Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity.

Abstract:

:Protein tyrosine phosphatase 1B (PTP1B) as a key negative regulator of both insulin and leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated insulin receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake.

journal_name

Eur J Med Chem

authors

Liu P,Du Y,Song L,Shen J,Li Q

doi

10.1016/j.ejmech.2016.04.014

subject

Has Abstract

pub_date

2016-08-08 00:00:00

pages

27-33

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30296-3

journal_volume

118

pub_type

杂志文章
  • The computer-aided discovery of novel family of the 5-HT6 serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine.

    abstract::The work describes a discovery of new chemical family of potent ligands for the 5-HT6 serotonin receptors. During the search for new histamine H4 receptor antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active for the H4...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2017.04.033

    authors: Łażewska D,Kurczab R,Więcek M,Kamińska K,Satała G,Jastrzębska-Więsek M,Partyka A,Bojarski AJ,Wesołowska A,Kieć-Kononowicz K,Handzlik J

    更新日期:2017-07-28 00:00:00

  • Synthesis of novel 2-(1-adamantanylcarboxamido)thiophene derivatives. Selective cannabinoid type 2 (CB2) receptor agonists as potential agents for the treatment of skin inflammatory disease.

    abstract::A set of CB2R ligands, based on the thiophene scaffold, was synthesized and evaluated in in vitro assays. Compounds 8c-i, k, l, bearing the 3-carboxylate and 2-(adamantan-1-yl)carboxamido groups together with apolar alkyl/aryl substituents at 5-position or at 4- and 5-positions of the thiophene ring possess high CB2R ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2018.09.070

    authors: Mugnaini C,Rabbito A,Brizzi A,Palombi N,Petrosino S,Verde R,Di Marzo V,Ligresti A,Corelli F

    更新日期:2019-01-01 00:00:00

  • A novel series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones as selective monoamine oxidase (MAO) A inhibitors.

    abstract::A series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones (coumarins) have been synthesized and their inhibitory activity to human monoamine oxidase A (MAO A) and B (MAO B) determined. Incorporation of a basic amino function in the C3 position together with substitution at the C6 position produced novel coumar...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.11.035

    authors: Mattsson C,Svensson P,Sonesson C

    更新日期:2014-02-12 00:00:00

  • QSAR study of heparanase inhibitors activity using artificial neural networks and Levenberg-Marquardt algorithm.

    abstract::A linear and non-linear quantitative structure-activity relationship (QSAR) study is presented for modeling and predicting heparanase inhibitors' activity. A data set that consisted of 92 derivatives of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid, furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acids is u...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2007.04.014

    authors: Jalali-Heravi M,Asadollahi-Baboli M,Shahbazikhah P

    更新日期:2008-03-01 00:00:00

  • Umbelliferone aminoalkyl derivatives, a new class of squalene-hopene cyclase inhibitors.

    abstract::The synthesis is described of several aminoalkyl derivatives of coumarin, obtained in good yields under microwave or high-intensity ultrasound irradiation. These compounds proved uniformly active as inhibitors of squalene-hopene cyclase (SHC) from Alicyclobacillus acidocaldarius. Their design stemmed from our recent f...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2004.06.010

    authors: Cravotto G,Balliano G,Tagliapietra S,Palmisano G,Penoni A

    更新日期:2004-11-01 00:00:00

  • Synthesis, characterization and antiamoebic activity of new indole-3-carboxaldehyde thiosemicarbazones and their Pd(II) complexes.

    abstract::In continuation of our research on thiosemicarbazones and their metal complexes as antiamoebic agents, a new series of indole-3-carboxaldehyde thiosemicarbazones (TSC) 1-7 were prepared by condensing indole-3-carboxaldehyde with cycloalkylaminothiocarbonyl hydrazines. Their palladium(II) complexes of the [Pd(TSC)Cl2] ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2007.02.012

    authors: Husain K,Abid M,Azam A

    更新日期:2007-10-01 00:00:00

  • Novel inhibitors of nitric oxide synthase with antioxidant properties.

    abstract::We previously described a series of imidazole-based inhibitors substituted at N-1 with an arylethanone chain as interesting inhibitors of neuronal nitric oxide synthase (nNOS), endowed with good selectivity vs endothelial nitric oxide synthase (eNOS). As a follow up of these studies, several analogs characterized by t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2012.01.002

    authors: Salerno L,Modica MN,Romeo G,Pittalà V,Siracusa MA,Amato ME,Acquaviva R,Di Giacomo C,Sorrenti V

    更新日期:2012-03-01 00:00:00

  • Synthesis and antioxidant properties of some novel 5H-dibenz[b,f]azepine derivatives in different in vitro model systems.

    abstract::A series of 5H-dibenz[b,f]azepine containing different aminophenols and substituted aminophenols were synthesized. 3-chloro-1-(5H-dibenz[b,f]azepine-5yl)propan-1-one (2) was obtained by N-acylation of 5H-dibenz[b,f]azepine (1) with 3-chloro propionyl chloride. Further base condensation with different aminophenols and ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2009.09.016

    authors: Vijay Kumar H,Naik N

    更新日期:2010-01-01 00:00:00

  • Novel cis-selective and non-epimerisable C3 hydroxy azapodophyllotoxins targeting microtubules in cancer cells.

    abstract::Podophyllotoxin (PT) and its clinically used analogues are known to be powerful antitumour agents. These compounds contain a trans fused strained γ-lactone system, a feature that correlates to the process of epimerisation, whereby the trans γ-lactone system of ring D opens and converts to the more thermodynamically st...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.12.037

    authors: Kandil S,Wymant JM,Kariuki BM,Jones AT,McGuigan C,Westwell AD

    更新日期:2016-03-03 00:00:00

  • Synthesis, analgesic and anti-inflammatory activities evaluation of some bi-, tri- and tetracyclic condensed pyrimidines.

    abstract::Novel series of bicyclic pyrrolo[1,2-c]pyrimidines 3a-g, 5, 6a, b, and 7a, b, tricyclic pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines 8a-c, 9a-g, 13a-c, 17, 18a, b, 19, 20a,b and 21 and tetracyclic condensed pyrimidines 14, 22 and 23 were synthesized through different chemical reactions. Structures of all synthesized pyrim...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2009.06.028

    authors: Amin KM,Hanna MM,Abo-Youssef HE,George RF

    更新日期:2009-11-01 00:00:00

  • Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis.

    abstract::Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.05.035

    authors: Michailidou M,Giannouli V,Kotsikoris V,Papadodima O,Kontogianni G,Kostakis IK,Lougiakis N,Chatziioannou A,Kolisis FN,Marakos P,Pouli N,Loutrari H

    更新日期:2016-10-04 00:00:00

  • Heterodimeric Rifampicin-Tobramycin conjugates break intrinsic resistance of Pseudomonas aeruginosa to doxycycline and chloramphenicol in vitro and in a Galleria mellonella in vivo model.

    abstract::Intrinsic resistance in Pseudomonas aeruginosa, defined by chromosomally encoded low outer membrane permeability and constitutively over-expressed efflux pumps, is a major reason why the pathogen is refractory to many antibiotics. Herein, we report that heterodimeric rifampicin-tobramycin conjugates break this intrins...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2019.04.034

    authors: Idowu T,Arthur G,Zhanel GG,Schweizer F

    更新日期:2019-07-15 00:00:00

  • Design, synthesis and evaluation of diarylpiperazine derivatives as potent anti-tubercular agents.

    abstract::Molecular hybridization is an emerging approach to design novel ligands by combination of two or more pharmacophoric subunits of known bioactive compounds. In the present study, we have designed a novel series of diarylpiperazine analogues, synthesized, characterized using FTIR, (1)H NMR, Mass, Elemental analysis and ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.10.024

    authors: Penta A,Franzblau S,Wan B,Murugesan S

    更新日期:2015-11-13 00:00:00

  • Site-directed mutagenesis provides insights into the selective binding of trityl derivatives to Plasmodium falciparum dUTPase.

    abstract::We have previously identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which selectively inhibit Plasmodium falciparum deoxyuridine triphosphate nucleotidohydrolase (PfdUTPase) compared to the human enzyme. The crystal structure of PfdUTPase in complex with one of th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2011.04.052

    authors: Recio E,Musso-Buendía A,Vidal AE,Ruda GF,Kasinathan G,Nguyen C,Ruiz-Pérez LM,Gilbert IH,González-Pacanowska D

    更新日期:2011-08-01 00:00:00

  • Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line.

    abstract::Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2018.07.003

    authors: Zaki I,Abdelhameid MK,El-Deen IM,Abdel Wahab AHA,Ashmawy AM,Mohamed KO

    更新日期:2018-08-05 00:00:00

  • Novel hydrazone moiety-bearing aminopyrimidines as selective inhibitors of epidermal growth factor receptor T790M mutant.

    abstract::The epidermal growth factor receptor (EGFR) T790M mutant is found in approximately 50% of clinically acquired resistance to gefitinib among patients with non-small cell lung cancer (NSCLC). Here, a series of novel aminopyrimidines bearing a hydrazone moiety were identified as potent and selective EGFR inhibitors. Comp...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.09.031

    authors: Qin M,Wang T,Xu B,Ma Z,Jiang N,Xie H,Gong P,Zhao Y

    更新日期:2015-11-02 00:00:00

  • Synergistic induction of apoptosis in resistant head and neck carcinoma and leukemia by alkoxyamide-based histone deacetylase inhibitors.

    abstract::Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization o...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2020.113095

    authors: Alves Avelar LA,Schrenk C,Sönnichsen M,Hamacher A,Hansen FK,Schliehe-Diecks J,Borkhardt A,Bhatia S,Kassack MU,Kurz T

    更新日期:2021-02-05 00:00:00

  • Recent advances in small molecule based cancer immunotherapy.

    abstract::Immunotherapy has been increasingly utilized for the treatment of cancer. Currently available cancer immunotherapies mainly involve the use of antibodies, which have advantages in terms of pharmacodynamics such as efficacy and specificity, however, they exhibit disadvantages in regard to the pharmacokinetics including...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.ejmech.2018.08.028

    authors: Cheng B,Yuan WE,Su J,Liu Y,Chen J

    更新日期:2018-09-05 00:00:00

  • Inhibitors of the kynurenine pathway.

    abstract::Strokes (intracranial thomboses or haemorrhaging) cause death and disability, but effective treatments are lacking. The metabolism of tryptophan leads to the generation of quinolinic acid, an agonist potentially neurotoxic at glutamate receptors, and kynurenic acid, an antagonist at the same population of receptors. T...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/s0223-5234(00)00121-5

    authors: Stone TW

    更新日期:2000-02-01 00:00:00

  • Design, synthesis and high antitumor potential of new unsymmetrical bisacridine derivatives towards human solid tumors, specifically pancreatic cancers and their unique ability to stabilize DNA G-quadruplexes.

    abstract::New promising unsymmetrical bisacridine derivatives (UAs), have been developed. Three groups including 36 compounds were synthesized by the condensation of 4-nitro or 4-methylacridinone, imidazoacridinone and triazoloacridinone derivatives with 1-nitroacridine compounds linked with an aminoalkyl chain. Cytotoxicity sc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2020.112599

    authors: Paluszkiewicz E,Horowska B,Borowa-Mazgaj B,Peszyńska-Sularz G,Paradziej-Łukowicz J,Augustin E,Konopa J,Mazerska Z

    更新日期:2020-10-15 00:00:00

  • A phosphonamidate containing aromatic N-terminal amino group as inhibitor of leucine aminopeptidase-design, synthesis and stability.

    abstract::Fully deprotected phosphonamidate dipeptides, predicted as effective inhibitors of cytosolic leucine aminopeptidase, showed unexpected instability in water solution at pH below 12. Their hydrolysis rate was strictly correlated with basicity of the N-terminal amino group. To improve this feature a phosphonamidate analo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2006.03.023

    authors: Mucha A,Kunert A,Grembecka J,Pawełczak M,Kafarski P

    更新日期:2006-06-01 00:00:00

  • Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives.

    abstract::We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analy...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2007.12.004

    authors: Khan SA,Kumar P,Joshi R,Iqbal PF,Saleem K

    更新日期:2008-09-01 00:00:00

  • The synthesis and biological evaluation of new DNA-directed alkylating agents, phenyl N-mustard-4-anilinoquinoline conjugates containing a urea linker.

    abstract::We synthesized a series of phenyl N-mustard-4-anilinoquinoline conjugates to study their antitumorigenic effects. These agents were prepared by the condensation of 4-[N,N-bis(2-chloroethyl)amino]phenyl isocyanate with 6-amino-4-methylamino or 4-anilinoquinolines. The structure-activity relationship (SAR) studies revea...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.06.066

    authors: Marvania B,Kakadiya R,Christian W,Chen TL,Wu MH,Suman S,Tala K,Lee TC,Shah A,Su TL

    更新日期:2014-08-18 00:00:00

  • Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6-diphenyl-1,2,4-triazin-3(2H)-one derivatives bearing 5-substituted 1,3,4-oxadiazole as potential anti-inflammatory and analgesic agents.

    abstract::A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in ac...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.06.020

    authors: Banerjee AG,Das N,Shengule SA,Srivastava RS,Shrivastava SK

    更新日期:2015-08-28 00:00:00

  • Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare.

    abstract::In our continued efforts to improve the potential utility of the α-methylene-γ-lactone scaffold, 62 new and 59 known natural α-methylenelactam analogues including α-methylene-γ-lactams, α-arylidene-γ and δ-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the α-methylenelactone s...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2017.02.050

    authors: Delong W,Lanying W,Yongling W,Shuang S,Juntao F,Xing Z

    更新日期:2017-04-21 00:00:00

  • Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction.

    abstract::Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tum...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.10.031

    authors: Huang KB,Chen ZF,Liu YC,Wang M,Wei JH,Xie XL,Zhang JL,Hu K,Liang H

    更新日期:2013-01-01 00:00:00

  • Synthesis and biological evaluation of 2-phenylthiazole-4-carboxamide derivatives as anticancer agents.

    abstract::A series of substituted 2-phenylthiazole-4-carboxamide derivatives were synthesized as potential cytotoxic agents and evaluated against three human cancer cell lines including T47D (Breast cancer), Caco-2 (Colorectal cancer) and HT-29 (Colon cancer). The SAR of the arylacetamido pendent connected to the para-position ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2010.08.063

    authors: Aliabadi A,Shamsa F,Ostad SN,Emami S,Shafiee A,Davoodi J,Foroumadi A

    更新日期:2010-11-01 00:00:00

  • Recent methodologies toward the synthesis of valdecoxib: a potential 3,4-diarylisoxazolyl COX-II inhibitor.

    abstract::Non-steroidal anti-inflammatory drugs are widely used therapeutic agents in the treatment of inflammation, pain and fever. Cyclooxygenase catalyzes the initial step of biotransformation of arachidonic acid to prostanoids, and exist as three distinct isozymes; COX-I, COX-II and COX-III. Selective COX-II inhibitors are ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.ejmech.2010.07.045

    authors: Dadiboyena S,Nefzi A

    更新日期:2010-11-01 00:00:00

  • Synthesis, antiproliferative activity and inhibition of tubulin polymerization by anthracenone-based oxime derivatives.

    abstract::A series of anthracenone-based oxime ethers and -esters were synthesized in order to evaluate their antiproliferative activity. Several investigated compounds displayed strong antiproliferative activity against K562 leukemia cells and proved to be strong inhibitors of tubulin polymerization. In this context, anthracen...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2010.04.019

    authors: Surkau G,Böhm KJ,Müller K,Prinz H

    更新日期:2010-08-01 00:00:00

  • Structure-activity relationships study of 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives as novel non-nucleoside anti-hepatitis B virus agents.

    abstract::A series of novel 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives were synthesized and evaluated for anti-hepatitis B virus (anti-HBV) activities in vitro to explore their structure-activity relationships (SARs). Most of the synthesized compounds possessed potent anti-HBV activity, of whi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2010.11.019

    authors: Guo RH,Zhang Q,Ma YB,Luo J,Geng CA,Wang LJ,Zhang XM,Zhou J,Jiang ZY,Chen JJ

    更新日期:2011-01-01 00:00:00