当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies.

Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies.

Abstract：

:We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as α7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for α7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2.3 and 3 nM respectively). They exhibited a strict selectivity toward the α4β2 nicotinic receptor (up to 1 μM) but interacted with the 5HT3 receptors with Ki around 3 nM. Synthesis, SAR studies and a full description of the derivatives are reported.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Ouach A,Pin F,Bertrand E,Vercouillie J,Gulhan Z,Mothes C,Deloye JB,Guilloteau D,Suzenet F,Chalon S,Routier S

doi

10.1016/j.ejmech.2015.11.001

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

153-64

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)30338-X

journal_volume

107

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity.

    abstract：:Thorough simplification of vinca alkaloids based on pharmacophore similarity has been conducted. A concise process for the syntheses of target compounds was successfully developed with yields from poor to excellent (19-98%). Cell growth inhibitory activities of these synthesized compounds were evaluated in five cancer...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.04.057

    authors： Zheng J,Deng L,Chen M,Xiao X,Xiao S,Guo C,Xiao G,Bai L,Ye W,Zhang D,Chen H

    更新日期：2013-07-01 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

  • 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

  • Correlation of calculated molecular orbital energies of some phenothiazine compounds with MDR reversal properties.

    abstract：:Molecular orbital energies of energetically minimized series of extended aromatic and aminoalkyl side chain substituted phenothiazine compounds have been considered with respect to charge transfer (CT) binding properties to P-glycoprotein (P-gp) amino acids of the first P-gp loop. A dependency of decreasing energies o...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.11.011

    authors： Hilgeroth A,Molnár A,Molnár J,Voigt B

    更新日期：2006-04-01 00:00:00

  • Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway.

    abstract：:The structure-specific ERCC1-XPF endonuclease is essential for repairing bulky DNA lesions and helix distortions induced by UV radiation, which forms cyclobutane pyrimidine dimers (CPDs), or chemicals that crosslink DNA strands such as cyclophosphamide and platinum-based chemotherapeutic agents. Inhibition of the ERCC...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112658

    authors： Elmenoufy AH,Gentile F,Jay D,Karimi-Busheri F,Yang X,Soueidan OM,Mani RS,Ciniero G,Tuszynski JA,Weinfeld M,West FG

    更新日期：2020-10-15 00:00:00

  • 6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and antiangiogenic activity.

    abstract：:A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.03.045

    authors： Kim DG,Kang Y,Lee H,Lee EK,Nam TG,Kim JA,Jeong BS

    更新日期：2014-05-06 00:00:00

  • Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid derivatives as DNMT and HDAC inhibitors.

    abstract：:DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of the...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.04.017

    authors： Yuan Z,Sun Q,Li D,Miao S,Chen S,Song L,Gao C,Chen Y,Tan C,Jiang Y

    更新日期：2017-07-07 00:00:00

  • Database mining applied to central nervous system (CNS) activity.

    abstract：:A data set of 389 compounds, active in the central nervous system (CNS) and divided into eight classes according to the receptor type, was extracted from the RBI database and analyzed by Self-Organizing Maps (SOM), also known as Kohonen Artificial Neural Networks. This method gives a 2D representation of the distribut...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01233-8

    authors： Pintore M,Taboureau O,Ros F,Chrétien JR

    更新日期：2001-04-01 00:00:00

  • African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase.

    abstract：:African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enz...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.09.067

    authors： West RA,O'Doherty OG,Askwith T,Atack J,Beswick P,Laverick J,Paradowski M,Pennicott LE,Rao SPS,Williams G,Ward SE

    更新日期：2017-12-01 00:00:00

  • Novel ruthenium complexes ligated with 4-anilinoquinazoline derivatives: synthesis, characterisation and preliminary evaluation of biological activity.

    abstract：:The ruthenium DMSO complexes cis-Ru(II)C12(DMSO)4 and [(DMSO)2H][trans-Ru(III)Cl4(DMSO)2] reacted with 4-(3'-chloro-4'-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline (L1), 4-(3'-chloro-4'-fluoroanilino)-6-(2-(1H-imidazol-1-yl)ethoxy)-7-methoxy quinazoline (L2), N-(benzo[d]imidazol-4-yl)-6,7-dimeth...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.02.062

    authors： Ji L,Zheng W,Lin Y,Wang X,Lü S,Hao X,Luo Q,Li X,Yang L,Wang F

    更新日期：2014-04-22 00:00:00

  • Design of antineoplastic agents based on the '2-phenylnaphthalene-type' structural pattern--synthesis and biological activity studies of 11H-indolo[3.2-c]quinoline derivatives.

    abstract：:Designed as a new group of planar molecule containing the proposed 2-phenylnaphthalene-type structure, a number of 11H-indolo[3.2-c]quinoline derivatives were synthesized and evaluated biologically. Several compounds were found to possess cytotoxic activity against the growth of human promyelocytic leukemia cells (HL-...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(02)01420-4

    authors： He L,Chang HX,Chou TC,Savaraj N,Cheng CC

    更新日期：2003-01-01 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

  • Phenylpropiophenone derivatives as potential anticancer agents: synthesis, biological evaluation and quantitative structure-activity relationship study.

    abstract：:Series of twelve chalcone and propafenone derivatives has been synthesized and evaluated for anticancer activities against HeLa, Fem-X, PC-3, MCF-7, LS174 and K562 cell lines. The 2D-QSAR and 3D-QSAR studies were performed for all compounds with cytotoxic activities against each cancer cell line. Partial least squares...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.02.013

    authors： Ivković BM,Nikolic K,Ilić BB,Žižak ŽS,Novaković RB,Čudina OA,Vladimirov SM

    更新日期：2013-05-01 00:00:00

  • N1-Alkylated 3,4-dihydropyrimidine-2(1H)-ones: Convenient one-pot selective synthesis and evaluation of their calcium channel blocking activity.

    abstract：:It has been found that selective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones can be achieved under solvent-less, mild phase transfer catalytic (PTC) conditions with tetrabutylammonium hydrogen sulfate and 50% aqueous NaOH as the catalyst and base, respectively. The procedure is tolerant to substitutional variati...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.10.002

    authors： Singh K,Arora D,Poremsky E,Lowery J,Moreland RS

    更新日期：2009-05-01 00:00:00

  • Synthesis and in vitro Trichomonacidal activities of some new dialkylperoxides and 1,2,4-trioxanes.

    abstract：:Two series of three trioxanes and 18 disubstituted peroxides were synthesised and evaluated for their in vitro trichomonacidal activity against Trichomonas vaginalis. The most active compound, 2-methylprop-2-yl 2-methoxyeth-1-yl peroxide exhibited an IC(50) value of 1.0+/-0.2 microM whereas other dialkyl peroxides had...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01278-8

    authors： Camuzat-Dedenis B,Provot O,Cointeaux L,Peyrou V,Berrien JF,Bories C,Loiseau PM,Mayrargue J

    更新日期：2001-10-01 00:00:00

  • Dependence of fungistatic activity of 2, 4-dihydroxythiobenzanilideson the structure and lipophilic nature of the compounds.

    abstract：:The quantitative dependencies of in vitro fungistatic action on the physico-chemical parameters connected with the structure of 2, 4-dihydroxythiobenzanilides were investigated. It was stated that the action of these compounds depends on lipophilicity determined by substitution of the N-aryl moiety and on electron pro...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(00)00136-7

    authors： Matysiak J,Niewiadomy A,Macik-Niewiadomy G,Kornillowicz T

    更新日期：2000-04-01 00:00:00

  • ROS-responsive and multifunctional anti-Alzheimer prodrugs: Tacrine-ibuprofen hybrids via a phenyl boronate linker.

    abstract：:Current drugs available in clinic for Alzheimer's disease (AD) treatment can only alleviate disease symptoms without clearly curing or delaying the process of AD. And some AD drugs failed in Phase III clinical trials are only focused on targeting amyloid-β (Aβ). Therefore, an alternative strategy in AD drug design is ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112997

    authors： Liu Z,Zhang B,Xia S,Fang L,Gou S

    更新日期：2020-11-06 00:00:00

  • Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.

    abstract：:Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with bi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.07.109

    authors： Gul R,Rauf MK,Badshah A,Azam SS,Tahir MN,Khan A

    更新日期：2014-10-06 00:00:00

  • Steroidal N-Sulfonylimidates: Synthesis and biological evaluation in breast cancer cells.

    abstract：:Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-ethynyl steroids via Cu-catalyzed azide-alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and E...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.06.048

    authors： Volkova YA,Kozlov AS,Kolokolova MK,Uvarov DY,Gorbatov SA,Andreeva OE,Scherbakov AM,Zavarzin IV

    更新日期：2019-10-01 00:00:00

  • Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives.

    abstract：:A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluate...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.12.050

    authors： Teng YO,Zhao HY,Wang J,Liu H,Gao ML,Zhou Y,Han KL,Fan ZC,Zhang YM,Sun H,Yu P

    更新日期：2016-04-13 00:00:00

  • Polycyclic propargylamine and acetylene derivatives as multifunctional neuroprotective agents.

    abstract：:The aim of this study was to design drug-like molecules with multiple neuroprotective mechanisms which would ultimately inhibit N-methyl-D-aspartate (NMDA) receptors, block L-type voltage gated calcium channels (VGCC) and inhibit apoptotic processes as well as the monoamine oxidase-B (MAO-B) enzyme in the central nerv...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.04.039

    authors： Zindo FT,Barber QR,Joubert J,Bergh JJ,Petzer JP,Malan SF

    更新日期：2014-06-10 00:00:00

  • Synthesis, cytotoxicity and structure-activity relationship of indolizinoquinolinedione derivatives as DNA topoisomerase IB catalytic inhibitors.

    abstract：:Our previous studies reveal that indolizinoquinolinedione scaffold is a base to develop novel DNA topoisomerase IB (TOP1) catalytic inhibitors. In this work, twenty-three novel indolizinoquinolinedione derivatives were synthesized. TOP1-mediated relaxation, nicking and unwinding assays revealed that three fluorinated ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.04.040

    authors： Yu Q,Yang H,Zhu TW,Yu LM,Chen JW,Gu LQ,Huang ZS,An LK

    更新日期：2018-05-25 00:00:00

  • Thioether-based 2-aminobenzamide derivatives: Novel HDAC inhibitors with potent in vitro and in vivo antitumor activity.

    abstract：:Previously, we focused on a series of 2-aminobenzamide-based histone deacetylase (HDAC) inhibitors, compound 9 of which displayed potent HDAC inhibitory activity against HDAC1 and HDAC2, and moderate anti-proliferative activity against several cancer cell lines. In the current study, we have designed and synthesized a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.05.007

    authors： Yun F,Cheng C,Ullah S,He J,Zahi MR,Yuan Q

    更新日期：2019-08-15 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

  • Design, synthesis and pharmacological evaluation of N4,N6-disubstituted pyrimidine-4,6-diamine derivatives as potent EGFR inhibitors in non-small cell lung cancer.

    abstract：:A novel series of 4, 6-disubstituted pyrimidines derivatives were designed, synthesized, and evaluated as epidermal growth factor receptor (EGFR) inhibitors for non-small cell lung cancer(NSCLC). 4, 6-disubstituted pyrimidines as core structure was utilized to substitute the lead structure AZD3759 of the quinazoline b...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.08.031

    authors： Zhang Y,Lv H,Luo L,Xu Y,Pan Y,Wang Y,Lin H,Xiong J,Guo P,Zhang J,Li X,Ye F

    更新日期：2018-09-05 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

  • Inhibitors of phosphopantetheine adenylyltransferase.

    abstract：:Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in Coenzyme A biosynthesis. Because bacterial PPAT and mammalian PPAT are dissimilar, this enzyme is an attractive antibacterial target. Based on the structure of the substrate, 4-phosphopantetheine, a dipeptide library was designed, synthesised and ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(03)00047-3

    authors： Zhao L,Allanson NM,Thomson SP,Maclean JK,Barker JJ,Primrose WU,Tyler PD,Lewendon A

    更新日期：2003-04-01 00:00:00

  • Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide.

    abstract：:Two novel series of 4-thiazolidinone derivatives, namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4-thiazolidinone-3-yl]amides (5a-g) and 2-(2',4'-difluoro-4-hydroxybiphenyl-3-carbonylhydrazono)-3-alkyl/aryl-4-thiazolidinones (6a-e) together with 5-(2',4'-difluoro-4-hy...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.11.005

    authors： Küçükgüzel G,Kocatepe A,De Clercq E,Sahin F,Güllüce M

    更新日期：2006-03-01 00:00:00

  • Repurposing ibuprofen to control Staphylococcus aureus biofilms.

    abstract：:Drug repurposing arises as an interesting alternative to overcome the limited efficacy of current available antibiotics by reducing time, cost and risk associated with drug innovation. In this study, the activity of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), was evaluated on the control of pre-establis...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.01.046

    authors： Oliveira IM,Borges A,Borges F,Simões M

    更新日期：2019-03-15 00:00:00

  • Synthesis and neuromuscular blocking activity of 16beta-piperidinosteroidal derivatives.

    abstract：:The synthesis and pharmacological profiles of some new steroidal mono- and bisquaternary ammonium derivatives have been described. The compounds featured have been conceptually derived structurally from two lead structures: pancuronium bromide 1 and chandonium iodide 2. In vitro and in vivo neuromuscular blocking stud...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(00)01205-8

    authors： Jindal DP,Piplani P,Fajrak H,Prior C,Marshall IG

    更新日期：2001-02-01 00:00:00