当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis, and evaluation of Leu*Ala hydroxyethylene-based non-peptide beta-secretase (BACE) inhibitors.

Design, synthesis, and evaluation of Leu*Ala hydroxyethylene-based non-peptide beta-secretase (BACE) inhibitors.

Abstract：

:With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600).

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Xiao K,Li X,Li J,Ma L,Hu B,Yu H,Fu Y,Wang R,Ma Z,Qiu B,Li J,Hu D,Wang X,Shen J

doi

10.1016/j.bmc.2006.02.024

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

4535-51

issue

13

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(06)00175-1

journal_volume

14

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Benzodiazepine receptor ligands. 8: synthesis and pharmacological evaluation of new pyrazolo[5,1-c] [1,2,4]benzotriazine 5-oxide 3- and 8-disubstituted: high affinity ligands endowed with inverse-agonist pharmacological efficacy.

    abstract：:The synthesis and the binding study of new 3-arylesters and 3-heteroarylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-substituted are reported. The nature of these substituents (in terms of lipophilic and electronic features) seems to influence the binding affinity. High-affinity ligands were studied in mice in vivo f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.08.058

    authors： Guerrini G,Costanzo A,Ciciani G,Bruni F,Selleri S,Costagli C,Besnard F,Costa B,Martini C,De Siena G,Malmberg-Aiello P

    更新日期：2006-02-01 00:00:00

  • Investigating the role of the geminal dimethyl groups of coenzyme A: synthesis and studies of a didemethyl analogue.

    abstract：:An analogue 2 of coenzyme A (CoA) has been prepared in which the geminal methyl groups are replaced with hydrogens. An NMR titration study was conducted and shifts in frequency of protons in the pantetheine portion of the molecule upon titration of the adenine base were observed as has been previously reported with Co...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00189-9

    authors： Vogel KW,Stark LM,Mishra PK,Yang W,Drueckhammer DG

    更新日期：2000-10-01 00:00:00

  • Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins.

    abstract：:Glucoconjugated tri and tetra(meta-hydroxyphenyl)chlorins have been synthesized in order to explore how glucoconjugation of the macrocycle affects the photoactivity of the molecule. Internalization processes, photosensitizing efficacy of TPC(m-O-GluOH)(3) and TPC(m-O-GluOH)(4), in HT29 human adenocarcinoma cells have ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00050-6

    authors： Laville I,Figueiredo T,Loock B,Pigaglio S,Maillard P,Grierson DS,Carrez D,Croisy A,Blais J

    更新日期：2003-04-17 00:00:00

  • Active site mapping of trypsin, thrombin and matriptase-2 by sulfamoyl benzamidines.

    abstract：:The benzamidine moiety, a well-known arginine mimetic, has been introduced in a variety of ligands, including peptidomimetic inhibitors of trypsin-like serine proteases. According to their primary substrate specificity, the benzamidine residue interacts with the negatively charged aspartate at the bottom of the S1 poc...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.08.042

    authors： Dosa S,Stirnberg M,Lülsdorff V,Häußler D,Maurer E,Gütschow M

    更新日期：2012-11-01 00:00:00

  • Synthesis and in vitro characterization of platinum(II) anticancer coordinates using FTIR spectroscopy and NCI COMPARE: A fast method for new compound discovery.

    abstract：:Platinum-based drugs have been used for several decades to treat various cancers successfully. Cisplatin is the original compound in this class; it cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types but exhibits toxic side effects; in additi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.04.017

    authors： Berger G,Leclercqz H,Derenne A,Gelbcke M,Goormaghtigh E,Nève J,Mathieu V,Dufrasne F

    更新日期：2014-07-01 00:00:00

  • High-throughput evaluation of relative cell permeability between peptoids and peptides.

    abstract：:Peptides are limited in their use as drugs due to low cell permeability and vulnerability to proteases. In contrast, peptoids are immune to enzymatic degradation and some peptoids have been shown to be relatively cell permeable. In order to facilitate future design of peptoid libraries for screening experiments, it wo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.04.074

    authors： Tan NC,Yu P,Kwon YU,Kodadek T

    更新日期：2008-06-01 00:00:00

  • Chemical synthesis, cytotoxicity, selectivity and bioavailability of 5α-androstane-3α,17β-diol derivatives.

    abstract：:Aminosteroid derivatives represent a new family of compounds with promising antiproliferative activity over different cancer cell lines. Among all the aminosteroid derivatives synthesised in our laboratory, we have identified E-37P as one of the more potent when tested in vitro. Unfortunately, the pharmacokinetic prop...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.09.026

    authors： Ayan D,Maltais R,Hospital A,Poirier D

    更新日期：2014-11-01 00:00:00

  • Synthesis and structure-activity relationships of benzyloxyphenyl derivatives as a novel class of NCX inhibitors: effects on heart failure.

    abstract：:In the context of heart failure and myocardial ischemia reperfusion, the activity of the sodium-calcium exchanger can lead to calcium overload, which in turn can lead to contractile dysfunction and arrhythmia. Therefore, NCX is an attractive target for treatment of heart failure and myocardial ischemia reperfusion. We...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.10.048

    authors： Kuramochi T,Kakefuda A,Yamada H,Ogiyama T,Taguchi T,Sakamoto S

    更新日期：2005-02-01 00:00:00

  • Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors.

    abstract：:In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that mos...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.02.003

    authors： Zhai X,Bao G,Wang L,Cheng M,Zhao M,Zhao S,Zhou H,Gong P

    更新日期：2016-03-15 00:00:00

  • Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis.

    abstract：:A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfact...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.01.047

    authors： Zhong Y,Xue M,Zhao X,Yuan J,Liu X,Huang J,Zhao Z,Li H,Xu Y

    更新日期：2013-04-01 00:00:00

  • Synthesis and immunochemical characterization of protein conjugates of carbohydrate and carbohydrate-mimetic peptides as experimental vaccines.

    abstract：:The peptides DRPVPY and MDWNMHAA, which were identified as mimics of the cell-surface polysaccharides of Streptococcus Group A and Shigella flexneri Y, respectively, were used in this study to develop experimental vaccines directed against these two bacteria. Both oligopeptides were synthesized employing the Fmoc soli...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.03.075

    authors： Hossany RB,Johnson MA,Eniade AA,Pinto BM

    更新日期：2004-07-01 00:00:00

  • Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor.

    abstract：:Janus kinases (JAKs) are considered promising targets for the treatment of autoimmune diseases including rheumatoid arthritis (RA) due to their important role in multiple cytokine receptor signaling pathways. Recently, several JAK inhibitors have been developed for the treatment of RA. Here, we describe the identifica...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.08.005

    authors： Hamaguchi H,Amano Y,Moritomo A,Shirakami S,Nakajima Y,Nakai K,Nomura N,Ito M,Higashi Y,Inoue T

    更新日期：2018-10-01 00:00:00

  • 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion.

    abstract：:A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyraz...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.09.036

    authors： Sayer JR,Walldén K,Pesnot T,Campbell F,Gane PJ,Simone M,Koss H,Buelens F,Boyle TP,Selwood DL,Waksman G,Tabor AB

    更新日期：2014-11-15 00:00:00

  • Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatory activity.

    abstract：:4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues have been found to be compounds of interest for their anti-inflammatory, analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.04.058

    authors： Alam MS,Choi JH,Lee DU

    更新日期：2012-07-01 00:00:00

  • Synthesis and antidepressant-like action of stereoisomers of imidobenzenesulfonylaziridines in mice evaluated in the forced swimming test.

    abstract：:The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the imm...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.03.036

    authors： Duarte FS,Andrade Eda S,Vieira RA,Uieara M,Nunes RJ,de Lima TC

    更新日期：2006-08-01 00:00:00

  • SAR studies of acidic dual γ-secretase/PPARγ modulators.

    abstract：:A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.08.003

    authors： Hieke M,Ness J,Steri R,Greiner C,Werz O,Schubert-Zsilavecz M,Weggen S,Zettl H

    更新日期：2011-09-15 00:00:00

  • Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors.

    abstract：:The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selectiv...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.070

    authors： Chimenti F,Secci D,Bolasco A,Chimenti P,Granese A,Carradori S,Maccioni E,Cardia MC,Yáñez M,Orallo F,Alcaro S,Ortuso F,Cirilli R,Ferretti R,Distinto S,Kirchmair J,Langer T

    更新日期：2010-07-15 00:00:00

  • Optimizing phenylethylphosphonamidates for the inhibition of prostate-specific membrane antigen.

    abstract：:A series of eight N-2-phenylethylphosphonyl derivatives of glutamic acid was prepared to determine if the inhibitory potency of a phenylethylphosphonyl derivative of glutamic acid against prostate-specific membrane antigen (PSMA) could be improved through rational substitutions on the phenyl ring. The design of these ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.07.056

    authors： Wone DW,Rowley JA,Garofalo AW,Berkman CE

    更新日期：2006-01-01 00:00:00

  • Prospects of PASylation® for the design of protein and peptide therapeutics with extended half-life and enhanced action.

    abstract：:Pharmacokinetic (PK) extension is no longer just a means to create improved second generation biologics (so-called biobetters), but constitutes an accepted strategy in biopharmaceutical drug development today. Although PEGylation has become a widely applied methodology to furnish therapeutic proteins and peptides with...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.09.016

    authors： Gebauer M,Skerra A

    更新日期：2018-06-01 00:00:00

  • New triterpenoid saponins with strong alpha-glucosidase inhibitory activity from the roots of Gypsophila oldhamiana.

    abstract：:Seven new triterpenoid saponins (1-7), have been isolated and elucidated from the roots of Gypsophila oldhamiana together with five known triterpenoid saponins (8-12). These saponins which could be classified into three series: 3-O-monoglucosides (1, 8, 9), 28-O-monoglucosides (2-4, 12) and 3, 28-O-bidesmosides (5-7, ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.12.053

    authors： Luo JG,Ma L,Kong LY

    更新日期：2008-03-15 00:00:00

  • Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase.

    abstract：:Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.10.049

    authors： Fu J,Yang Y,Zhang XW,Mao WJ,Zhang ZM,Zhu HL

    更新日期：2010-12-15 00:00:00

  • Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors.

    abstract：:Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115601

    authors： Li Q,Li J,Cai Y,Zou Y,Chen B,Zou F,Mo J,Han T,Guo W,Huang W,Qiu Q,Qian H

    更新日期：2020-08-01 00:00:00

  • A study on the conversion of indanones into carbostyrils.

    abstract：:We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrang...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00116-0

    authors： Torisawa Y,Nishi T,Minamikawa Ji

    更新日期：2003-05-15 00:00:00

  • Synthesis and evaluation of xanomeline analogs--probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor.

    abstract：:A series of xanomeline analogs were synthesized and evaluated for binding at the M(1) muscarinic acetylcholine receptor (M(1) receptor). Specifically, compounds that substitute the O-hexyl chain of xanomeline with polar, ionizable, or conformationally restricted moieties were assessed for their ability to bind to the ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.10.058

    authors： Kane BE,Grant MK,El-Fakahany EE,Ferguson DM

    更新日期：2008-02-01 00:00:00

  • Synergistic reduction of HIV-1 infectivity by 5-azacytidine and inhibitors of ribonucleotide reductase.

    abstract：:Although many compounds have been approved for the treatment of human immunodeficiency type-1 (HIV-1) infection, additional anti-HIV-1 drugs (particularly those belonging to new drug classes) are still needed due to issues such as long-term drug-associated toxicities, transmission of drug-resistant variants, and devel...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.03.052

    authors： Rawson JM,Roth ME,Xie J,Daly MB,Clouser CL,Landman SR,Reilly CS,Bonnac L,Kim B,Patterson SE,Mansky LM

    更新日期：2016-06-01 00:00:00

  • Cell-based biological evaluations of 5-(3-bromo-4-phenethoxybenzylidene)thiazolidine-2,4-dione as promising wound healing agent.

    abstract：:Recent studies have focused on prostaglandin E₂ (PGE₂) because PGE₂ regulates vertebrate hematopoietic stem cell induction and engraftment. PGE₂ acts through EP2 and EP4 receptors to mediate regeneration and hematopoietic stem cell (HSC) development via the Wnt signaling pathway. Previously we reported that inhibitors...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.010

    authors： Piao YL,Ram Song A,Cho H

    更新日期：2015-05-01 00:00:00

  • Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs).

    abstract：:We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.02.055

    authors： Takasugi T,Hanaoka K,Sasaki A,Ikeno T,Komatsu T,Ueno T,Yamada K,Urano Y

    更新日期：2019-05-15 00:00:00

  • Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors.

    abstract：:We have synthesized three categories of α,β-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including α,β-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC₅₀ human MAO-B 16 nM, >6000-fold selective vs MAO-A) ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.08.012

    authors： Choi JW,Jang BK,Cho NC,Park JH,Yeon SK,Ju EJ,Lee YS,Han G,Pae AN,Kim DJ,Park KD

    更新日期：2015-10-01 00:00:00

  • Photodynamic inactivation of Candida albicans using bridged polysilsesquioxane films doped with porphyrin.

    abstract：:Novel photoactive bridged polysilsesquioxane films were prepared by doped with a porphyrin derivative. The films were formed by acid-catalyzed polycondensation reaction of a precursor of a bridged silsesquioxane, based on the reaction product of (glycidoxypropyl)trimethoxysilane with n-dodecylamine in the presence of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.012

    authors： Alvarez MG,Gómez ML,Mora SJ,Milanesio ME,Durantini EN

    更新日期：2012-07-01 00:00:00

  • No carrier added synthesis of O-(2'-[18F]fluoroethyl)-L-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine Schiff base.

    abstract：:O-(2'-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of (18)F (110min) allowing remote-site application. Here we present a novel ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.040

    authors： Krasikova RN,Kuznetsova OF,Fedorova OS,Maleev VI,Saveleva TF,Belokon YN

    更新日期：2008-05-01 00:00:00