38556-93-3Relevant articles and documents
Anti-inflammatory, ulcerogenic and platelet activation evaluation of novel 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids
Felipe, Josyelen L.,Cassamale, Tatiana B.,Louren?o, Leticia D.,Carvalho, Diego B.,das Neves, Amarith R.,Duarte, Rita C.F.,Carvalho, Maria G.,Toffoli-Kadri, Monica C.,Baroni, Adriano C.M.
, (2021/12/27)
This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs 8–13 (L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non– ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids 8–13 (L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.
Design, click conventional and microwave syntheses, DNA binding, docking and anticancer studies of benzotriazole-1,2,3-triazole molecular hybrids with different pharmacophores
Alharbi, Khalid,Ali, Imran,Aljuhani, Ateyatallah,Alraqa, Shaya Yahya,Aouad, Mohamed Reda,Rezki, Nadjet
, (2020/09/11)
Despite the availability of some drugs, there is an urgent need for effective anti-cancer medication. It is due to various side effects and non-functionality of the present drugs; especially at the late stage of cancer. Therefore, three series (4a-e, 6a-e and 8a-j; 21 compounds) of benzotriazole-1,2,3-triazole hybrids (carrying different pharmacophores) have been designed and synthesized (by both conventional and microwave syntheses) through the Cu(I)-catalyzed click 1,3-dipolar cycloaddition reaction of the propargylated benzotriazole with the appropriate aliphatic, aromatic and phenyl/benzyl acetamide azides. The syntheses times were from 6 to 12 h and 4 to 8 min in conventional and microwave syntheses. The yields were 80 to 86percent and 89 to 95percent in conventional and microwave syntheses; confirming microwave synthesis as an economic and eco-friendly method. These compounds were characterized by proper spectroscopic methods. The anticancer activities with A549 and H1299 lung cancer cell lines were in the range of 70.0 to 90.0percent for 4a-e series, 78.0 to 90.0percent for 6a-e series and 81.0 to 90.0percent for 8a-j series. The reported compounds showed good DNA binding constants in the range of 1.3 × 103 to 11.90 × 105 M?1. The docking results suggested strong DNA bindings of the reported compounds in the minor grooves of DNA; through hydrogen bonding and hydrophobic interactions. The quite good anticancer activities and high DNA binding constants have indicated that the reported molecules may be future anticancer agents.
Cycloaddition Reactions of Azides and Electron-Deficient Alkenes in Deep Eutectic Solvents: Pyrazolines, Aziridines and Other Surprises
Casarrubios, Luis,Díez-González, Silvia,Lachhani, Kushal,Pimpasri, Chaleena,Rzepa, Henry S.,Sebest, Filip,White, Andrew J. P.
supporting information, (2020/05/19)
The reaction of organic azides and electron-deficient alkenes was investigated in a deep eutectic solvents. A series of highly substituted 2-pyrazolines was successfully isolated and their formation rationalised by DFT calculations. The critical effect of substitution was also explored; even relatively small changes in the cycloaddition partners led to completely different reaction outcomes and triazolines, triazoles or enaminones can be formed as major products depending on the alkene employed. (Figure presented.).
Metal-Free Synthesis of Functional 1-Substituted-1,2,3-Triazoles from Ethenesulfonyl Fluoride and Organic Azides
Giel, Marie-Claire,Smedley, Christopher J.,Mackie, Emily R. R.,Guo, Taijie,Dong, Jiajia,Soares da Costa, Tatiana P.,Moses, John E.
supporting information, p. 1181 - 1186 (2019/12/11)
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.
Methyl-2,2-difluoro-2-(fluorosulfonyl) acetate (MDFA)/copper (I) iodide mediated and tetrabutylammonium iodide promoted trifluoromethylation of 1-aryl-4-iodo-1,2,3-triazoles
Arunachalam, Pirama Nayagam,Chandran, Thirumurugan Kothandarama,Corte, James R.,Gupta, Anuradha,Kumar, Hemantha,Mathur, Arvind,Nimje, Roshan Y.,Panja, Chiradeep,Puttaramu, Jayashankara Vaderapura
supporting information, (2020/06/08)
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.
Nucleophilic Iron Complexes in Proton-Transfer Catalysis: An Iron-Catalyzed Dimroth Cyclocondensation
Baykal, Aslihan,Zhang, Dihan,Knelles, Jakob,Alt, Isabel T.,Plietker, Bernd
supporting information, p. 3003 - 3010 (2019/08/21)
The nucleophilic iron complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) is an active catalyst in C?H-amination but also in proton-transfer catalysis. Herein, we describe the successful use of this complex as a proton-transfer catalyst in the cyclocondensation reaction between azides and ketones to the corresponding 1,2,3-triazoles. Cross-experiments indicate that the proton-transfer catalysis is significantly faster than the nitrene-transfer catalysis, which would lead to the C?H amination product. An example of a successful sequential Dimroth triazole–indoline synthesis to the corresponding triazole-substituted indolines is presented.
Thermal azide-Alkene cycloaddition reactions: straightforward multi-gram access to Δ2-1,2,3-Triazolines in deep eutectic solvents
Sebest, Filip,Casarrubios, Luis,Rzepa, Henry S.,White, Andrew J. P.,Díez-González, Silvia
supporting information, p. 4023 - 4035 (2018/09/11)
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.
Design, synthesis and anticancer biological evaluation of novel 1,4-diaryl-1,2,3-triazole retinoid analogues of tamibarotene (AM80)
Aleixo, Mariana A. A.,Garcia, Taís M.,Carvalho, Diego B.,Viana, Luiz H.,Amaral, Marcos S.,Kassab, Najla M.,Cunha, Marilin C.,Pereira, Indiara C.,Guerrero, Palimécio G,Perdomo, Renata T.,Matos, Maria F. C.,Baroni, Adriano C. M.
, p. 109 - 124 (2017/12/08)
We report herein the design and synthesis via click chemistry of twelve novel triazole retinoid analogues of tamibarotene (AM80) and the evaluation of their anticancer activities against six cancer cell lines: HL60, K562, 786, HT29, MCF7 and PC3. Among the synthesized compounds, two were more potent than tamibarotene against solid tumor cells, and one of them had similar potency to tamibarotene against HL60 cells. The bioisosteric exchange between the amide group and the 1,2,3-triazole core in the retinoid agent tamibarotene (AM80) reported in this work is a valid strategy for the generation of useful compounds against cancer.
Transient Protection of Organic Azides from Click Reactions with Alkynes by Phosphazide Formation
Meguro, Tomohiro,Yoshida, Suguru,Igawa, Kazunobu,Tomooka, Katsuhiko,Hosoya, Takamitsu
supporting information, p. 4126 - 4130 (2018/07/15)
A method for protecting organic azides from click reactions with alkynes is reported. Treatment of azides with Amphos affords phosphazides, which are stable under click reaction conditions and are easily converted back to azides by treatment with elemental sulfur. Thus, the method allows for facile modification of azide compounds via site-selective click reactions.
Smectic liquid crystals comprising triazole banana shaped achiral molecules: Synthesis and characterization
Li, Xiaolian,Zhang, Zongying,Liuya
, p. 395 - 404 (2017/05/26)
A series of novel liquid crystals containing [1,2,3]-triazole ring were synthesized via “click chemistry.” Their mesomorphic properties and photoelectric properties were investigated and the results indicated that most of compounds exhibited SmA over a wide temperature range (about 50°C). The threshold voltage and the response time of the mixture, T4 and LC 50100 were shorten 0.43?V and 71.5?ms with respect to those of LC 50100 respectively.
