42606-36-0Relevant articles and documents
Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study
Pedron, Julien,Boudot, Clotilde,Hutter, Sébastien,Bourgeade-Delmas, Sandra,Stigliani, Jean-Luc,Sournia-Saquet, Alix,Moreau, Alain,Boutet-Robinet, Elisa,Paloque, Lucie,Mothes, Emmanuelle,Laget, Michèle,Vendier, Laure,Pratviel, Geneviève,Wyllie, Susan,Fairlamb, Alan,Azas, Nadine,Courtioux, Bertrand,Valentin, Alexis,Verhaeghe, Pierre
, p. 135 - 152 (2018/06/08)
To study the antiparasitic 8-nitroquinolin-2(1H)-one pharmacophore, a series of 31 derivatives was synthesized in 1–5 steps and evaluated in vitro against both Leishmania infantum and Trypanosoma brucei brucei. In parallel, the reduction potential of all molecules was measured by cyclic voltammetry. Structure-activity relationships first indicated that antileishmanial activity depends on an intramolecular hydrogen bond (described by X-ray diffraction) between the lactam function and the nitro group, which is responsible for an important shift of the redox potential (+0.3 V in comparison with 8-nitroquinoline). With the assistance of computational chemistry, a set of derivatives presenting a large range of redox potentials (from ?1.1 to ?0.45 V) was designed and provided a list of suitable molecules to be synthesized and tested. This approach highlighted that, in this series, only substrates with a redox potential above ?0.6 V display activity toward L. infantum. Nevertheless, such relation between redox potentials and in vitro antiparasitic activities was not observed in T. b. brucei. Compound 22 is a new hit compound in the series, displaying both antileishmanial and antitrypanosomal activity along with a low cytotoxicity on the human HepG2 cell line. Compound 22 is selectively bioactivated by the type 1 nitroreductases (NTR1) of L. donovani and T. brucei brucei. Moreover, despite being mutagenic in the Ames test, as most of nitroaromatic derivatives, compound 22 was not genotoxic in the comet assay. Preliminary in vitro pharmacokinetic parameters were finally determined and pointed out a good in vitro microsomal stability (half-life > 40 min) and a 92% binding to human albumin.
Vicarious nucleophilic amination of nitroquinolines by 1,1,1- trimethylhydrazinium iodide
Grzegozek, Maria
experimental part, p. 1879 - 1882 (2009/06/18)
(Chemical Equation Presented) The amination of 3-, 5-, 6-, 7- and 8-nitroquinoline via the vicarious nucleophilic substitution of hydrogen (VNS) with 1,1,1-trimethylhydrazinium iodide (TMHI) in the presence of t-BuOK in DMSO was studied. The amination occurs regioselectively giving ortho or ortho and para isomers relative to the nitro group with a high yield (95-86%). 2-Nitroquinoline does not undergo vicarious amination but displacement of the labile nitro group by an amino group occurs and then transformation to an imine compound and hydrolysis gives 2(1H)-quinolinone.
ALKALINE HYDROLYSIS OF 2-(TRIFLUOROMETHYL)IMIDAZO AND -QUINOLINES
Moores, Ian G.,Smalley, Robert K.,Suschitzky, Hans
, p. 573 - 580 (2007/10/02)
2-(Trifluoromethyl)imidazo and -quinoline have been prepared from 5(6)-acetamido-2-(trifluoromethyl)benzimidazole and 7,8-diaminoquinoline respectively.These (trifluoromethyl)quinolines like 2-(trifluoromethyl)imidazoles but unlike 2-(trifluoromethyl)benzimidazoles, undergo hydrolysis in dilute sodium hydroxide to give ultimately the corresponding imidazo and -quinoline, respectively.
