Library of 1,4-Disubstituted 1,2,3-Triazole Analogs of Oxazolidinone RNA-Binding Agents

Abstract

The design and synthesis of small molecules that target RNA is immensely important in antibacterial therapy. We had previously reported on the RNA binding of a series of 4,5-disubstituted 2-oxazolidinones that bind to a highly conserved bulge region of bacterial RNA. This biological target T box antitermination system, which is found mainly in Gram-positive bacteria, regulates the expression of several amino acid related genes. In an effort to amplify our library, we have prepared a library of 1,4-disubstituted 1,2,3-triazole analogs that entails an isosteric replacement of the oxazolidinone nucleus. The synthesis of the new analogs was enhanced via copper(I) catalysis of an azide and alkyne cycloaddition reaction. A total of 108 1,4-disubstituted 1,2,3-triazole compounds have been prepared. All compounds were evaluated as RNA binding agents.

Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites

“…The following acetylenes are commercially available: phenylacetylene, trimethylsilylacetylene, 2-ethynylanisole, while the remaining three acetylenes 3-methyl-1-(prop-2-ynyl)-1H-pyrazole, 1-phenyl-4-(prop-2-ynyl)piperazine and 4-(prop-2-ynyl)-morpholine were prepared according to Refs. 14,15. …”

Design, chemical synthesis and biological evaluation of 3-spiromorpholinone/3-spirocarbamate androsterone derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase type 3

“…Thus, the steroidal triazolic compound 6e20 was obtained by 1,3-dipolar cycloaddition of the terminal alkyne 6e18 with benzyl azide. 33 It is well known that the 1,4-triazole regioisomer is exclusively obtained from catalysis with copper (I). [34][35][36] The sulfonamide 6e21 and the carboxamide 6e22 were also synthesized by nucleophilic substitution under conditions depicted in Scheme 3 and using benzyl sulfonyl chloride and benzoyl chloride, respectively.…”

Synthesis and Stereospecificity of 4,5-Disubstituted Oxazolidinone Ligands Binding to T-box Riboswitch RNA

“…10 We recently reported lead oxazolidinone compounds that act as molecular effectors of T-box riboswitch function. 11,12 As part of a comprehensive effort to design and develop potential medicinal agents for disrupting the T-box riboswitch, 11-15 we wished to investigate the details of the binding interaction between these lead oxazolidinones and their target, the T-box antiterminator RNA structural element.…”