当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and preliminary evaluation of peptidomimetic inhibitors of human beta-secretase.

Synthesis and preliminary evaluation of peptidomimetic inhibitors of human beta-secretase.

Abstract：

:Based on the structure of OM99-2 and the X-ray crystal structure of its complex with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their beta-secretase inhibition activities were measured. It was found that isobutyl group was a better R3 substitution as C-terminus in our target compounds, and 4-nitrobenzyl group was the best R2 side chain. With the aid of molecular modeling, the binding modes of compounds 9 and 22 with beta-secretase were compared. The result revealed a stronger bonding mode of 22 than 9. This explored that the optimal length of this series of peptidomimetic inhibitors was P3-P2'. The molecular weights of compounds with this length are around 600.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Niu Y,Wang Y,Zou X,Yang X,Ma C,Lü Y,Zhou B,Yuan Y,Du G,Xu P

doi

10.1016/j.ejmech.2010.01.044

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

2089-94

issue

5

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(10)00089-9

journal_volume

45

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Angiotensin II--AT1 receptor antagonists: design, synthesis and evaluation of substituted carboxamido benzimidazole derivatives.

    abstract：:A series of 5-(alkyl and aryl)carboxamido benzimidazole derivatives had been designed, synthesized and evaluated for in vitro angiotensin II--AT1 receptor antagonism and in vivo antihypertensive activities. The pharmacological activities were inversely related to the size of alkyl and aryl substituents. It can be sugg...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.11.008

    authors： Shah DI,Sharma M,Bansal Y,Bansal G,Singh M

    更新日期：2008-09-01 00:00:00

  • An investigation into the role of surfactants in controlling particle size of polymeric nanocapsules containing penicillin-G in double emulsion.

    abstract：:Preparation, characterization and drug release behavior of loaded polybutyl adipate (PBA) nanocapsules with penicillin-G are described here. The nanocapsules were produced using a double emulsion solvent evaporation technique, using dichloromethane as an organic solvent and Tween and Span as surfactants. In this proce...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.09.045

    authors： Khoee S,Yaghoobian M

    更新日期：2009-06-01 00:00:00

  • Optimization of pharmacokinetic properties by modification of a carbazole-based cannabinoid receptor subtype 2 (CB2) ligand.

    abstract：:Recently, the development of the fluorinated PET tracer [18F]1a for imaging of CB2 receptors in the central nervous system was reported. [18F]1a showed high CB2 affinity and selectivity over the CB1 subtype, but rapid biotransformation in mice. In addition to the amide hydrolysis, oxidative N-dealkylation and carbazol...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.10.049

    authors： Heimann D,Börgel F,de Vries H,Bachmann K,Rose VE,Frehland B,Schepmann D,Heitman LH,Wünsch B

    更新日期：2018-01-01 00:00:00

  • In vitro and in vivo biological evaluation of new 4,5-disubstituted 1,2,3-triazoles as cis-constrained analogs of combretastatin A4.

    abstract：:To find new and better antivascular agents for cancer therapy, a series of combretastatin A4 (CA4) analogs were prepared from 1,3-diaryl-2-nitroprop-1-enes (6-12) obtained in a two-step synthesis from appropriate arylaldehydes and 2-aryl-1-nitroethanes (4 or 5). Treatment of these 1,3-diaryl-2-nitroprop-1-enes 6-12 by...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.04.017

    authors： Mur Blanch N,Chabot GG,Quentin L,Scherman D,Bourg S,Dauzonne D

    更新日期：2012-08-01 00:00:00

  • Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain.

    abstract：:Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.05.032

    authors： Shingate BB,Hazra BG,Salunke DB,Pore VS,Shirazi F,Deshpande MV

    更新日期：2011-09-01 00:00:00

  • Synthesis and immunofluorescence assay of a new biotinylated paclitaxel.

    abstract：:7-(5'-Biotinylamidopropanoyl)paclitaxel was synthesised by chemical methods; its immunofluorescence assay and the cell uptake experiments were performed by use of human leukemia U937 cells. The results indicate that paclitaxel is arresting cell cycle at the G(2)M phase only. ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(02)01337-5

    authors： Sambaiah T,King KY,Tsay SC,Mei NW,Hakimclahi S,Lai YK,Lieu CH,Hwu JR

    更新日期：2002-04-01 00:00:00

  • Synthesis and evaluation of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(2-(4-substitutedpiperazin-1-yl)acetyl)piperazin-1-yl)quinoline-3-carboxylic acid derivatives as anti-tubercular and antibacterial agents.

    abstract：:A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC val...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.10.055

    authors： Suresh N,Nagesh HN,Renuka J,Rajput V,Sharma R,Khan IA,Kondapalli Venkata Gowri CS

    更新日期：2014-01-01 00:00:00

  • Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR.

    abstract：:Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR)...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.09.032

    authors： Zhang Q,Shen Q,Gao L,Tong L,Li J,Chen Y,Lu W

    更新日期：2018-10-05 00:00:00

  • Synthesis of quinoidal molecules: strategies towards bioactive compounds with an emphasis on lapachones.

    abstract：:Naphthoquinoidal compounds are of great interest in medicinal chemistry. In recent years, several synthetic routes have been developed to obtain bioactive molecules derived from lapachones. In this mini-review, we focus on the synthetic aspects and strategies used to design these compounds and on the biological activi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2013.07.057

    authors： de Castro SL,Emery FS,da Silva Júnior EN

    更新日期：2013-11-01 00:00:00

  • Synthesis and pharmacological evaluation of 2(3H)-furanones and 2(3H)-pyrrolones, combining analgesic and anti-inflammatory properties with reduced gastrointestinal toxicity and lipid peroxidation.

    abstract：:A series of 3-arylidene-5-(4-chloro-phenyl)-2(3H)-furanones (2-13) and their nitrogen analogues 1-benzylpyrrolones (14-18) were synthesized. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. Some of the newly synthesized compounds showed good anti-inflamma...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.10.030

    authors： Alam MM,Husain A,Hasan SM,Suruchi,Anwer T

    更新日期：2009-06-01 00:00:00

  • Synthesis of novel cinnamanilides as potential immunosuppressive agents.

    abstract：:A series of new cinnamanilides (6-40) were synthesized and their immunosuppressive activity and cytotoxicity were evaluated. Most of the cinnamanilides showed good immunosuppressive activity. Among the synthesized compounds, (Z)-N-(4-bromophenyl)-2-methoxy-3-(4-methoxyphenyl)acrylamide (37) and (Z)-2-methoxy-3-(4-meth...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.10.027

    authors： Shi L,Wang L,Wang Z,Zhu HL,Song Q

    更新日期：2012-01-01 00:00:00

  • Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterial and anticandida activity.

    abstract：:Thirty-six 6(7)-substituted-3-methyl- or 3-halogenomethyl-2-phenylthio-phenylsulphonyl-chloro-quinoxaline 1,4-dioxides belonging to series 3-6 were synthesised and submitted to a preliminary in vitro evaluation for antimycobacterial, anticandida and antibacterial activities. Antitubercular screening showed a generally...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(02)01346-6

    authors： Carta A,Paglietti G,Rahbar Nikookar ME,Sanna P,Sechi L,Zanetti S

    更新日期：2002-05-01 00:00:00

  • Quantitative structure activity relationship studies of diaryl furanones as selective COX-2 inhibitors.

    abstract：:Selective COX-2 inhibitors have attracted much attention in recent times in the design of non-steroidal anti-inflammatory agents (NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of diaryl furanones that acts as selective COX-2 inhibitor using Molecu...

    journal_title：European journal of medicinal chemistry

    pub_type： 更正并重新发布的文章,杂志文章

    doi：10.1016/j.ejmech.2004.06.005

    authors： Shahapurkar S,Pandya T,Kawathekar N,Chaturvedi SC

    更新日期：2004-10-01 00:00:00

  • Oxazolidinone derivatives: cytoxazone-linezolid hybrids induces apoptosis and senescence in DU145 prostate cancer cells.

    abstract：:In this study, we report the synthesis of novel oxazolidinone derivatives derived from linezolid 3 having p-methoxyphenyl group at C-4 position. In vitro evaluation for their anticancer activity toward cultured A549, DU145, HELA, and MCF7 were carried out. The series of compounds prepared displayed wide range of cytot...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.04.062

    authors： Naresh A,Venkateswara Rao M,Kotapalli SS,Ummanni R,Venkateswara Rao B

    更新日期：2014-06-10 00:00:00

  • Synthesis, molecular docking and biological evaluation of Schiff base transition metal complexes as potential urease inhibitors.

    abstract：:Six transition metal compounds of Schiff base ligands were evaluated for the inhibitory activity on jack bean urease, of which compounds 2-6 were determined by single crystal X-ray analysis. It was found that copper(II) complexes 1 and 4 showed strong inhibitory activity against jack bean urease (IC(50) = 0.52 and 0.4...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.07.007

    authors： Chen W,Li Y,Cui Y,Zhang X,Zhu HL,Zeng Q

    更新日期：2010-10-01 00:00:00

  • A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting Aurora B kinase activity.

    abstract：:Aurora kinases play a key role in the regulation of mitosis and have been regarded as promising targets of cancer therapy. In this paper we describe a thienopyrimidine derivative (S7), a novel potent ATP-competitive hit inhibitor of Aurora B kinase screened through a HTS system, with the IC50 141.12 nM in the biochemi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.04.058

    authors： Li J,Hu H,Lang Q,Zhang H,Huang Q,Wu Y,Yu L

    更新日期：2013-07-01 00:00:00

  • Application of (quantitative) structure-activity relationships to progestagens: from serendipity to structure-based design.

    abstract：:Progestagens are drugs, which are widely used in hormonal contraception and in hormone-replacement therapy. Since the natural hormone, progesterone, lacks oral activity, much effort has been devoted to finding analogues with improved oral activity and, preferably, higher potency and selectivity. A crystal structure of...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/s0223-5234(00)00168-9

    authors： Bursi R,Groen MB

    更新日期：2000-09-01 00:00:00

  • Prenylflavonoids and prenyl/alkyl-phloroacetophenones: synthesis and antitumour biological evaluation.

    abstract：:Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.06.025

    authors： Basabe P,de Román M,Marcos IS,Diez D,Blanco A,Bodero O,Mollinedo F,Sierra BG,Urones JG

    更新日期：2010-09-01 00:00:00

  • A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis.

    abstract：:We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycoba...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.06.014

    authors： Silva RS,Pinto Mdo C,Goulart MO,de Souza Filho JD,Neves I Jr,Lourenço MC,Pinto AV

    更新日期：2009-05-01 00:00:00

  • Design, synthesis and bioactivities of TAR RNA targeting beta-carboline derivatives based on Tat-TAR interaction.

    abstract：:A series of new beta-carboline derivatives 3-14 bearing guanidinium group or amino group-terminated side chain targeting the TAR RNA were designed and synthesized. Molecular modeling studies indicated that the minimal interaction energy was obtained for compound 11, which contained the optimal linker of three methylen...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.01.012

    authors： Yu X,Lin W,Pang R,Yang M

    更新日期：2005-09-01 00:00:00

  • Additivity or cooperativity: which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?

    abstract：:Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data fro...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.11.056

    authors： Nasief NN,Hangauer D

    更新日期：2015-01-27 00:00:00

  • Synthesis of new chalcone derivatives containing a rhodanine-3-acetic acid moiety with potential anti-bacterial activity.

    abstract：:With an intention to synergize the anti-bacterial activity of chalcones and rhodanine-3-acetic acid, several hybrid compounds possessing chalcone and rhodanine-3-acetic acid moieties were synthesized and tested for their anti-bacterial activity. Some compounds presented great anti-microbial activities against Gram-pos...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.09.031

    authors： Chen ZH,Zheng CJ,Sun LP,Piao HR

    更新日期：2010-12-01 00:00:00

  • Optimization of troglitazone derivatives as potent anti-proliferative agents: towards more active and less toxic compounds.

    abstract：:Δ2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPARγ-independent manner. We prepared various compounds in order to increase their potency and decrease their toxicity towards non-malignant primary cultured hepatocytes. Many compounds induced viabilities less than 20% at 10 μM on vari...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.06.015

    authors： Bordessa A,Colin-Cassin C,Grillier-Vuissoz I,Kuntz S,Mazerbourg S,Husson G,Vo M,Flament S,Martin H,Chapleur Y,Boisbrun M

    更新日期：2014-08-18 00:00:00

  • Xanthine oxidase inhibitory activity of natural and hemisynthetic flavonoids from Gardenia oudiepe (Rubiaceae) in vitro and molecular docking studies.

    abstract：:Xanthine oxidase (XO), an enzyme widely distributed among mammalian tissues, is associated with the oxidation of xanthine and hypoxanthine to form uric acid. Reactive oxygen species are also released during this process, leading to oxidative damages and to the pathology called gout. Available treatments mainly based o...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.11.071

    authors： Santi MD,Paulino Zunini M,Vera B,Bouzidi C,Dumontet V,Abin-Carriquiry A,Grougnet R,Ortega MG

    更新日期：2018-01-01 00:00:00

  • Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells.

    abstract：:A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). I...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.04.004

    authors： Wang L,Ai M,Yu J,Jin L,Wang C,Liu Z,Shu X,Tang Z,Liu K,Luo H,Guan W,Sun X,Ma X

    更新日期：2019-06-15 00:00:00

  • Design and synthesis of novel indole-chalcone fibrates as lipid lowering agents.

    abstract：:A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.04.085

    authors： Sashidhara KV,Dodda RP,Sonkar R,Palnati GR,Bhatia G

    更新日期：2014-06-23 00:00:00

  • Synthesis, biological evaluation, and molecular docking study of 3-(3'-heteroatom substituted-2'-hydroxy-1'-propyloxy) xanthone analogues as novel topoisomerase IIα catalytic inhibitor.

    abstract：:Epoxide ring-opened xanthone derivatives were synthesized and tested for their topoisomerase inhibitory activity and cytotoxicity. Most of the compounds showed topo IIα specific inhibitory activity. To clarify the mechanism of action of these compounds, the most potent compound (compound 14) of the synthesized analogu...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.01.011

    authors： Jun KY,Lee EY,Jung MJ,Lee OH,Lee ES,Park Choo HY,Na Y,Kwon Y

    更新日期：2011-06-01 00:00:00

  • 2-(2-Hydrazinyl)thiazole derivatives: design, synthesis and in vitro antimycobacterial studies.

    abstract：:In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.08.054

    authors： Makam P,Kankanala R,Prakash A,Kannan T

    更新日期：2013-11-01 00:00:00

  • Synthesis and biological evaluation of new pyrazol-4-ylpyrimidine derivatives as potential ROS1 kinase inhibitors.

    abstract：:With the aim of discovering potent and selective kinase inhibitors targeting ROS1 kinase, we designed, synthesized and screened a series of new pyrazol-4-ylpyrimidine derivatives based on our previously discovered lead compound KIST301072. Compounds 6a-e and 7a-e showed good to excellent activities against ROS1 kinase...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.11.023

    authors： Abdelazem AZ,Al-Sanea MM,Park BS,Park HM,Yoo KH,Sim T,Park JB,Lee SH,Lee SH

    更新日期：2015-01-27 00:00:00

  • Tetrazole hybrids and their antifungal activities.

    abstract：:Fungi, which can cause serious infections, results in more than 1.35 million deaths annually throughout the world. Azole antifungal drugs which could inhibit the enzyme lanosterol 14α-demethylase, occupy an important position in the treatment of fungal infections. Tetrazoles, practically non-metabolized bioisosteric a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2019.03.023

    authors： Wang SQ,Wang YF,Xu Z

    更新日期：2019-05-15 00:00:00