768-03-6Relevant articles and documents
Copper-catalyzed three-component: N -alkylation of quinazolinones and azoles
Deng, Guo-Jun,Huang, Huawen,Ji, Xiaochen,Wang, Chunlian
supporting information, p. 1200 - 1204 (2022/02/21)
A Cu-catalyzed three-component N-alkylation coupling reaction of N-heteroarenes with methyl ketones and DMPA as a carbon source has been developed. Using methyl ketones as alkylation reagents and DMPA (N,N′-dimethylpropionamide) as a carbon source, the re
Diastereoselective Photoredox-Catalyzed [3 + 2] Cycloadditions of N-Sulfonyl Cyclopropylamines with Electron-Deficient Olefins
White, Dawn H.,Noble, Adam,Booker-Milburn, Kevin I.,Aggarwal, Varinder K.
supporting information, p. 3038 - 3042 (2021/05/04)
A highly diastereoselective, visible-light-induced [3 + 2] cycloaddition between N-sulfonyl cyclopropylamines and electron-deficient olefins is reported. The reactions proceed via the oxidation of a sulfonamide aza-anion by an organic photocatalyst to generate a nitrogen-centered radical. Strain-induced ring opening and intermolecular addition to the olefin generate an intermediate carbon-centered radical that is reduced to an anion prior to 5-exo cyclization. This enables a highly diastereoselective construction of trans-cyclopentanes possessing synthetically useful functional groups.
Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
Atherton, Richard L.,Kelly, John M.,Olmo, Francisco,Sanz-Serrano, Julen,Alcolea, Verónica,Beltran-Hortelano, Iván,Pérez-Silanes, Silvia,Rubio-Hernández, Mercedes
, (2021/07/14)
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline.
