Convergent synthesis and cruzain inhibitory activity of novel 2-(N′-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines

Biochemical evaluation of a series of synthetic chalcone and hydrazide derivatives as novel inhibitors of cruzain from Trypanosoma cruzi

“…The chalcones (3)(4)(5)(6) showed yields in the range of 40-50% due the presence of the bromine atom in the starting material acetophenone, which stabilizes the enolate intermediate of the reaction making it less reactive. This effect was not observed for the chalcones (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), which showed yields in the range of 70-98%.…”

“…22 Fluorescence was monitored on a Wallac 1420-042 PerkinElmer spectrofluorometer and measurements were done using 355 nm as the excitation wavelength and 460 nm as the emission wavelength, as previously described. 10 Cruzain activity was measured as an increase of fluorescence intensity of liberated aminocoumarin when Z-Phe-Arg-AMC was used as the substrate. The percentage of inhibition was calculated according to the following equation: % of Inhibition = 100 × (1 − V i / V 0 )…”

“…8,9 As part of our research program aimed at discovering novel T. cruzi cruzain inhibitors, we have synthesized and evaluated a series of chalcones and hydrazides. [10][11][12] …”

Preparation of α,β-unsaturated trifluoromethylketones and their application in the synthesis of heterocycles

“…Most heterocycles were isolated as a single diastereoisomer (E- isomers). 170 N-substituted pyrimidinones 557 were synthesized by condensation of enones 553 with excess N-methyl-and N-allylureas. 171 The reaction of β-alkoxyvinyl CF3 -ketones 553 with 2-methyl-2-thiopseudourea sulfate carried out in the presence of sodium hydroxide solution furnishing substituted 4-CF3-2-methylsulfanyltetrahydropyrimidines 558 in good yields, but the product was unstable and rapidly lost an alcohol and water molecule to give the parent aromatic pyrimidine 559.…”

Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos

“…Das patentes depositadas através da Organização Mundial da Propriedade Intelectual (WIPO -World Intellectual Property Organization) sobre moduladores de rotas metabólicas do T. cruzi, os inibidores de cruzaína merecem especial destaque. As principais classes de inibidores desta enzima incluem (Figura 3): (i) derivados peptídicos (5 e 6); 34 (ii) derivados não-peptídicos (triazóis 7, pirimidinas 8, tiossemicarbazonas 9 e chalconas 10); [34][35][36][37][38][39][40] (iii) complexos de rênio e ouro (oxorênios 11 e ciclometalados de ouro 12); 41 e (iv) doadores de óxido nítrico (nitrosotióis 13 e nitrosilo complexos de ferro e rutênio 14). 42,43 Os derivados peptídicos constituem a classe mais importante de inibidores da cruzaína, especialmente o dipeptidil vinil sulfônico N-metil-Pip-F-hF-VSf (5).…”