- Discovery of Novel Inhibitors of Uridine Diphosphate- N-Acetylenolpyruvylglucosamine Reductase (MurB) from Pseudomonas aeruginosa, an Opportunistic Infectious Agent Causing Death in Cystic Fibrosis Patients
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Pseudomonas aeruginosa is of major concern for cystic fibrosis patients where this infection can be fatal. With the emergence of drug-resistant strains, there is an urgent need to develop novel antibiotics against P. aeruginosa. MurB is a promising target
- Abell, Chris,Acebrón-García-De-Eulate, Marta,Blundell, Tom L.,Brown, Karen P.,Coyne, Anthony G.,Di Pietro, Ornella,Floto, R. Andres,Hess, Jeannine,Holland, Matthew T. O.,Kim, So Yeon,Marchetti, Chiara,Mayol-Llinàs, Joan,Mendes, Vitor
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p. 2149 - 2173
(2022/02/14)
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- Preparation of Acidic 5-Hydroxy-1,2,3-triazoles via the Cycloaddition of Aryl Azides with β-Ketoesters
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Herein, a high-yielding cycloaddition reaction of β-ketoesters and azides to provide 1,2,3-triazoles is described. The reactions employing 2-unsubstituted β-ketoesters were found to provide 5-methyl-1,2,3-triazoles, whereas 2-alkyl-substituted β-ketoester
- Pacifico, Roberta,Destro, Dario,Gillick-Healy, Malachi W.,Kelly, Brian G.,Adamo, Mauro F. A.
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p. 11354 - 11360
(2021/08/20)
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- DNDI-6148: A Novel Benzoxaborole Preclinical Candidate for the Treatment of Visceral Leishmaniasis
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Visceral leishmaniasis (VL) is a parasitic disease endemic across multiple regions of the world and is fatal if untreated. Current therapies are unsuitable, and there is an urgent need for safe, short-course, and low-cost oral treatments to combat this ne
- Bello, Davide,Braillard, Stéphanie,Caljon, Guy,Carvalho, Sandra,Corpas-Lopez, Victoriano,Freund, Yvonne,Gilbert, Ian H.,Glossop, Paul A.,Jacobs, Robert T.,Lukac, Iva,Maes, Louis,Mowbray, Charles E.,Nare, Bakela,Pandi, Bharathi,Patterson, Stephen,Speake, Jason,Van Den Kerkhof, Magali,Wall, Richard J.,Whitlock, Gavin A.,Wyllie, Susan,Yardley, Vanessa,Zuccotto, Fabio
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supporting information
p. 16159 - 16176
(2021/11/16)
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- Primary discovery of 1-aryl-5-substituted-1H-1,2,3-triazole-4-carboxamides as promising antimicrobial agents
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Three series of novel 1H-1,2,3-triazole-4-carboxamides: 1-aryl-5-alkyl/aryl-1H-1,2,3-triazole-4-carboxamides, 1-aryl-5-amino-1H-1,2,3-triazole-4-carboxamides and 1,2,3-triazolo[1,5-a]quinazoline-3-carboxamides were synthesized via base-mediated click azide reactions. Compounds were evaluated for their antimicrobial activities against primary pathogens: Gram-positive and Gram-negative bacterial strains Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, as well as fungal strain Cryptococcus neoformans var. grubii and Candida albicans. Compounds exhibiting moderate to good activities were selected for SAR analysis. Several 5-methyl-1H-1,2,3-triazole-4-carboxamides 4d, 4l, 4r, showed potent antibacterial effect against S. aureus. On the contrary, 5-amino-1H-1,2,3-triazole-4-carboxamide 8b and [1,2,3]triazolo[1,5-a]quinazoline-3-carboxamide 9a were active against pathogenic yeast C. albicans. Thus, compound 4l under 1 μM demonstrated 50% growth inhibition against S. aureus. At the same concentration, the compound 9a killed approx. 40% of C. albicans cells. In general, these compounds demonstrated selective action and no significant impact on the viability of human keratinocytes of HaCaT line.
- Finiuk, Nataliya,Klyuchivska, Olha,Manko, Nazar,Matiychuk, Vasyl,Obushak, Mykola,Pokhodylo, Nazariy,Stoika, Rostyslav
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- Selective Synthesis of Functionally Substituted 1,2,3-Triazoles
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Abstract: Different conditions were used to achieve selective formation of4.5-disubstituted 1-aryl(hetaryl)-1,2,3-triazoles via cycloaddition of thecorresponding enolates and aryl or hetaryl azides. Optimal conditions were foundfor the bromination of 1-(5
- Golobokova, T. V.,Kizhnyaev, V. N.,Proidakov, A. G.
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p. 446 - 453
(2020/04/27)
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- A simple route towards the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles from primary amines and 1,3-dicarbonyl compounds under metal-free conditions
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An acetic acid-promoted approach that enables the synthesis of 1,4,5-trisubstituted 1,2,3-triazole derivatives has been achieved. This transformation employs readily available primary amines, 1,3-dicarbonyls and tosyl azide as the starting materials via a
- Guo, Ningxin,Liu, Xiufen,Xu, Hongyan,Zhou, Xi,Zhao, Huaiqing
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supporting information
p. 6148 - 6152
(2019/07/03)
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- Method for synthesizing 1,2,3-triazole compound
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The invention discloses a method for synthesizing a 1,2,3-triazole compound. The method comprises the step of performing a reaction on p-toluenesulfonyl azide, an amine compound and a dicarbonyl compound under the condition of an acid as an additive in an
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Paragraph 0070; 0071
(2019/07/31)
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- NOVEL OXABOROLE ANALOGS AND USES THEREOF
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This application describes compounds, compositions, and methods which are useful in treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a parasite.
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Paragraph 0115; 0254
(2018/09/21)
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- Copper-catalyzed convenient synthesis and SAR studies of substituted-1,2,3-triazole as antimicrobial agents
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Background: A novel copper-catalyzed synthesis of substituted-1,2,3-triazole derivatives has been developed and performed by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The reaction is one-pot multicomponent. Objective: We state the advancement and execution of a methodology allowing for the synthesis of some new substituted 1,2,3-triazole analogues with antimicrobial activity. Methods: A series of triazole derivatives was synthesized by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The structures of the synthesized compounds were elucidated and confirmed by1H NMR, IR, MS and elemental analysis. All the synthesized compounds were tested for their antimicrobial activity against a series of strains of Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus and Aspergillus nigar for antifungal activity, respectively. Results and Conclusion: From the antimicrobial data, it was observed that all the newly synthesized compounds showed good to moderate level of antibacterial and antifungal activity.
- Sarkate, Aniket P.,Karnik, Kshipra S.,Wakte, Pravin S.,Sarkate, Ajinkya P.,Izankar, Ashwini V.,Shinde, Devanand B.
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- Discovery of novel pyrrolopyrimidine/pyrazolopyrimidine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors
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Six series of pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives bearing 1,2,3-triazole moiety were designed and synthesized, and some bio-evaluation was also carried out. As a result, four points can be summarized: Firstly, some of compounds exhibited excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μm level. In particular, the most promising compound 16d showed equal activity to lead compound foretinib against A549, HepG2, and MCF-7 cell lines, with the IC50 values of 4.79?±?0.82, 2.03?±?0.39, and 2.90?±?0.43?μm, respectively. Secondly, the SARs and docking studies indicated that the in vitro antitumor activity of pyrrolo[2,3-d]pyrimidine derivatives bearing 1,2,3-triazole moiety was superior to the pyrazolo[3,4-d]pyrimidine derivatives bearing 1,2,3-triazole moiety. Thirdly, three selected compounds (16d, 18d, and 20d) were further evaluated for inhibitory activity against the c-Met kinase, and the 16d could inhibit the c-Met kinase selectively by experiments of enzyme-based selectivity. What is more, 16d could induce apoptosis of HepG2 cells and inhibitor the cell cycle of HepG2 on G2/M phase by acridine orange staining and cell cycle experiments, respectively.
- Wang, Linxiao,Liu, Xiaobo,Duan, Yongli,Li, Xiaojing,Zhao, Bingbing,Wang, Caolin,Xiao, Zhen,Zheng, Pengwu,Tang, Qidong,Zhu, Wufu
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p. 1301 - 1314
(2018/05/14)
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- Triazabicyclodecene as an Organocatalyst for the Regiospecific Synthesis of 1,4,5-Trisubstituted N-Vinyl-1,2,3-triazoles
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Herein we report on the 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyzed enolate-mediated regiospecific synthesis of 1,4,5-trisubstituted N-vinyl-1,2,3-triazoles from simple activated carbonyl compounds and N-vinyl azides through [3+2] cycloaddition; u
- Ramachary, Dhevalapally B.,Gujral, Jagjeet,Peraka, Swamy,Reddy, G. Surendra
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supporting information
p. 459 - 464
(2017/02/05)
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- Cycloadduct formation of α,β-unsaturated esters with azides catalyzed by NHC systems
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NHC-catalyzed cycloadduct formation of α,β-unsaturated esters with azides has been developed. This strategy could generate 1,2,3-triazoles and dihydropyrazoles with high yields and regioselectivities in the presence of an N-heterocyclic carbene catalyst.
- Yuan, Huijun,Gao, Hua,Liu, Kun,Liu, Zhantao,Wang, Jian,Li, Wenjun
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supporting information
p. 9066 - 9070
(2017/11/14)
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- Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors
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A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50value of 1.68?nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X?=?CF3, R1?=?F, R2?=?4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.
- Tang, Qidong,Wang, Linxiao,Tu, Yayi,Zhu, Wufu,Luo, Rong,Tu, Qidong,Wang, Ping,Wu, Chunjiang,Gong, Ping,Zheng, Pengwu
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p. 1680 - 1684
(2016/07/27)
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- Discovery and biological evaluation of novel 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety as c-Met kinase inhibitors
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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 biological activities against c-Met kinase and five typical cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG). Most compounds showed moderate to excellent antiproliferative activity. In this study, a promising compound 34, with a c-Met IC50 value of 1.04 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The SAR analyses indicated that compounds with halogen group, especially fluoro group, at 4-position on the phenyl ring (moiety B) have potent antitumor activity, and methylation on the 5-atom linker played an important role in the c-Met enzymatic activity.
- Zhou, Shunguang,Liao, Huimin,Liu, Mingmei,Feng, Guobing,Fu, Baolin,Li, Ruijuan,Cheng, Maosheng,Zhao, Yanfang,Gong, Ping
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p. 6438 - 6452
(2015/02/02)
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- Novel synthesis of 1,4,5-trisubstituted 1,2,3-triazoles via a one-pot three-component reaction of boronic acids, azide, and active methylene ketones
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A series of 1-aryl-5-trifluoromethyl (or difluoromethyl)-1,4,5- trisubstituted 1,2,3-triazoles were synthesized in high yield by a novel one-pot three-component reaction of arylboronic acids, sodium azide, and active methylene ketones, such as ethyl 4,4-difluoroacetoacetate or ethyl 4,4,4-trifluoroacetoacetate in the presence of Cu(OAc)2 and piperidine using a DMSO/H2O (10/1) mixture as solvent.
- Zhang, Jian,Jin, Guanyi,Xiao, Senhan,Wu, Jingjing,Cao, Song
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p. 2352 - 2356
(2013/03/29)
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- Organocatalytic 1,3-dipolar cycloaddition reactions of ketones and azides with water as a solvent
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We reported an enamine catalyzed strategy to fully promote a 1,3-dipolar cycloaddition to access a vast pool of substituted 1,2,3-triazoles with water as the only solvent.
- Yeung, Dwun Kit Jonathan,Gao, Tao,Huang, Jiayao,Sun, Shaofa,Guo, Haibing,Wang, Jian
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p. 2384 - 2388
(2013/09/12)
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- Design, synthesis, and in vitro biological evaluation of 1 H -1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein
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The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC 50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC 50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.
- Cheng, Huimin,Wan, Junting,Lin, Meng-I,Liu, Yingxue,Lu, Xiaoyun,Liu, Jinsong,Xu, Yong,Chen, Jianxin,Tu, Zhengchao,Cheng, Yih-Shyun E.,Ding, Ke
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p. 2144 - 2153
(2012/05/04)
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- Organocatalytic enamide-azide cycloaddition reactions: Regiospecific synthesis of 1,4,5-trisubstituted-1,2,3-triazoles
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Heterocycles in one click: A novel organocatalytic enamide-azide cycloaddition reaction has been developed. This synthetic procedure represents a new method for the efficient construction of 1,4,5-trisubstituted-1,2,3- triazoles under mild reaction condit
- Danence, Lee Jin Tu,Gao, Yaojun,Li, Maoguo,Huang, Yuan,Wang, Jian
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supporting information; experimental part
p. 3584 - 3587
(2011/05/04)
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- N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia
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NHE-1 inhibitors, methods of using such NHE-1 inhibitors and pharmaceutical compositions containing such NHE-1 inhibitors. The NHE-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia.
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- 1H and 13C NMR - Spectroscopy of substituted 1,2,3-triazoles
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1-Aryl-4-carboxy-5-methyl-1,2,3-triazoles were prepared by the condensation of aryl azides with ethyl acetoacetate. The structures of these compounds were characterized by MS, IR and 1H and 13C NMR spectroscopy. The measured and calc
- Sun, Xiao-Wen,Xu, Peng-Fei,Zhang, Zi-Yi
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p. 459 - 460
(2007/10/03)
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