4967-77-5Relevant articles and documents
One-pot microwave-assisted solvent free synthesis of simple alkyl 1,2,3-triazole-4-carboxylates by using trimethylsilyl azide
Taherpour, Avat Arman,Kheradmand, Khojasteh
, p. 131 - 133 (2009)
A fast one-pot microwave-assisted solvent free synthesis of simple alkyl 1,2,3-triazole-4-carboxylate derivatives by 1,3-dipolar cycloaddition reactions with trimethylsilyl azide (Me3Si-N3) on the alkylpropiolates and DMAD in high yi
Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors
Janssen, Antonius P.A.,Van Hengst, Jacob M.A.,Béquignon, Olivier J.M.,Deng, Hui,Van Westen, Gerard J.P.,Van Der Stelt, Mario
, p. 7910 - 7922 (2019/10/11)
Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.
Design, synthesis, and antiviral activity of new 1H-1,2,3-triazole nucleoside ribavirin analogs
De Lourdes G. Ferreira, Maria,Pinheiro, Luiz C. S.,Santos-Filho, Osvaldo A.,Pecanha, Marta D. S.,Sacramento, Carolina Q.,Machado, Viviane,Ferreira, Vitor F.,Souza, Thiago Moreno L.,Boechat, Nubia
, p. 1501 - 1511 (2014/03/21)
Ribavirin is a broad antiviral compound with demonstrated activity against herpes simplex virus (HSV), human immunodeficiency virus HIV-1, influenza virus, respiratory syncytial virus, and hepatitis C virus, among other viruses. However, routine clinical use of ribavirin is limited because this compound is considerably cytotoxic. Herein, we describe the design, synthesis, and antiviral activity of new nucleoside ribavirin analogs based on the following: (1) ring bioisosterism of a 1,2,4-triazole for a 1,2,3-triazole; (2) amide group exchange for other substituents, such as c-propyl, methyl carboxylate, or trifluoromethyl groups; and (3) the ribofuranose remained linked to the triazole ring. Compounds 5a-c were obtained with yields of 65-36 % and tested against Influenza A and HSV-1 replication as well as reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1 RT). Compound 5b (R = CO 2CH3) was the most effective analog, with IC50 values 14 and 3.8 μM for Influenza A and HIV-1 RT, respectively.
Debenzylation of functionalized 4- and 5-substituted 1,2,3-triazoles
Farooq, Tahir,Sydnes, Leiv K.,Toernroos, Karl W.,Haug, Bengterik
experimental part, p. 2070 - 2078 (2012/08/07)
A range of 4- and 5-substituted N-benzyl-1,2,3-triazoles have been submitted to debenzylation using Pd/C and hydrogen in the presence of 1,1,2-trichloroethane. Triazoles with oxygen-containing substituents are efficiently debenzylated under these conditio
