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1.
iScience ; 21: 695-705, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31733515

RESUMO

Rh-catalyzed, highly enantioselective (up to 99.8% ee) synthesis of aliphatic sulfonyl fluorides was accomplished. This protocol provides a portal to a class of novel 2-aryl substituted chiral sulfonyl fluorides, which are otherwise extremely difficult to access. This asymmetric synthesis has the feature of mild conditions, excellent functional group compatibility, and wide substrate scope (51 examples) generating a wide array of structurally unique chiral ß-arylated sulfonyl fluorides for sulfur(VI) fluoride exchange (SuFEx) click reaction and drug discovery.

2.
Org Lett ; 21(21): 8657-8661, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603334

RESUMO

We discovered that with the promotion of sulfuryl fluoride, the carbonyl groups of amides performed as nucleophiles while the hydroxyl groups of alcohols were activated to functionalize as electrophiles. This study displayed that the amide C-N bonds could be easily cleaved with delicate nucleophiles to form the ester C-O bonds at room temperature without using transition metals. The broad substrate scope and excellent functional group compatibility were proved with 44 examples in up to 99% yields.

3.
Eur J Med Chem ; 181: 111566, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401538

RESUMO

The worldwide increase of AIDS, an epidemic infection in constant development has an essential and still requires potent antiretroviral chemotherapeutic agents for reducing the integer of deaths caused by HIV. Thus, there is an urgent need for new anti-HIV drug candidates with increased strength, new targets, superior pharmacokinetic properties, and compact side effects. From this viewpoint, we first review present strategies of anti-HIV drug innovation and the synthesis of heterocyclic or natural compound as anti-HIV agents for facilitating the development of more influential and successful anti-HIV agents.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/síntese química , Técnicas de Química Sintética/métodos , Desenho de Drogas , Descoberta de Drogas , Humanos , Modelos Moleculares , Relação Estrutura-Atividade
4.
Beilstein J Org Chem ; 15: 1907-1912, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467612

RESUMO

A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics.

5.
Eur J Med Chem ; 181: 111598, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415981

RESUMO

A class of novel δ-sulfonolactone-fused pyrazole scaffold was prepared via sulfur (VI) fluoride exchange (SuFEx) chemistry using aryl sulfonyl fluorides and pyrazolones. Enzyme screening revealed their cholinesterase inhibitory activity, among them, compounds 4a, 5a and 5d were identified as highly selective submicromolar BuChE inhibitors (IC50 = 0.20, 0.46 and 0.42 µM, respectively), which exhibited nontoxicity, lipophilicity and remarkable neuroprotective activity. Kinetic studies showed that BuChE inhibition of compounds 5a and 5d was reversible, mixed-type and non-competitive inhibition against BuChE (Ki = 145 nM and 60 nM, respectively). Compound 5d can be accommodated into hBuChE via π-S interaction and hydrophobic interactions. The title compounds are potentially symptomatic treatment in progressive Alzheimer's disease.


Assuntos
Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Inibidores da Colinesterase/síntese química , Desenho de Drogas , Humanos , Simulação de Acoplamento Molecular , Naftalenossulfonatos/síntese química , Naftalenossulfonatos/química , Naftalenossulfonatos/farmacologia , Pirazóis/síntese química , Relação Estrutura-Atividade
6.
Bioorg Chem ; 89: 103015, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158576

RESUMO

A series of (hetero)arylethenesulfonyl fluorides (1-58) were synthesized and screened for their in vitro antioxidant (DPPH, ABTS and DMPD methods) and anti-inflammatory activities. The results revealed that compounds 4, 15, 16, 24, 25, 26, 38, 39, 40, and 54 exhibited excellent antioxidant activity using all the three performed antioxidant methods, which were superior to the standard antioxidants ascorbic acid and gallic acid. Compounds 6-9, 11, 18, 19, 21, 22, 30, 39, 40, 44, 45, 48-50, 54, 55 and 57 displayed promising anti-inflammatory activity, which were better than the reference drug indomethacin. Preliminary structure-activity relationship (SAR) revealed that compounds containing electron donating (OH and OCH3) groups on the phenyl ring possessed excellent antioxidant properties while compounds containing electron-withdrawing (Cl, NO2, F and Br) groups on the phenyl ring were found to be most potent anti-inflammatory agents. The presence of SO2F group played a crucial role in increases both antioxidant and anti-inflammatory activities.

7.
Beilstein J Org Chem ; 15: 976-980, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164935

RESUMO

A catalyst-free novel and efficient methodology for the challenging synthesis of benzo-oxetes from 2'-hydroxyacetophenones mediated by sulfuryl fluoride (SO2F2) gas has been realized. The combination of 2'-hydroxyacetophenones and SO2F2 furnishes synthetically challenging benzo-oxetanes in moderate to excellent yields. The highlight of this work is the design and synthesis of strained four-membered oxete rings.

8.
Org Lett ; 21(12): 4495-4499, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31187997

RESUMO

A Rh(III)-catalyzed annulative insertion of ethylene onto picolinamides was achieved, providing a portal to a class of unique pyridine-containing molecules bearing a terminal olefin moiety for diversification. Application of this method for modification of Sorafenib was also accomplished.

9.
Org Biomol Chem ; 17(20): 5001-5008, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31066433

RESUMO

The construction of a class of novel N-heterocyclic molecules containing both pyrazole and fluorosulfate functionalities was achieved through the reactions of pyrazolones with SO2F2 in good to excellent yields. The fluorosulfate moieties were utilized as versatile building blocks in the Suzuki coupling reaction and SuFEx click chemistry.

10.
Chem Commun (Camb) ; 55(44): 6273-6276, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31086910

RESUMO

The construction of para-amino-arylfluorosulfates was achieved through installation of fluorosulfate (-OSO2F) functionality into aromatic C(sp2)-H bonds by the reaction of N-arylhydroxylamine with sulfuryl fluoride (SO2F2). This method provides a mild process for the preparation of broadly applicable fluorosulfate moieties without the requirement of phenols or transition metals.

11.
Org Biomol Chem ; 17(16): 4087-4101, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30957817

RESUMO

The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.


Assuntos
Amidas/química , Aminas/química , Ácidos Carboxílicos/química , Peptídeos/química , Ácidos Sulfínicos/química , Temperatura Ambiente , Química Click , Estrutura Molecular
12.
Eur J Med Chem ; 173: 117-153, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30995567

RESUMO

At present more than 250 FDA approved chlorine containing drugs were available in the market and many pharmaceutically important drug candidates in pre-clinical trials. Thus, it is quite obvious to expect that in coming decades there will be an even greater number of new chlorine-containing pharmaceuticals in market. Chlorinated compounds represent the family of compounds promising for use in medicinal chemistry. This review describes the recent advances in the synthesis of chlorine containing heterocyclic compounds as diverse biological agents and drugs in the pharmaceutical industries for the inspiration of the discovery and development of more potent and effective chlorinated drugs against numerous death-causing diseases.


Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Inibidores de Glicosídeo Hidrolases/farmacologia , Hidrocarbonetos Clorados/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antimaláricos/síntese química , Antimaláricos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrocarbonetos Clorados/síntese química , Hidrocarbonetos Clorados/química , Estrutura Molecular
13.
J Org Chem ; 84(9): 5803-5812, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-30868885

RESUMO

A simple, mild, and practical process for direct conversion of aldehydes to nitriles was developed feathering a wide substrate scope and great functional group tolerability (52 examples, over 90% yield in most cases) using inorganic reagents (NH2OH/Na2CO3/SO2F2) in DMSO. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable nitriles in a pot, atom, and step-economical manner without transition metals. This protocol will serve as a robust tool for the installation of cyano-moieties to complicated molecules.

14.
Chem Commun (Camb) ; 55(19): 2845-2848, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30768105

RESUMO

A novel, simple and practical method for mild, efficient, cost-effective and regioselective synthesis of highly valuable 1,5-diaryl-1,2,3-triazoles was achieved through dehydrative annulation of readily available alcohols with aryl azides. The reaction proceeded at room temperature, without any metal catalysts, exhibiting excellent compatibility to a large variety of functional groups (>50 examples), resulting in up to quantitative yields.

15.
Bioorg Chem ; 86: 513-537, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30782571

RESUMO

Cancer is the second most important cause of death worldwide. There is always a demand for new anticancer drugs and continuously a wide variety of natural and synthetic compounds were developed by the researchers. Nowadays, a large number of drugs in clinical practice were found to have a high incidence of side effect and multidrug conflict. The development of novel less toxic, low cost and very energetic N-methylpicolinamide-bearing hybrids is a hot research topic in the community of medicinal chemistry. Herein we highlight the current advances in the synthesis of picolinamide-containing heterocyclic compounds as potent anticancer agents. In addition, briefly explore their structure-activity relationship studies for the inspiration of the innovation and development of more potent and effective drugs against various death-causing cancer diseases.

16.
Bioorg Chem ; 85: 325-336, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30658232

RESUMO

In the scientific field, nanotechnology has offered multipurpose and designated functional nanoparticles (NPs) for the development of applications in nano-medicine. This present review focuses on cutting edge of nanotechnology in biomedical applications as drug carries in cancer treatment. The nanotechnology overcomes several limitations of drug delivery systems used in distinct therapeutic approaches of cancer treatment. The serious effect of conventional chemotherapeutics by nonspecific targeting, the lack of solubility, and the inability of chemotherapeutics entry to cancer cells which, offers a great opportunity for nanotechnology to play significant roles in cancer biology. The selective delivery of nano-drugs to the targeted cancer cells by the programmed way and avoiding nonspecific interactions to the healthy cells. The present review focuses on the methods of improving the size, shape and characteristics of nanomaterials which can be exploited for cancer therapy. The successful designing of nanocarriers can be tailored for cancer treatment for upcoming future as nano-medicines.

17.
Eur J Med Chem ; 162: 364-377, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30453245

RESUMO

The multidrug-resistant Staphylococcus aureus (MRSA) is one of the most prevalent human pathogens involved in many minor to major disease burdens throughout the world. Inhibition of biofilm formation is an attractive strategy to treat diseases associated with MRSA infection. In the present investigation, a series of functional group diverse (hetero)aryl fluorosulfonyl analogs were designed, synthesized and tested as antibacterial agents against Staphylococcal spp., and as anti-biofilm candidates. Compounds 8, 15, and 67 were found to possess potent in vitro antibacterial activity among this class of sulfonyl fluorides (MIC = 0.818 ±â€¯0.42, 0.840 ±â€¯0.37 and 0.811 ±â€¯0.37 µg/mL respectively). The analogs 8, 15, 36, and 67 exhibited outstanding anti-biofilm properties compared to other available synthetic antibiotics. The efficacy of synthetic analogs displayed membrane-damaging effect and they are also validated by cellular content release assay. The insight physiological changes were explored by studying the intracellular redox activities through changing cyclic voltammetric (CV) method. The compounds 8, 15, 22, 32, 36, 51, and 67 were found to participate in the interfering in the electron transport chain (ETC) of MRSA. The analogs 8, 15, and 67 possess great potentiality for discovery and development of anti-staphylococcal drugs to treat the MRSA infections.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Fluoretos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Sulfonas/farmacologia , Biofilmes/efeitos dos fármacos , Complexo de Proteínas da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Simulação de Acoplamento Molecular , Oxirredução/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Ácidos Sulfínicos/farmacologia
18.
Eur J Med Chem ; 162: 679-734, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30496988

RESUMO

Sulfur (SVI) based moieties, especially, the sulfonyl or sulfonamide based analogues have showed a variety of pharmacological properties, and its derivatives propose a high degree of structural diversity that has established useful for the finding of new therapeutic agents. The developments of new less toxic, low cost and highly active sulfonamides containing analogues are hot research topics in medicinal chemistry. Currently, more than 150 FDA approved Sulfur (SVI)-based drugs are available in the market, and they are widely used to treat various types of diseases with therapeutic power. This comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents. We believe that, this review article is useful to inspire new ideas for structural design and developments of less toxic and powerful Sulfur (SVI) based drugs against the numerous death-causing diseases.


Assuntos
Descoberta de Drogas , Enxofre/uso terapêutico , Química Farmacêutica/métodos , Humanos , Ácidos Sulfínicos/uso terapêutico , Sulfonamidas/uso terapêutico , Terapêutica/métodos
19.
J Am Chem Soc ; 140(50): 17666-17673, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30481008

RESUMO

Direct synthesis of alkynes from inexpensive, abundant alcohols was achieved in high yields (greater than 40 examples, up to 95% yield) through a SO2F2-promoted dehydration and dehydrogenation process. This straightforward transformation of sp3-sp3 (C-C) bonds to sp-sp (C≡C) bonds requires only inexpensive and readily available reagents (no transition metals) under mild conditions. The crude alkynes are sufficiently free of impurities to permit direct use in further transformations, as illustrated by regioselective Huisgen alkyne-azide cycloaddition reactions with PhN3 to give 1,4-substituted 1,2,3-traiazoles (16 examples, up to 92% yield) and Sonogashira couplings (10 examples, up to 77% yield).

20.
ACS Comb Sci ; 20(12): 681-693, 2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30372025

RESUMO

Staphylococcus aureus is a bacterial pathogen that can cause significant disease burden and mortality by counteracting host defenses through producing virulence factors to survive the immune responses evoked by infection. This emerging drug-resistant pathogen has led to a decline in the efficacy of traditional antimicrobial therapy. To combat these threats, precision antimicrobial therapeutics have been created to target key virulence determinants of specific pathogens. Here we review the benefits of, progresses in, and roadblocks to the development of precision antimicrobial therapeutics using combinatorial chemistry.


Assuntos
Antibacterianos/farmacologia , Técnicas de Química Combinatória/métodos , Fatores Imunológicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Fatores de Virulência/imunologia , Antibacterianos/uso terapêutico , Descoberta de Drogas/métodos , Farmacorresistência Bacteriana , Humanos , Imunidade Inata , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Medicina de Precisão , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia
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