Synthesis of 2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one derivatives using trifluoroacetimidoyl chlorides

López

Rodríguez

et al. 2018

Archiv der Pharmazie

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Trifluoromethyl-substituted quinolones and their analogues have emerged as an interesting platform in the last 6 years to design antiparasite agents. Many of their derivatives have been demonstrated to display excellent efficacy against flagellate parasites such as Plasmodium spp. In order to identify new analogues of trifluoromethyl-substituted quinolones to treat the American cutaneous leishmaniasis, we evaluated the antiproliferative activity of a series of 2-(trifluoromethyl)benzo[b]-[1,8]naphthyridin-4(1H)-ones on the Leishmania braziliensis and Leishmania mexicana parasites. The mentioned derivatives have never been evaluated against any parasite strain. In general, an in vitro evaluation on L.(L)mexicana and L.(V)braziliensis showed that L.(L)mexicana was more sensitive to the action of the compounds than L.(V)braziliensis, either in the promastigote or in the amastigote form. Five compounds exhibited moderate efficacy against L.(L)mexicana promastigotes, with IC values ranging from 9.65 to 14.76 µM. From the mentioned molecules, three compounds, 1e, 1f, and 1h, showed a discrete response against axenic and intracellular amastigotes, with LD values between 19 and 24 µM. Moreover, an in vitro evaluation was performed on an antimony-resistant amastigote strain and a human isolate amastigote strain. These three compounds showed discrete toxicity on peritoneal macrophages; however, their relatively good antiamastigote response compared to the drug glucantime promoted our trifluoromethyl-substituted benzo[b][1,8]naphthyridin-4(1H)-ones as a potential platform to design potent antileishmanial agents.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antileishmanial activity, structure–activity relationship of series of 2‐(trifluoromethyl)benzo[b][1,8]naphthyridin‐4(1H)‐ones

López

Rodríguez

et al. 2018

Archiv der Pharmazie

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“…N 1 -aryl-2-(trifluoromethyl)-7-methoxybenzo[ b ][1,8]naphthyridin-4(1 H )-ones 3j and 3k were employed as high CT dyes, whereas N 1 -phenyl-2-(trifluoromethyl)-benzo[ b ][1,8]naphthyridin-4(1 H )-one 3g was used as the low CT dye (Scheme B and Table S1). All N 1 -aryl-7-methoxy-2-(trifluoromethyl) benzo[ b ][1,8]naphthyridine-4(1 H )-ones 3g , 3j , and 3k were previously prepared by our group following a synthetic strategy of successive steps , The fluorescent profile of the mentioned p K a probes were previously studied by our group, and some key photophysical properties are listed in Table S1. All Brønsted acids were purchased from commercial sources (Sigma-Aldrich, Fluka, or Merck), and they were used without further purification.…”

Section: Methodsmentioning

confidence: 99%

High CT-Fluorophore Featuring a Basic Moiety into D–A Chain as a pK_a Probe

Cerecetto

2022

J. Org. Chem.

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The determination of acidity represents a significant challenge within fluorometry, and no effective strategy has been developed successfully yet. It is attributed to the fact that acidity tends to be enhanced upon excitation, giving, in general, an overestimation of the ionization constant, pK a . Herein, we developed a strategy for pK a estimation of Brønsted acids in solution through fluorometry by using a convenient pK a probe, N 1 -aryl-7-methoxy-2-(trifluoromethyl)benzo [b][1,8]naphthyridin-4(1H)-one. It allowed us to obtain a linear log K SV versus pK a correlation derived from the selective quenching response of the probe by an interaction with different Brønsted acids. The key points of N 1 -aryl-7-methoxy-2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one as a pK a probe were (i) the location of a weak basic moiety in the donor−acceptor chain of the fluorophore, which favors a selective quenching of the intramolecular charge-transfer process according to the acidity of acid, and (ii) the high CT character upon excitation that promotes higher quenching magnitudes and favors a wider pK a range (19.5pK a ) for the log K SV versus pK a correlation. Other key principles were to delimit the study to pure proton transfer and nonfluorescent acids, which allowed restricting the quenching response to a process dependent mainly on the acid−base equilibrium. All these findings open a new perspective as a proof of concept to design effective fluorescent pK a probes.

“…The compounds were prepared following a protocol reported by the group (Scheme S1). Intermediate of 2-chloro-3-acetylquinolines 1 were prepared through the successive reaction (3 steps) from the corresponding acetalinides . The N -phenyl trifluoroacetimidoyl chloride 2 was prepared from Uneyama’s protocol .…”

Section: Methodsmentioning

confidence: 99%

Photo-Induced Partially Aromatized Intramolecular Charge Transfer

Piro

et al. 2021

J. Phys. Chem. B

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Diverse models of intramolecular charge transfer (ICT) have been proposed for interpreting the origin of the charge-transfer (CT) state in donor–acceptor (D–A) dyes. However, a large variety of fused-heterocyclic dyes containing a pseudo-aromatic ring in the rigid structure have shown to be incompatible with them. To approximate a solution within the ICT concept, we reported a novel ICT model called partially aromatized intramolecular charge transfer (PAICT). PAICT involves the generation of a CT state from an ICT that occurred within a pre-excited D–A fused-heterocyclic structure possessing a pseudo-aromatic or unstable aromatic ring as the acceptor moiety. The model was proposed from the multiple-emissive mesomeric D–A N 1 -aryl-2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one, whose excited mesomeric states, which are defined by the aromatic and pseudo-aromatic forms of the pyrindin-4(1H)-one ring, led to a common partial aromatized CT state upon excitation via PAICT. The latter was supported through theoretical calculations on the excited mesomeric states, one-dimensional (1D) and two-dimensional (2D) excitation–emission measurements in different solvents, and the detection of three excited states by lifetime measurements upon 370 nm excitation. The existence of mesomerism was supposed from: (i) two overlapping bands at 370–390 (or 400–420 nm) in UV–vis spectra, (ii) the direct interaction between the pyridinic nitrogen of one molecule and the carbonylic oxygen of the other found in the solid state and, (iii) the detection of three excited states by lifetime measurements. The PAICT opens new perspectives for interpreting the charge-transfer phenomenon in fused-heterocyclic dyes, in particular, those containing a pseudo-aromatic or unstable aromatic ring as an acceptor moiety.