173601-46-2Relevant academic research and scientific papers
A Simple Efficient Click Synthesis of Novel Crown Ethers Containing 1,2,3-Triazole Moieties
Elamari,Ouerghui,Ammari,Girard
, p. 1785 - 1790 (2019)
Novel crown ether derivative containing 1,4-disubstituted-1,2,3-triazole moieties were synthesized. At the first step of the synthesis 4,13-diaza-18-crown-6 and 4-aminobenzo-15-crown-5 were converted into terminal alkynes, which were then subjected to copper(I)-catalyzed alkyne-azide coupling (CuAAC) in methylene chloride. This coupling reaction was performed according to the concept of click chemistry, using an Amberlyst A-21-supported copper(I) iodide catalyst.
1,5-Disubstituted 1,2,3-Triazoles as Amide Bond Isosteres Yield Novel Tumor-Targeting Minigastrin Analogs
Grob, Nathalie M.,Schibli, Roger,Béhé, Martin,Valverde, Ibai E.,Mindt, Thomas L.
, p. 585 - 592 (2021/04/12)
1,5-Disubstituted 1,2,3-triazoles (1,5-Tz) are considered bioisosteres of cis-amide bonds. However, their use for enhancing the pharmacological properties of peptides or proteins is not yet well established. Aiming to illustrate their utility, we chose the peptide conjugate [Nle15]MG11 (DOTA-dGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) as a model compound since it is known that the cholecystokinin-2 receptor (CCK2R) is able to accommodate turn conformations. Analogs of [Nle15]MG11 incorporating 1,5-Tz in the backbone were synthesized and radiolabeled with lutetium-177, and their pharmacological properties (cell internalization, receptor binding affinity and specificity, plasma stability, and biodistribution) were evaluated and compared with [Nle15]MG11 as well as their previously reported analogs bearing 1,4-disubstituted 1,2,3-triazoles. Our investigations led to the discovery of novel triazole-modified analogs of [Nle15]MG11 with nanomolar CCK2R-binding affinity and 2-fold increased tumor uptake. This study illustrates that substitution of amides by 1,5-disubstituted 1,2,3-triazoles is an effective strategy to enhance the pharmacological properties of biologically active peptides.
Halomethyl-triazoles for rapid, site-selective protein modification
Brewster, Richard C.,Hulme, Alison N.
, (2021/09/20)
Post-translational modifications (PTMs) are used by organisms to control protein structure and function after protein translation, but their study is complicated and their roles are not often well understood as PTMs are difficult to introduce onto proteins selectively. Designing reagents that are both good mimics of PTMs, but also only modify select amino acid residues in proteins is challenging. Frequently, both a chemical warhead and linker are used, creating a product that is a misrepresentation of the natural modification. We have previously shown that biotin-chloromethyl-triazole is an effective reagent for cysteine modification to give S-Lys derivatives where the triazole is a good mimic of natural lysine acylation. Here, we demonstrate both how the reactivity of the alkylating reagents can be increased and how the range of triazole PTM mimics can be expanded. These new iodomethyl-triazole reagents are able to modify a cysteine residue on a histone protein with excellent selectivity in 30 min to give PTM mimics of acylated lysine side-chains. Studies on the more complicated, folded protein SCP-2L showed promising reactivity, but also suggested the halomethyl-triazoles are potent alkylators of methionine residues.
Reactions of α-haloacroleins with azides: Highly regioselective synthesis of formyl triazoles
Zhang, Dongsheng,Fan, Yingzhu,Yan, Zhongliang,Nie, Yi,Xiong, Xingquan,Gao, Lizhu
supporting information, p. 4211 - 4216 (2019/08/07)
A general metal-free route to 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles was developed. α-Haloacroleins reacted with organic azides in a DMSO/H2O mixture solvent at room temperature to produce 1,4-disubstituted triazoles (up to 99%) with exclusive regioselectivities. This protocol is convenient and scalable with a broad substrate scope including aliphatic and aromatic azides. The resulting triazoles exhibited an aldehyde group at the C4 position and demonstrated synthetic utilizations. One 1,2,3-triazole compound containing diastereotopic protons was also identified.
Synthesis and Antimicrobial Evaluation of (1-(2-(Benzyloxy)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl Benzoate Analogues
Kaushik,Pahwa, Ashima,Kumar, Devinder,Kumar, Ashwani,Singh, Dharmendra,Kumar, Krishan,Luxmi, Raj
, p. 1720 - 1728 (2018/07/25)
A convenient one pot synthesis of 20 (1-(2-(benzyloxy)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl benzoate analogues (5a–5t) with ester functionality was carried out via Cu(I) catalyzed click reaction between prop-2-yn-1-yl benzoates and benzyl 2-azidoacetates. The structure of synthesized triazoles were explicated by various spectral techniques like FT-IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry and evaluated for in vitro antimicrobial potential against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Candida albicans, and Aspergillus niger. Most of synthesized triazole derivatives exhibited average to excellent activity against tested microbial strains.
Click synthesis of some mono/bis 1,2,3-triazoles with ester linkage and their microbicidal activity
Kaushik,Pahwa, Ashima
, p. 2171 - 2176 (2017/10/06)
Synthesis of some new 1,4-disubstituted 1,2,3-triazoles with ester functionality is reported employing Cu(I) catalyzed Huisgen [3+2] cycloaddition reaction of prop-2-yn-1-yl benzoates with 1,4-phenylenebis(methylene) bis(2-azidoacetate) and benzyl 2-azidoacetates. The synthesized compounds were well characterized through FTIR, 1H NMR, 13C NMR and HRMS. Further, the synthesized triazole derivatives were accessed for in vitro antimicrobial activity against one Gram-positive bacterial strain Staphylococcus aureus, three Gram-negative bacterial strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes and two fungi Candida albicans and Aspergillus niger. Few of the synthesized disubstituted 1,2,3-triazoles displayed moderate to good inhibitory activity against tested microbial strains.
Modulating lectin inhibition with N-glycosyl-1,2,3-triazole scaffolds
Azcune, Itxaso,Balentova, Eva,Sagartzazu-Aizpurua, Maialen,Ignacio Santos,Miranda, Jose I.,Fratila, Raluca M.,Aizpurua, Jesus M.
, p. 2434 - 2444 (2013/05/23)
The synthesis of three families of sialyl LewisX (sLe X) mimetics based on triazole and bis-triazole scaffolds is reported. The flexibility of these mimetics is dictated by the scaffold and gradually increases from flexible to rigid.
Synthesis and in vitro evaluation of potential anticancer activity of mono- and bis-1,2,3-triazole derivatives of bis-alkynes
Elamari, Hichem,Slimi, Riadh,Chabot, Guy G.,Quentin, Lionel,Scherman, Daniel,Girard, Christian
supporting information, p. 360 - 364 (2013/03/29)
In order to find new molecules with cytotoxic activity against cancer cells, we prepared bis-akyne amides derived from propiolic acid. The bis-alkynes were then transformed in their mono-1,2,3-triazole analogs onto the amide side, due to its greater reactivity, using a catalyst-free Huisgen's reaction. The mono-triazoles were then subjected to the copper (I)-catalyzed version of the previous reaction (CuAAC), using a supported catalyst, to produce bis-triazoles. All products were obtained pure after simple trituration or filtration procedures. All synthetic compounds were tested in vitro for their cytotoxic activity using B16 melanoma cells. Four compounds (7, 23, 25 and 33) showed activities in the micromolar range (21 μM) whereas three compounds (3, 22 and 38) presented activity at low micromolar concentrations (10 μM), and two analogs (2 and 13) were active at nanomolar levels (1 μM).
"click" synthesis of nonsymmetrical bis(1,2,3-triazoles)
Aizpurua, Jesus M.,Azcune, Itxaso,Fratila, Raluca M.,Balentova, Eva,Sagartzazu-Aizpurua, Malaien,Miranda, Jose I.
supporting information; experimental part, p. 1584 - 1587 (2010/06/16)
Chemical Fig. Repretation Unsymmetrically 1,1'-disubstituted 4,4'-bis-1 H-1,2,3-triazoles 4 have been prepared from 4-ethynyl-1,2,3-triazoles 5 and azides. Following a "double-click" strategy, two complementary approaches were implemented for the preparation of the key 4-ethynyltriazole Intermediates 5: (a) the stepwise Swern oxidatlon/Ohira-Bestman alkynylation of readily available 4-hydroxymethyl-1,2,3-triazoles 8 and (b) the stepwise cycloaddition of TMS-1,4-butadiyne 9. The method is highlighted by Its compatibility with orthogonally protected and functlonallzed saccharide-peptide hybrids and its ability to be extended to the trlsubstituted counterparts 12.
Design, synthesis and evaluation of potent thymidylate synthase X inhibitors
Esra Oenen,Boum, Yap,Jacquement, Claire,Spanedda, Maria Vittoria,Jaber, Nada,Scherman, Daniel,Myllykallio, Hannu,Herscovici, Jean
body text, p. 3628 - 3631 (2009/04/06)
Three synthesized series of compounds based on a thiazolidine core allowed identification of potent inhibitors of thymidylate synthase X. The evaluation of the catalytic activity of the enzyme in the presence of these molecules revealed two distinct classes of compounds that inhibit ThyX with submicromolar concentrations, which could lead, after optimization, to effective inhibitors with potential biomedical interest.
