96237-47-7Relevant academic research and scientific papers
Substituted 4-hydroxy-1,2,3-triazoles: synthesis, characterization and first drug design applications through bioisosteric modulation and scaffold hopping approaches
Pippione, Agnese C.,Dosio, Franco,Ducime, Alex,Federico, Antonella,Martina, Katia,Sainas, Stefano,Frolund, Bente,Gooyit, Major,Janda, Kim D.,Boschi, Donatella,Lolli, Marco L.
, p. 1285 - 1292 (2015)
Bioisosterism and scaffold hopping are two widely used approaches in medicinal chemistry for the purpose of lead optimization. The study highlights the physicochemical properties of the 4-hydroxy-1,2,3-triazole scaffold, a less investigated heterocyclic system. Synthetic strategies to obtain different N-substituted 4-hydroxy-1,2,3-triazole isomers are presented, and their role as possible isosteres of the carboxylic acid is discussed. The aim is to use this system to modulate the acidic moieties present in lead compounds and, at the same time, to regiodirect substituents in set directions, through targeted substitution on the three nitrogen atoms of the triazole ring. Through this approach, compounds having enhanced binding affinity, will be sought. Two examples of bioisosteric applications of this moiety are presented. In the first example, a classical bioisosteric approach mimicking the distal (S)-glutamic acid carboxyl group using the 4-hydroxy-1,2,3-triazole moiety is applied, to obtain two promising glutamate analogs. In the second example, a scaffold hopping approach is applied, replacing the phenolic moiety present in MDG-1-33A, a potent inhibitor of Onchocerca volvulus chitinase, with the 4-hydroxy-1,2,3-triazole scaffold. The 4-hydroxy-1,2,3-triazole system appears to be useful and versatile in drug design.
Regioselective N-Alkylation of Ethyl 4-Benzyloxy-1,2,3-triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres
Sainas, Stefano,Pippione, Agnese C.,Giraudo, Alessandro,Martina, Katia,Bosca, Federica,Rolando, Barbara,Barge, Alessandro,Ducime, Alex,Federico, Antonella,Grossert, Stuart J.,White, Robert L.,Boschi, Donatella,Lolli, Marco L.
, p. 501 - 519 (2019/01/04)
Acidic 4-hydroxy-1,2,3-triazole is a proven bioisostere of acidic functions that has recently been used to replace the acidic moieties of biologically active leads. Straightforward chemical strategies for the synthesis of the three possible N-alkylated 4-hydroxy-1,2,3-triazole regioisomers have been designed and reported herein, by identifying the optimal conditions under which the alkylation of ethyl 4-benzyloxy-1,2,3-triazolecarboxylate (compound 19) can be regiodirected to the triazole N(b) position and thus produce the only isomer that cannot be obtained via the cycloaddition reaction. Furthermore, an innovative platform for parallel synthesis, called Arachno and which has been patented by the authors' group, has been used to speed up the process, and an NMR study has been carried out to better understand the reactivity of compound 19 towards the N(b) position. A library of benzyloxy protected 4-hydroxy-1,2,3-triazoles has been prepared using the two strategies: regiodirection for the N(b) and N(c) isomers and cycloaddition for the N(a) isomers; the processes are described herein. The three N-alkylated regioisomer series have been characterized spectroscopically (NMR and MS). The subsequent catalytic hydrogenation of the 4-benzyloxy protective group on the N-alkylated-4-benzyloxy-5-ethoxycarbonyl-1,2,3-triazoles provided the corresponding substituted 4-hydroxy-1,2,3-triazoles.
Studies om 1,2,3-Triazoles. Part 12. Synthesis of 1H-Benzoxepino-1,2,3-triazol-10(5H)-one and 5,6-Dihydrobenzoxocino-1,2,3-triazol-11(1H)-one; Two Novel Heterocyclic Systems.
Buckle, Derek R.,Outred, D. James
, p. 3755 - 3763 (2007/10/02)
The intramolecular Friedel-Crafts cyclization of N-protected 5-benzyloxy- and 5-phenethyloxy-1,2,3-triazole-4-carboxylic acids proceeds in moderate yield to give examples of new seven and eight membered fused oxygen heterocycles.When the protecting group
