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1.
Eur J Med Chem ; 194: 112255, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32244098

RESUMO

Human immunodeficiency virus type 1 (HIV-1) is a public health problem that affects over 38 million people worldwide. Although there are highly active antiretroviral therapies, emergence of antiviral resistant strains is a problem which leads to almost a million death annually. Thus, the development of new drugs is necessary. The viral enzyme reverse transcriptase (RT) represents a validated therapeutic target. Because the oxoquinolinic scaffold has substantial biological activities, including antiretroviral, a new series of 4-oxoquinoline ribonucleoside derivatives obtained by molecular hybridization were studied here. All synthesized compounds were tested against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), and 9a and 9d displayed the highest antiviral activities, with IC50 values of 1.4 and 1.6 µM, respectively. These compounds were less cytotoxic than AZT and showed CC50 values of 1486 and 1394 µM, respectively. Molecular docking studies showed that the most active compounds bound to the allosteric site of the enzyme, suggesting a low susceptibility to the development of antiviral resistance. In silico pharmacokinetic and toxicological evaluations reinforced the potential of the active compounds as anti-HIV candidates for further exploration. Overall, this work showed that compounds 9a and 9d are promising scaffold for future anti-HIV-1 RT drug design.


Assuntos
4-Quinolonas/farmacologia , Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Ribonucleosídeos/farmacologia , 4-Quinolonas/síntese química , 4-Quinolonas/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Relação Dose-Resposta a Droga , Desenho de Fármacos , Transcriptase Reversa do HIV/metabolismo , HIV-1/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Ribonucleosídeos/síntese química , Ribonucleosídeos/química , Relação Estrutura-Atividade
2.
Curr Top Med Chem ; 20(3): 244-255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995008

RESUMO

4-Oxoquinoline derivatives constitute an important family of biologically important substances, associated with different bioactivities, which can be synthesized by different synthetic methods, allowing the design and preparation of libraries of substances with specific structural variations capable of modulating their pharmacological action. Over the last years, these substances have been extensively explored by the scientific community in efforts to develop new biologically active agents, with greater efficiency for the treatment of a variety of diseases. Viral infections have been one of the targets of these studies, although to a lesser extent than other diseases such as cancer and bacterial infections. Nevertheless, the literature provides examples that corroborate with the fact that these substances may act on different pharmacological targets in different viral pathogens. This review provides a compilation of some of the major studies published in recent years showing the discovery and/or development of new antiviral oxoquinoline agents, highlighting, whenever possible, their mechanisms of action.


Assuntos
4-Quinolonas/farmacologia , Antivirais/farmacologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Antivirais/síntese química , Antivirais/química , Desenvolvimento de Medicamentos , Humanos , Estrutura Molecular
3.
Eur J Med Chem ; 143: 710-723, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220792

RESUMO

Gram-positive bacteria are responsible for a broad range of infectious diseases, and the emergency and wide spread of drug-resistant Gram-positive pathogens including MRSA and MRSE has caused great concern throughout the world. 4-Quinolones which are exemplified by fluoroquinolones are mainstays of chemotherapy against various bacterial infections including Gram-positive pathogen infections, and their value and role in the treatment of bacterial infections continues to expand. However, the resistance of Gram-positive organisms to 4-quinolones develops rapidly and spreads widely, making them more and more ineffective. To overcome the resistance and reduce the toxicity, numerous of 4-quinolone derivatives were synthesized and screened for their in vitro and in vivo activities against Gram-positive pathogens, and some of them exhibited excellent potency. This review aims to outlines the recent advances made towards the discovery of 4-quinolone-based derivatives as anti-Gram-positive pathogens agents and the critical aspects of design as well as the structure-activity relationship of these derivatives. The enriched SAR paves the way to the further rational development of 4-quinolones with a unique mechanism of action different from that of the currently used drugs to overcome the resistance, well-tolerated and low toxic profiles.


Assuntos
4-Quinolonas/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
4.
Eur J Med Chem ; 141: 335-345, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29031077

RESUMO

The emergence and wide-spread of drug-resistant bacteria including multi-drug resistant and pan-drug resistant pathogens which are associated with considerable mortality, represent a significant global health threat. 4-Quinolones which are exemplified by fluoroquinolones are the second largest chemotherapy agents used in clinical practice for the treatment of various bacterial infections. However, the resistance of bacteria to 4-quinolones develops rapidly and spreads widely throughout the world due to the long-term, inappropriate use and even abuse. To overcome the resistance and improve the potency, several strategies have been developed. Amongst them, molecular hybridization, which is based on the incorporation of two or more pharmacophores into a single molecule with a flexible linker, is one of the most practical approaches. This review aims to summarize the recent advances made towards the discovery of 4-quinolone hybrids as potential antibacterial agents as well as their structure-activity relationship (SAR). The enriched SAR may pave the way for the further rational development of 4-quinolone hybrids with excellent potency against both drug-susceptible and drug-resistant bacteria.


Assuntos
4-Quinolonas/farmacologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade
5.
Mol Divers ; 21(1): 37-52, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27670880

RESUMO

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].


Assuntos
4-Quinolonas/síntese química , 4-Quinolonas/farmacologia , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Indóis/química , Pirrolidinas/química , 4-Quinolonas/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Ácidos Carboxílicos/química , Técnicas de Química Sintética , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Oxindois , Teoria Quântica , Relação Estrutura-Atividade
6.
Eur J Med Chem ; 126: 408-420, 2017 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-27907877

RESUMO

New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 µM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 µM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes.


Assuntos
4-Quinolonas/síntese química , 4-Quinolonas/farmacologia , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , 4-Quinolonas/química , 4-Quinolonas/metabolismo , Fosfatase Alcalina/química , Domínio Catalítico , Técnicas de Química Sintética , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Relação Estrutura-Atividade
7.
Bioorg Med Chem Lett ; 26(16): 3905-12, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27426300

RESUMO

Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.


Assuntos
4-Quinolonas/química , Antagonistas do Receptor Purinérgico P2X/química , Quinazolinonas/química , Receptores Purinérgicos P2X3/metabolismo , 4-Quinolonas/síntese química , 4-Quinolonas/metabolismo , Trifosfato de Adenosina/metabolismo , Humanos , Concentração Inibidora 50 , Ligação Proteica , Antagonistas do Receptor Purinérgico P2X/síntese química , Antagonistas do Receptor Purinérgico P2X/metabolismo , Quinazolinonas/metabolismo , Receptores Purinérgicos P2X3/química , Relação Estrutura-Atividade
8.
J Enzyme Inhib Med Chem ; 31(5): 796-809, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26226179

RESUMO

The potential antitumor activities of a series of 7-(4-substituted piperazin-1-yl)fluoroquinolone derivatives (1-14a,b) using ciprofloxacin and norfloxacin as scaffolds are described. These compounds exhibit potent and broad spectrum antitumor activities using 60 human cell lines in addition to the inherent antibacterial activity. Compounds 1a, 2a, 3b, 6b and 7a were found to be the most potent, while 2b, 5b, and 6a were found to have an average activity. The results of this study demonstrated that compounds 1a, 2a, 3b, 6b and 7a (mean GI50; 2.63-3.09 µM) are nearly 7-fold more potent compared with the positive control 5-fluorouracil (mean GI50; 22.60 µM). More interestingly, compounds 1a, 2a, 3b, 6b and 7a have an almost antitumor activity similar to gefitinib (mean GI50; 3.24 µM) and are nearly 2-fold more potent compared to erlotinib (mean GI50; 7.29 µM). In silico study and ADME-Tox prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.


Assuntos
4-Quinolonas/síntese química , 4-Quinolonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ciprofloxacino/química , Simulação por Computador , Norfloxacino/química , 4-Quinolonas/química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células , Humanos , Estrutura Molecular , Piperazina , Piperazinas/síntese química , Piperazinas/química , Piperazinas/farmacologia , Relação Estrutura-Atividade
9.
Org Lett ; 17(5): 1268-71, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25700137

RESUMO

A novel, metal-free oxidative intramolecular Mannich reaction was developed between secondary amines and unmodified ketones, affording a simple and direct access to a broad range of 2-arylquinolin-4(1H)-ones through C(sp(3))-H activation/C(sp(3))-C(sp(3)) bond formation from readily available N-arylmethyl-2-aminophenylketones, using TEMPO as the oxidant and KO(t)Bu as the base.


Assuntos
4-Quinolonas/síntese química , Compostos de Anilina/química , Cetonas/química , Elementos de Transição/química , 4-Quinolonas/química , Catálise , Estrutura Molecular , Oxirredução
10.
J Org Chem ; 80(3): 1464-71, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25575042

RESUMO

A palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence for the preparation of functionalized 4-quinolones from 2-iodoanilines and alkynes via two different protocols is described. The first method (A) yields the cyclized products after only 20 min of microwave (MW) heating at 120 °C. The second method (B) is a gas-free one-pot two-step sequence which runs at room temperature, allowing the use of sensitive substituents (e.g., nitro and bromide groups). For both protocols, molybdenum hexacarbonyl was used as a solid source of CO.


Assuntos
4-Quinolonas/síntese química , Molibdênio/química , Nitrocompostos/química , 4-Quinolonas/química , Alquinos/química , Ciclização , Indóis/química , Micro-Ondas , Estrutura Molecular , Paládio/química , Temperatura
11.
Org Biomol Chem ; 12(48): 9789-92, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25371139

RESUMO

Primary amino acids are found to be good enantioselective catalysts for the direct asymmetric Mannich reaction between 2-amino acetophenone and aldehydes. The 2-aryl-2,3-dihydro-4-quinoline products are obtained in moderate to good yields and good to high enantioselectivities with 10 mol% of the primary amino acid catalyst under mild reaction conditions.


Assuntos
4-Quinolonas/síntese química , Aminoácidos/química , 4-Quinolonas/química , Catálise , Estrutura Molecular
12.
Org Biomol Chem ; 12(42): 8555-61, 2014 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-25245989

RESUMO

A new strategy was developed to synthesize 1,2-disubstituted 4-quinolones in good yield starting from 1,3-bisaryl-monothio-1,3-diketone substrates. The synthesized compounds were evaluated for antimalarial activity using Plasmodium falciparum strains. All compounds, except for two, showed good activity. Of these, seven compounds exhibited an excellent antimalarial activity (IC50, <2 µM). More importantly, all seven compounds were equally effective in inhibiting the growth of both chloroquine-sensitive and chloroquine-resistant strains. The cytotoxicity assessment using carcinoma and non-carcinoma human cell lines revealed that almost all synthesized compounds were minimally cytotoxic (IC50, >50 µM).


Assuntos
4-Quinolonas/síntese química , 4-Quinolonas/farmacologia , Antimaláricos/síntese química , Antimaláricos/farmacologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , 4-Quinolonas/química , Antimaláricos/química , Linhagem Celular , Linhagem Celular Tumoral , Humanos
13.
J Mol Model ; 20(9): 2431, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25138375

RESUMO

The synthesis of 2-aryl-2,3-dihydro-4-quinolones in the presence of per-6-amino-ß-cyclodextrin (per-6-ABCD) as catalyst can improve selectivity and yield. The interaction between per-6-ABCD and benzaldehyde or o-aminoacetophenone plays an important role in this reaction. This paper studies the complexes of per-6-ABCD with benzaldehyde and o-aminoacetophenone using density functional theory (DFT) method. The reaction process is investigated by studying the energy of the reactants and the product. Hydrogen bonds are researched on the basis of natural bonding orbital (NBO) analysis, the results propose the donor-acceptor interactions of complex. The Mulliken charge and frontier orbital are employed for revealing the charge distribution. In addition, (13)C nuclear magnetic resonance ((13)CNMR) spectroscopy shows that the carbon atom on the aldehyde group for benzaldehyde, carbonyl group and the carbon atom connected with carbonyl group for o-aminoacetophenone are apparently activated in the cavity of per-6-ABCD. The probable catalytic mechanism of per-6-ABCD is discussed in terms of the calculated parameters.


Assuntos
4-Quinolonas/síntese química , Simulação por Computador , Modelos Químicos , Modelos Moleculares , beta-Ciclodextrinas/química , Acetofenonas/química , Benzaldeídos/química , Catálise , Transferência de Energia , Ligação de Hidrogênio , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade
14.
Org Biomol Chem ; 12(32): 6094-104, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24909330

RESUMO

Recent studies have shown that compounds based on a (2-nitrophenyl)methanol scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The most promising molecule displayed anti-biofilm activity and a tight-binding mode of action. Herein, we report on the convenient synthesis and biochemical evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The in vitro potency of these inhibitors against recombinant PqsD as well as the effect of selected compounds on the production of the signal molecules HHQ and PQS in P. aeruginosa were examined. The gathered data allowed the establishment of a structure-activity relationship, which was used to design fluorescent inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol derivatives with improved in cellulo efficacy providing new perspectives towards the application of PqsD inhibitors as anti-infectives.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Metanol/farmacologia , Pseudomonas aeruginosa/citologia , Pseudomonas aeruginosa/metabolismo , 4-Quinolonas/síntese química , 4-Quinolonas/química , Proteínas de Bactérias/metabolismo , Metanol/química , Mutação , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-Atividade
15.
Bioorg Med Chem ; 22(14): 3670-83, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24906513

RESUMO

Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.


Assuntos
4-Quinolonas/farmacologia , Ácidos Carboxílicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , 4-Quinolonas/síntese química , 4-Quinolonas/química , Animais , Células CHO , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Linhagem Celular , Cricetulus , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
16.
Bioorg Med Chem Lett ; 24(4): 1214-7, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24468411

RESUMO

Treatment of 4-hydroxyquinolines with (2-methyl)allyl bromide in the presence of K2CO3 resulted in the formation of novel N-[(2-methyl)allyl]-4-quinolones through selective N-alkylation. Further reaction of N-(2-methylallyl)-4-quinolones with bromine or N-bromosuccinimide yielded the corresponding 3-bromo-1-(2,3-dibromo-2-methylpropyl)-4-quinolones and 3-bromo-1-(2-methylallyl)-4-quinolones, respectively. Furthermore, a copper-catalyzed C-N coupling of the latter 3-bromo-4-quinolones with (5-chloro)indole afforded novel 3-[(5-chloro)indol-1-yl]-4-quinolone hybrids. Antifungal and antiplasmodial assays of all new 4-quinolones were performed and revealed no antifungal properties but moderate antiplasmodial activities. All 15 compounds displayed micromolar activities against a chloroquine-sensitive strain of Plasmodium falciparum, and the five most potent compounds also showed micromolar activities against a chloroquine-resistant strain of P. falciparum with IC50-values ranging between 4 and 70 µM.


Assuntos
4-Quinolonas/farmacologia , Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , Animais , Antimaláricos/síntese química , Antimaláricos/química , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
17.
Bioorg Med Chem Lett ; 23(16): 4597-601, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23850203

RESUMO

The 1,4-dihydro-4-oxoquinoline ribonucleoside, Neq135, is the first low micromolar trypanosomatidae inhibitor to show good ligand efficiency (0.28 kcal mol(-1)atom(-1)) and good ligand lipophilicity efficiency (0.37 kcal mol(-1)atom(-1)) when acting against Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH). This and other six ribonucleosides were synthesized using our in-house technology, and assayed against the GAPDH NAD(+) site using isothermal titration calorimetry (ITC). Compound Neq135 had acceptable in vitro cytotoxicity, inhibited TcGAPDH with a Ki(app) value of 16 µM and killed the trypomastigote form of Trypanosoma cruzi Tulahuen strain with a concentration similar to that displayed by the control drug benznidazole. Neq135 is tenfold lower kinetic affinity against hGAPDH and does not kill Balb-c fibroblast nor spleen mouse cells. These results emphasize the possibility of integrating ligand- and target-based designs to uncover potent and selective TcGAPDH inhibitors that expands the opportunity for further medicinal chemistry endeavor towards NAD(+) TcGAPDH site.


Assuntos
Desenho de Fármacos , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Ribonucleosídeos/síntese química , Ribonucleosídeos/farmacologia , Tripanossomicidas , Trypanosoma cruzi/efeitos dos fármacos , 4-Quinolonas/síntese química , 4-Quinolonas/química , 4-Quinolonas/farmacologia , Animais , Células 3T3 BALB , Fibroblastos/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Ribonucleosídeos/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/farmacologia
18.
Chem Commun (Camb) ; 49(46): 5313-5, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23640202

RESUMO

A novel one-pot synthesis of the 2-substituted 3-carboxy-4-quinolone/chromone derivatives from readily available 3-oxo-3-arylpropanoates and amides/acyl chlorides is reported, without any transition metal aid.


Assuntos
4-Quinolonas/síntese química , Cromonas/síntese química , 4-Quinolonas/química , Amidas/química , Técnicas de Química Sintética , Cloretos/química , Cromonas/química , Propionatos/química
19.
J Org Chem ; 78(2): 744-51, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23245355

RESUMO

A highly efficient one-pot synthesis of enantiomerically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been carried out for the first time using per-6-ABCD as a supramolecular host, chiral base catalyst, and a reusable promoter to give the corresponding scaffold with high yield (up to 99%) and enantiomeric excess (up to 99%). The catalyst is recovered and reused without loss in its activity.


Assuntos
4-Quinolonas/síntese química , beta-Ciclodextrinas/química , 4-Quinolonas/química , Catálise , Estrutura Molecular , Estereoisomerismo
20.
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