当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.

Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.

Abstract：

:Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487 μM against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IRβ, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Li XQ,Xu Q,Luo J,Wang LJ,Jiang B,Zhang RS,Shi DY

doi

10.1016/j.ejmech.2017.05.007

subject

Has Abstract

pub_date

2017-08-18 00:00:00

pages

348-359

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30368-9

journal_volume

136

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Benzofuran derivatives as anticancer inhibitors of mTOR signaling.

    abstract：:A series of 32 derivatives and isosteres of the mTOR inhibitor 2 were synthesized and compared for their cytotoxicity in radioresistant SQ20B cancer cell line. Several of these compounds, in particular 30b, were significantly more cytotoxic than 2. Importantly, 30b was shown to block both mTORC1 and Akt signaling, sug...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.05.014

    authors： Salomé C,Ribeiro N,Chavagnan T,Thuaud F,Serova M,de Gramont A,Faivre S,Raymond E,Désaubry L

    更新日期：2014-06-23 00:00:00

  • New isoxazolidinone and 3,4-dehydro-β-proline derivatives as antibacterial agents and MAO-inhibitors: A complex balance between two activities.

    abstract：:Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.09.007

    authors： Ferrazzano L,Viola A,Lonati E,Bulbarelli A,Musumeci R,Cocuzza C,Lombardo M,Tolomelli A

    更新日期：2016-11-29 00:00:00

  • High affinity ligands and potent antagonists for the α1D-adrenergic receptor. Novel 3,8-disubstituted [1]benzothieno[3,2-d]pyrimidine derivatives.

    abstract：:A new series of high affinity ligands and antagonists for the α1D-adrenergic receptor (AR) has been discovered. New molecules present a [1]benzothieno[3,2-d]pyrimidin-2,4(1H,3H)-dione or a [1]benzothieno[3,2-d]pyrimidin-4(3H)-one scaffold and bear a 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl moiety in the 3-position a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.06.057

    authors： Romeo G,Salerno L,Pittalà V,Modica MN,Siracusa MA,Materia L,Buccioni M,Marucci G,Minneman KP

    更新日期：2014-08-18 00:00:00

  • Design and synthesis of novel xanthone-triazole derivatives as potential antidiabetic agents: α-Glucosidase inhibition and glucose uptake promotion.

    abstract：:Inhibiting the decomposition of carbohydrates into glucose or promoting glucose conversion is considered to be an effective treatment for type 2 diabetes. Herein, a series of novel xanthone-triazole derivatives were designed, synthesized, and their α-glucosidase inhibitory activities and glucose uptake in HepG2 cells ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.05.045

    authors： Ye GJ,Lan T,Huang ZX,Cheng XN,Cai CY,Ding SM,Xie ML,Wang B

    更新日期：2019-09-01 00:00:00

  • Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors.

    abstract：:The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have been carried out to ratio...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.12.020

    authors： Pinto A,Conti P,Grazioso G,Tamborini L,Madsen U,Nielsen B,De Micheli C

    更新日期：2011-02-01 00:00:00

  • Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents.

    abstract：:The efficient synthesis of novel azetidin-2-ones 6 has been established. Thus, condensation of 5-[(2-methyl-1H-benzimidazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine 4 with various aromatic aldehydes afforded 5-[(2-methyl-1H-benzimidazol-1-yl)methyl]-N-[(substituted) phenylmethylidene]-1,3,4-thiadiazol-2-amine 5 which on ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.01.022

    authors： Ansari KF,Lal C

    更新日期：2009-05-01 00:00:00

  • Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer's disease.

    abstract：:New benzofuranylthiazole derivatives containing the aryl-urea moiety were synthesized and evaluated in vitro as dual acetylcholinesterase (AChE)-butyrylcholinesterase (BuChE) inhibitors. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized com...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.07.005

    authors： Kurt BZ,Gazioglu I,Basile L,Sonmez F,Ginex T,Kucukislamoglu M,Guccione S

    更新日期：2015-09-18 00:00:00

  • Discovery of novel series of 2-substituted benzo[d]oxazol-5-amine derivatives as multi-target directed ligands for the treatment of Alzheimer's disease.

    abstract：:Alzheimer's disease (AD) is associated with multifactorial neuropathological conditions, which include cholinergic deficit, amyloid-beta plaques formation, loss of neuronal plasticity and neuronal death. Treating such multifactorial conditions with a single target directed approach is considered to be inadequate. Acco...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.111613

    authors： Gutti G,Kakarla R,Kumar D,Beohar M,Ganeshpurkar A,Kumar A,Krishnamurthy S,Singh SK

    更新日期：2019-11-15 00:00:00

  • A pentanoic acid derivative targeting matrix metalloproteinase-2 (MMP-2) induces apoptosis in a chronic myeloid leukemia cell line.

    abstract：:Depending on our previous observations, some compounds of pentanoic acid were designed and synthesized. Characterization of the synthesized compounds was done by mass, NMR and IR spectroscopy as well as elemental analysis. Among the synthesized molecules, (2S)-5-oxo-2-[(nitrobenzene-4-yl sulfonyl) amino]-5-(pentylamin...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.09.052

    authors： Mukherjee A,Adhikari N,Jha T

    更新日期：2017-12-01 00:00:00

  • Design, synthesis and antibacterial evaluation of novel pleuromutilin derivatives possessing piperazine linker.

    abstract：:A series of pleuromutilin derivatives bearing piperazine ring have been reported. The in vitro antibacterial activities of the synthetic derivatives against MRSA (ATCC 43300), Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212), Enterococcus faecium (ATCC35667) and Escherichia coli (ATCC25922) were ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.01.004

    authors： Gao ML,Zeng J,Fang X,Luo J,Jin Z,Liu YH,Tang YZ

    更新日期：2017-02-15 00:00:00

  • Synthesis and antimicrobial activity of some novel dicationic sulphonophanes.

    abstract：:The synthesis of some novel imidazole-based dicationic sulfonophanes incorporating various spacer units is described. All the sulphonophanes exhibit good antibacterial and antifungal activity against five bacterial strains Bacillus subtilis, Staphylococcus aureus, Vibrio cholera, Escherichia coli, Proteus vulgaris and...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.03.063

    authors： Rajakumar P,Satheeshkumar C,Mohanraj G,Mathivanan N

    更新日期：2011-07-01 00:00:00

  • Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents.

    abstract：:A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4'-Indolyl and 6'-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative acti...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.04.065

    authors： Lai MJ,Chang JY,Lee HY,Kuo CC,Lin MH,Hsieh HP,Chang CY,Wu JS,Wu SY,Shey KS,Liou JP

    更新日期：2011-09-01 00:00:00

  • QSAR study of 4-phenylpiperidine derivatives as mu opioid agonists by neural network method.

    abstract：:A nonlinear QSAR study was conducted on a series of 4-phenylpiperidine derivatives (4PPs) acting as mu opioid agonists by three-layer back-propagation neural network (NN) method. At first a variety of molecular descriptors were calculated and then selected with two-stage least squares combining partial least squares (...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.10.017

    authors： Wang XH,Tang Y,Xie Q,Qiu ZB

    更新日期：2006-02-01 00:00:00

  • Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity.

    abstract：:Xanthine oxidase (XO), a versatile metalloflavoprotein enzyme, catalyzes the oxidative hydroxylation of hypoxanthine and xanthine to uric acid in purine catabolism while simultaneously producing reactive oxygen species. Both lead to the gout-causing hyperuricemia and oxidative damage of the tissues where overactivity ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2017.04.031

    authors： Šmelcerović A,Tomović K,Šmelcerović Ž,Petronijević Ž,Kocić G,Tomašič T,Jakopin Ž,Anderluh M

    更新日期：2017-07-28 00:00:00

  • Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase.

    abstract：:In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.07.005

    authors： Kashif M,Chacón-Vargas KF,López-Cedillo JC,Nogueda-Torres B,Paz-González AD,Ramírez-Moreno E,Agusti R,Uhrig ML,Reyes-Arellano A,Peralta-Cruz J,Ashfaq M,Rivera G

    更新日期：2018-08-05 00:00:00

  • Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists.

    abstract：:Cannabinoids are potentially useful for the treatment of several diseases. In the present work, we report the syntheses and biological evaluations of 1,2,4-triazolone derivatives designed using a combined approach of scaffold hopping and pharmacophore-oriented method. These compounds exhibited interesting antagonistic...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.12.018

    authors： Han S,Zhang FF,Xie X,Chen JZ

    更新日期：2014-03-03 00:00:00

  • Optimization of substituted imidazobenzodiazepines as novel asthma treatments.

    abstract：:We describe the synthesis of analogs of XHE-III-74, a selective α4β3γ2 GABAAR ligand, shown to relax airway smooth muscle ex vivo and reduce airway hyperresponsiveness in a murine asthma model. To improve properties of this compound as an asthma therapeutic, a series of analogs with a deuterated methoxy group in place...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.11.045

    authors： Jahan R,Stephen MR,Forkuo GS,Kodali R,Guthrie ML,Nieman AN,Yuan NY,Zahn NM,Poe MM,Li G,Yu OB,Yocum GT,Emala CW,Stafford DC,Cook JM,Arnold LA

    更新日期：2017-01-27 00:00:00

  • 4-Aminoquinoline derived antimalarials: synthesis, antiplasmodial activity and heme polymerization inhibition studies.

    abstract：:A new series of 4-aminoquinoline derivatives have been synthesized and found to be active against both susceptible and resistant strains of Plasmodium falciparum in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl-thiourea (7) exhibited superior in vitro activity against resistant strains of P....

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.07.068

    authors： Solomon VR,Haq W,Smilkstein M,Srivastava K,Puri SK,Katti SB

    更新日期：2010-11-01 00:00:00

  • Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel cyano- and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes, thieno-benzofurans, benzo-dithiophenes and their acyclic precursors.

    abstract：:As a part of the research on the improvement of an alternative to conventional photodynamic therapy by light-induced formation of intercalators, we synthesized a series of novel heterocyclic compounds and their acyclic precursors. We now report details about their synthesis/characterization in respect to their potenti...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.03.012

    authors： Starcević K,Kralj M,Piantanida I,Suman L,Pavelić K,Karminski-Zamola G

    更新日期：2006-08-01 00:00:00

  • Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents.

    abstract：:Several naphthalimide polyamine conjugates were synthesized and evaluated for in vitro cytotoxicity against human leukemia K562, murine melanoma B16, Chinese hamster ovary CHO cell lines. Both triamine moieties and the length of spacers were crucial in elevating the potency of 1,8-naphthalimide. The typical compounds ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.02.044

    authors： Tian ZY,Xie SQ,Du YW,Ma YF,Zhao J,Gao WY,Wang CJ

    更新日期：2009-01-01 00:00:00

  • Novel deoxyvasicinone derivatives as potent multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

    abstract：:A series of multitarget ligands was designed by introducing several structurally diverse aminoacetamide groups at position 6 of the deoxyvasicinone group, with the aim of obtaining novel multifunctional anti-Alzheimer's disease agents using deoxyvasicinone as the substrate. In vitro studies showed that almost all of t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.09.008

    authors： Ma F,Du H

    更新日期：2017-11-10 00:00:00

  • Modulating hydrogen-bond basicity within the context of protein-ligand binding: A case study with thrombin inhibitors that reveals a dominating role for desolvation.

    abstract：:Understanding subtle aspects of hydrogen bonding is a challenging but crucial task to improve our ability to design ligands with high affinity for protein hosts. To gain a deeper understanding of these aspects, we investigated a series of thrombin inhibitors in which the basicity of the ligand's group that accepts an ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.09.038

    authors： Nasief NN,Said AM,Hangauer D

    更新日期：2017-01-05 00:00:00

  • 2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer's disease.

    abstract：:Alzheimer's disease is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of "one drug, one target" has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that ca...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.113112

    authors： Mezeiova E,Janockova J,Andrys R,Soukup O,Kobrlova T,Muckova L,Pejchal J,Simunkova M,Handl J,Micankova P,Capek J,Rousar T,Hrabinova M,Nepovimova E,Marco-Contelles JL,Valko M,Korabecny J

    更新日期：2021-02-05 00:00:00

  • Structural modifications at the 6-position of thieno[2,3-d]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia.

    abstract：:Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 in...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.05.022

    authors： Kim H,Lee C,Yang JS,Choi S,Park CH,Kang JS,Oh SJ,Yun J,Kim MH,Han G

    更新日期：2016-09-14 00:00:00

  • Repurposed drug candidates for antituberculosis therapy.

    abstract：:Antibiotics have been a key part of clinical treatments for more than 70 years. Long-term use of antimicrobial treatments has led to the development of severe bacterial resistance, which has become increasingly serious due to antibiotic abuse, resulting in the treatment of bacterial infections becoming challenging. Th...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.112175

    authors： An Q,Li C,Chen Y,Deng Y,Yang T,Luo Y

    更新日期：2020-04-15 00:00:00

  • Pharmaceutical salts and cocrystals involving amino acids: a brief structural overview of the state-of-art.

    abstract：:Salification of new drug substances in order to improve physico-chemical or solid-state properties (e.g. dissolution rate or solubility, appropriate workup process, storage for further industrial and marketing development) is a well-accepted procedure. Amino acids, like aspartic acid, lysine or arginine take a great p...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2013.11.045

    authors： Tilborg A,Norberg B,Wouters J

    更新日期：2014-03-03 00:00:00

  • Recent advances of analogues of curcumin for treatment of cancer.

    abstract：:Curcumin (CU), an edible natural pigment from Curcuma Longa, has demonstrated extensive anti-tumor effect in vivo and in vitro. With the property of reversing drug resistance and low toxicity, CU has been considered to develop a new adjuvant chemotherapy protocol of cancer. However, the poor stability, solubility, in ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2019.07.034

    authors： Zhao S,Pi C,Ye Y,Zhao L,Wei Y

    更新日期：2019-10-15 00:00:00

  • Synthesis and comparative photodynamic properties of two isosteric alkyl substituted zinc(II) phthalocyanines.

    abstract：:The synthesis and photophysical parameters of two novel isosteric cationic zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.09.014

    authors： Gauna GA,Marino J,García Vior MC,Roguin LP,Awruch J

    更新日期：2011-11-01 00:00:00

  • Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4.

    abstract：:It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine com...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112706

    authors： Zhang G,Wang M,Zhao J,Wang Y,Zhu M,Wang J,Cen S,Wang Y

    更新日期：2020-11-15 00:00:00

  • New synthesis of 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, nanomolar inhibitors of glycogen phosphorylase.

    abstract：:O-Perbenzoylated 5-(β-D-glucopyranosyl)tetrazole was reacted with N-benzyl carboximidoyl chlorides to give the corresponding 4-benzyl-3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles. Removal of the O-benzoyl and N-benzyl protecting groups by base catalysed transesterification and catalytic hydrogenation, respecti...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.02.041

    authors： Kun S,Bokor É,Varga G,Szőcs B,Páhi A,Czifrák K,Tóth M,Juhász L,Docsa T,Gergely P,Somsák L

    更新日期：2014-04-09 00:00:00