67756-04-1Relevant academic research and scientific papers
Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
Beltran-Hortelano, Iván,Atherton, Richard L.,Rubio-Hernández, Mercedes,Sanz-Serrano, Julen,Alcolea, Verónica,Kelly, John M.,Pérez-Silanes, Silvia,Olmo, Francisco
, (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.
Direct Synthesis of γ-Keto Sulfones from Allylic Alcohols: One-Pot Palladium(II)-Catalyzed Generation of Enones Followed by Water-Mediated 1,4-Addition of Organosulfinates
Vellakkaran, Mari,Andappan, Murugaiah M. S.,Nagaiah, Kommu,Nanubolu, Jagadeesh Babu
supporting information, p. 3575 - 3583 (2016/07/28)
Allylic alcohols were exploited as synthetic precursors of γ-keto sulfones. The reaction involved the one-pot generation of α,β-enones in situ from the allylic alcohols by using a PdII–dioxygen catalytic system and subsequent sulfa-Michael addition in the presence of water. Importantly, water was identified as a sustainable substitute for a toxic copper salt to promote organosulfonyl addition. Diverse examples of aromatic and aliphatic γ-keto sulfones were prepared. Specially, Ar–X (X = Br, Cl) bonds were tolerated, which indicated a chemoselective catalytic system for the preparation of halogen-bearing γ-keto sulfones. This one-pot method does not require an acid, a base, or isolation of any intermediate. Control experiments indicated that the active catalyst of the first step also promoted the subsequent C–S bond-formation reaction. Water was found to accelerate the reaction rate and to be involved in the protonolysis of the σ-alkylpalladium complex, as corroborated by deuterium incorporation.
Scope of the suzuki-miyaura cross-coupling reaction of potassium trifluoroboratoketohomoenolates
Molander, Gary A.,Jean-Gerard, Ludivine
supporting information; experimental part, p. 1297 - 1303 (2009/06/28)
Potassium trifluoroboratoketohomoenolates were prepared in good yields from either the corresponding α,β-unsaturated compounds or methyl ketones. These organoboron reagents were effectively cross-coupled with various aryl and heteroaryl chlorides.
Synthesis of 1,4-bis-(2,4-dimethoxyphenyl)-2,3-bis-(4-methoxybenzyl)butane-1,4-dione
Balram,Ram,Ram, S. Raghu
, p. 843 - 845 (2007/10/03)
The synthesis of meso and racemic 1,4-bis-(2,4-dimethoxyphenyl)-2,3-bis-(4-methoxybenzyl)-butane-1,4-dione, a brackenin like molecule from commercially available 2,4-dimethoxybenzaldehyde is described.
A new synthesis of flavonoids via Heck reaction
Bianco, Armandodoriano,Cavarischia, Claudia,Farina, Angela,Guiso, Marcella,Marra, Carolina
, p. 9107 - 9110 (2007/10/03)
Several naturally occuring flavonoids have been synthesised following a new proposed method based on the use of the Heck reaction. The key step involves the coupling of an aryl vinyl ketone with an aryl iodide. This procedure affords the flavonoid moiety in a single step.
Reactions of β-ethylsulfanylpropionyl tetrafluoroborate with electron-rich aromatics: A novel synthesis of aryl vinyl ketones
Lebedev, Mikhail V.,Nenajdenko, Valentine G.,Balenkova, Elizabeth S.
, p. 89 - 93 (2007/10/03)
A new synthesis of aryl vinyl ketones is described. The acylation of active aromatics with the complex of β-ethylsulfanylpropionyl fluoride 1 and boron trifluoride leads to formation of 1-aryl-3-(ethylsulfanyl)propan-1-ones. Subsequent methylation with methyl triflate and elimination with an aqueous solution of KHCO3 results in formation of aryl vinyl ketones in 86-99% yield.
The Synthesis of Indan-1-ones and Isocoumarins
Carter, Rachel H.,Garson, Mary J.,Hill, Robert A.,Staunton, James,Sunter, David C.
, p. 471 - 479 (2007/10/02)
A flexible synthetic route leading via indan-1-ones to variously methylated and oxygenated isocoumarins is described.The indanones are prepared by alternative routes involving intramolecular Friedel-Crafts cyclisation of arylpropionic acids or pericyclic ring closure of acrylophenones.The influence of substitution on the rate of the pericyclic reaction is assessed.
