,Beker, Wiktor,Zhuang, Qiang,Klucznik, Tomasz,Ahumada, Guillermo,Ahumada, Juan Carlos,Grzybowski, Bartosz A.
supporting information, p. 1807 - 1815 (2021/02/05)
When an organometallic catalyst is tethered onto a nanoparticle and is embedded in a monolayer of longer ligands terminated in "gating"end-groups, these groups can control the access and orientation of the incoming substrates. In this way, a nonspecific catalyst can become enzyme-like: it can select only certain substrates from substrate mixtures and, quite remarkably, can also preorganize these substrates such that only some of their otherwise equivalent sites react. For a simple, copper-based click reaction catalyst and for gating ligands terminated in charged groups, both substrate- and site-selectivities are on the order of 100, which is all the more notable given the relative simplicity of the on-particle monolayers compared to the intricacy of enzymes' active sites. The strategy of self-assembling macromolecular, on-nanoparticle environments to enhance selectivities of "ordinary"catalysts presented here is extendable to other types of catalysts and gating based on electrostatics, hydrophobicity, and chirality, or the combinations of these effects. Rational design of such systems should be guided by theoretical models we also describe.
Regioselective synthesis of 4-fluoro-1,5-disubstituted-1,2,3-triazoles from synthetic surrogates of α-fluoroalkynes
Jana, Sampad,Adhikari, Sweta,Cox, Michael R.,Roy, Sudeshna
supporting information, p. 1871 - 1874 (2020/02/20)
α-Fluoroalkynes are elusive molecules due to their instability and inaccessibility. Here, we show that α-fluoronitroalkenes can serve as synthetic surrogates of α-fluoroalkynes in [3+2] cycloaddition reactions with organic azides facilitated by a catalytic amount of trifluoroacetic acid (TFA). This work provides the first regioselective method to access 4-fluoro-1,5-disubstituted-1,2,3-triazoles.
Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model
Jia, Yan,Si, Lihui,Lin, Ruixin,Jin, Hongjuan,Jian, Wenwen,Yu, Qing,Yang, Shuli
, p. 62 - 70 (2019/04/04)
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.
Synthesis, characterization, and antimycobacterial activity of novel thymol-triazole hybrids
Negi, Beena,Rawat, Diwan S
, p. 113 - 124 (2018/09/14)
Thymol is a naturally occurring phenolic compound showing various biological activities. A library of novel thymol-triazole hybrids was synthesized and evaluated for their inhibitory activity against Mycobacterium tuberculosis (M.tb), the causative agent of TB. Most of the compounds were found to be active against M.tb H37Rv at 50 μg/mL concentration. These identified compounds have promise to be further optimized into more potent inhibitors against M.tb.
Structure–Activity Relationships of Antiplasmodial Pantothenamide Analogues Reveal a New Way by Which Triazoles Mimic Amide Bonds
Guan, Jinming,Tjhin, Erick T.,Howieson, Vanessa M.,Kittikool, Tanakorn,Spry, Christina,Saliba, Kevin J.,Auclair, Karine
, p. 2677 - 2683 (2018/12/11)
Pantothenamides are potent growth inhibitors of the malaria parasite Plasmodium falciparum. Their clinical use is, however, hindered due to the ubiquitous presence of pantetheinases in human serum, which rapidly degrade pantothenamides into pantothenate and the corresponding amine. We previously reported that replacement of the labile amide bond with a triazole ring not only imparts stability toward pantetheinases, but also improves activity against P. falciparum. A small library of new triazole derivatives was synthesized, and their use in establishing structure–activity relationships relevant to antiplasmodial activity of this family of compounds is discussed herein. Overall it was observed that 1,4-substitution on the triazole ring and use of an unbranched, one-carbon linker between the pantoyl group and the triazole are optimal for inhibition of intraerythrocytic P. falciparum growth. Our results imply that the triazole ring may mimic the amide bond with an orientation different from what was previously suggested for this amide bioisostere.
Selective C(sp2)-H Halogenation of "click" 4-Aryl-1,2,3-triazoles
Goitia, Asier,Gómez-Bengoa, Enrique,Correa, Arkaitz
supporting information, p. 962 - 965 (2017/02/26)
Selective bromination reactions of "click compounds" are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C-H ortho-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C-H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of "click compounds". The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal.
Synthesis and antiproliferative activity of new 1,2,3-triazole/flavone hybrid heterocycles against human cancer cell lines
Sowjanya,Jayaprakash Rao,Murthy
, p. 1864 - 1871 (2017/09/25)
A series of new 1,2,3-triazole/flavone hybrid heterocycles were synthesized from 6-amino flavone via key intermediate N-propargyl flavone 6 by adopting the Sharpless Click reaction. Copper(I) catalyzed 1,3-dipolar cycloaddition reaction that gave products in high yields. All the synthesized compounds were screened for their in vitro antiproliferative activity against four human cancer cell lines, HeLa (cervical cancer cell line), MIA PaCa (pancreatic cancer cell line), MDA-MB-231 (breast cancer cell line), and IMR 32 (neuroblastoma cancer cell line). Compounds 7a, 7b, 7d, 7g (GI50 = 0.01–0.68 μM) demonstrated promising antiproliferative activity.
Triazole substitution of a labile amide bond stabilizes pantothenamides and improves their antiplasmodial potency
Howieson, Vanessa M.,Tran, Elisa,Hoegl, Annabelle,Fam, Han Ling,Fu, Jonathan,Sivonen, Kate,Li, Xiao Xuan,Auclair, Karine,Saliba, Kevin J.
, p. 7146 - 7152 (2016/11/28)
The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo. In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC50s) of ～50 nM, and three others have submicromolar IC50s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [14C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.
Synthesis of α-santonin derived acetyl santonous acid triazole derivatives and their bioevaluation for T and B-cell proliferation
Dangroo, Nisar A.,Singh, Jasvinder,Dar, Alamgir A.,Gupta, Nidhi,Chinthakindi, Praveen K.,Kaul, Anpurna,Khuroo, Mohmmed A.,Sangwan, Payare L.
, p. 160 - 169 (2016/05/24)
A new series of α-santonin derived acetyl santonous acid 1,2,3-triazole derivatives were synthesised using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their in vitro inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among the synthesised series, compounds 2-10 and 19 exhibited significant inhibition against ConA and LPS stimulated T-cell and B-cell proliferation in a dose dependent manner. More significantly compounds 4, 9-10 and 19 exhibited potent inhibition activity with remarkably lower cytotoxicity on the mitogen-induced T cell and B cell proliferation at 1 μM concentration. The compound 6 displayed potent immunosuppressive effects with ～89% against LPS induced B-cell and ～83% against ConA stimulated T-cell proliferation at 100 μM concentration without cytotoxicity. Compound 10 was more selective against B cell proliferation and exhibited 81% and 69% suppression at 100 and 1 μM concentration respectively. The present study led to the identification of several santonin analogs with reduced cytotoxicity and strong inhibition activity against the cell proliferation induced by the mitogens.
