当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein.

Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein.

Abstract：

:Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1(I1061T) mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1(I1061T) mutant.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ohgane K,Karaki F,Noguchi-Yachide T,Dodo K,Hashimoto Y

doi

10.1016/j.bmcl.2014.05.064

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

3480-5

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00564-2

journal_volume

24

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents.

    abstract：:A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines was prepared and tested for its in vitro cytotoxic activity against a panel of 12 human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity and were further tested for their in vivo efficacy in the HT-29 human colon ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.10.020

    authors： Sharma VM,Adi Seshu KV,Chandra Sekhar V,Madan S,Vishnu B,Babu PA,Vamsee Krishna C,Sreenu J,Ravi Krishna V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Kumar TS

    更新日期：2004-01-05 00:00:00

  • Antitumour benzothiazoles. Part 10: the synthesis and antitumour activity of benzothiazole substituted quinol derivatives.

    abstract：:The synthesis of a series of new antitumour agents, the benzothiazole substituted quinol ethers and esters, is reported via the hypervalent iodine mediated oxidation of hydroxylated 2-phenylbenzothiazoles. The products were found to be active in vitro against human colon and breast cancer cell lines with IC50 values i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00027-5

    authors： Wells G,Bradshaw TD,Diana P,Seaton A,Shi DF,Westwell AD,Stevens MF

    更新日期：2000-03-06 00:00:00

  • Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors.

    abstract：:A series of conformationally constrained 3-(N-alkylamino)propylphosphonic acids were systematically synthesized and their activities as S1P receptor agonists were evaluated. Several pyrrolidine and cyclohexane analogs had S1P receptor profiles comparable to the acyclic lead compound, 3-(N-tetradecylamino)propylphospho...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.049

    authors： Yan L,Hale JJ,Lynch CL,Budhu R,Gentry A,Mills SG,Hajdu R,Keohane CA,Rosenbach MJ,Milligan JA,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala SM

    更新日期：2004-10-04 00:00:00

  • N-4-Substituted-benzyl-N'-tert-butylbenzyl thioureas as vanilloid receptor ligands: investigation on the role of methanesulfonamido group in antagonistic activity.

    abstract：:A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that not only the two oxygens and amide hydrogen of sulfonamido group, but also the optimal...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.11.019

    authors： Park HG,Choi JY,Choi SH,Park MK,Lee J,Suh YG,Cho H,Oh U,Lee J,Kang SU,Lee J,Kim HD,Park YH,Su Jeong Y,Kyu Choi J,Jew SS

    更新日期：2004-02-09 00:00:00

  • Spirocyclic NK(1) antagonists I: [4.5] and [5.5]-spiroketals.

    abstract：:A series of novel spiroketal-based NK(1) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00506-1

    authors： Seward EM,Carlson E,Harrison T,Haworth KR,Herbert R,Kelleher FJ,Kurtz MM,Moseley J,Owen SN,Owens AP,Sadowski SJ,Swain CJ,Williams BJ

    更新日期：2002-09-16 00:00:00

  • Cluster analysis and two-dimensional quantitative structure-activity relationship (2D-QSAR) of Pseudomonas aeruginosa deacetylase LpxC inhibitors.

    abstract：:Compounds from a wide variety of structural classes inhibit Pseudomonas aeruginosa deacetylase LpxC. However, a single unified understanding of the relationship between the structures and activities of these compounds still eludes the researchers. We report herein, the development of cluster analysis-based 2D-QSAR mod...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.07.041

    authors： Kadam RU,Roy N

    更新日期：2006-10-01 00:00:00

  • Synthesis and SAR of azalide 3,6-ketal aromatic derivatives as potent Gram-positive and Gram-negative antibacterial agents.

    abstract：:3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00434-1

    authors： Cheng H,Dirlam JP,Ziegler CB,Lundy KM,Hayashi SF,Kamicker BJ,Dutra JK,Daniel KL,Santoro SL,George DM,Bertsche CD,Sakya SM,Suarez-Contreras M

    更新日期：2002-09-02 00:00:00

  • Therapeutic potential of coumarin bearing metal complexes: Where are we headed?

    abstract：:The successfully application of some metallodrugs such as salvarsan, silver sulfadiazine and cisplatin in modern medicine launched the biological investigation of organometallic and metal-organic complexes. The availability and tunability of various ligands including N-heterocycles, phosphines, N-heterocyclic carbenes...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2019.126805

    authors： Balcıoğlu S,Olgun Karataş M,Ateş B,Alıcı B,Özdemir İ

    更新日期：2020-01-15 00:00:00

  • 2-Amino-[1,2,4]triazolo[1,5-a]pyridines as JAK2 inhibitors.

    abstract：:The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.008

    authors： Siu M,Pastor R,Liu W,Barrett K,Berry M,Blair WS,Chang C,Chen JZ,Eigenbrot C,Ghilardi N,Gibbons P,He H,Hurley CA,Kenny JR,Cyrus Khojasteh S,Le H,Lee L,Lyssikatos JP,Magnuson S,Pulk R,Tsui V,Ultsch M,Xiao Y,Zh

    更新日期：2013-09-01 00:00:00

  • N-DEVD-N'-morpholinecarbonyl-rhodamine 110: novel caspase-3 fluorogenic substrates for cell-based apoptosis assay.

    abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.081

    authors： Wang ZQ,Liao J,Diwu Z

    更新日期：2005-05-02 00:00:00

  • The first steps. The attack on the carbonyl carbon of pyridoxal cofactor in pyridoxal-dependent enzymes.

    abstract：:A study of the reaction between gaseous aldehydes and amines has implicated proton transfer from wall-associated water. Carbinolamine formation and subsequent dehydration to imine with assistance by wall associated hydroxyl bearing species has not previously been specifically suggested to obtain in the multitude of en...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.11.051

    authors： Sonnet PE,Mascavage LM,Dalton DR

    更新日期：2008-01-15 00:00:00

  • Synthesis and evaluation of 4-triazolylflavans as new aromatase inhibitors.

    abstract：:Aromatase is a target of pharmacological interest for the treatment of estrogen-dependent cancers. Azole derivatives such as letrozole or anastrozole have been developed for aromatase inhibition and are used for the treatment of breast tumors. In this paper, four 4-triazolylflavans were synthesized and were found to e...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.090

    authors： Yahiaoui S,Pouget C,Fagnere C,Champavier Y,Habrioux G,Chulia AJ

    更新日期：2004-10-18 00:00:00

  • An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury.

    abstract：:Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00733-9

    authors： Velentza AV,Wainwright MS,Zasadzki M,Mirzoeva S,Schumacher AM,Haiech J,Focia PJ,Egli M,Watterson DM

    更新日期：2003-10-20 00:00:00

  • A bivalent ligand (KMN-21) antagonist for mu/kappa heterodimeric opioid receptors.

    abstract：:In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodime...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.045

    authors： Zhang S,Yekkirala A,Tang Y,Portoghese PS

    更新日期：2009-12-15 00:00:00

  • Synthesis of 2'-O,4'-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase.

    abstract：:The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'-C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.04.050

    authors： Chapron C,Glen R,La Colla M,Mayes BA,McCarville JF,Moore S,Moussa A,Sarkar R,Seifer M,Serra I,Stewart A

    更新日期：2014-06-15 00:00:00

  • Study on structure-activity relationship of vitamin K derivatives: Conversion of the naphthoquinone part into another aromatic ring and evaluation of their neuronal differentiation-inducing activity.

    abstract：:We synthesized novel vitamin K derivatives by converting the naphthoquinone group to benzene derivatives and benzoquinone. We evaluated their neuronal differentiation activities to investigate the effect of the quinone moiety on this process. We observed that the 1,4-quinone as well as the side chain part play importa...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127059

    authors： Yoshimura H,Hirota Y,Soda S,Okazeri M,Takagi Y,Takeuchi A,Tode C,Kamao M,Osakabe N,Suhara Y

    更新日期：2020-04-15 00:00:00

  • Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents.

    abstract：:Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.07.010

    authors： Lv PC,Li DD,Li QS,Lu X,Xiao ZP,Zhu HL

    更新日期：2011-09-15 00:00:00

  • Optimization of 3-phenylpyrazolo[1,5-a]pyrimidines as potent corticotropin-releasing factor-1 antagonists with adequate lipophilicity and water solubility.

    abstract：:In our efforts to identify potent CRF(1) antagonists with proper physicochemical properties, a series of 3-phenylpyrazolo[1,5-a]pyrimidines bearing polar groups, such as amino, hydroxyl, methoxy, sulfoxide, were designed and synthesized. Several positions of the core structure were identified, where a polar group was ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.05.019

    authors： Chen C,Wilcoxen KM,Huang CQ,McCarthy JR,Chen T,Grigoriadis DE

    更新日期：2004-07-16 00:00:00

  • Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives.

    abstract：:We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.05.064

    authors： Matsumoto K,Choshi T,Hourai M,Zamami Y,Sasaki K,Abe T,Ishikura M,Hatae N,Iwamura T,Tohyama S,Nobuhiro J,Hibino S

    更新日期：2012-07-15 00:00:00

  • NEW BASE-ALTERED ADENOSINE ANALOGUES: SYNTHESIS AND AFFINITY AT ADENOSINE A1 and A2A RECEPTORS.

    abstract：:N6-Substituted adenosine analogues containing cyclic hydrazines or chiral hydroxy (ar)alkyl groups, designed to interact with the S2 and S3 receptor subregions, have been synthesized and their binding to the adenosine A1 and A2A receptors have been investigated. Examples of both types of compounds were found to exhibi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/S0960-894X(97)10177-9

    authors： Ha SB,Melman N,Jacobson KA,Nair V

    更新日期：1997-12-16 00:00:00

  • Discovery of fused 5,6-bicyclic heterocycles as γ-secretase modulators.

    abstract：:We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.12.012

    authors： Qin J,Dhondi P,Huang X,Mandal M,Zhao Z,Pissarnitski D,Zhou W,Aslanian R,Zhu Z,Greenlee W,Clader J,Zhang L,Cohen-Williams M,Jones N,Hyde L,Palani A

    更新日期：2011-01-15 00:00:00

  • Identification of novel estrogen receptor (ER) agonists that have additional and complementary anti-cancer activities via ER-independent mechanism.

    abstract：:In this study, a series of bis(4-hydroxy)benzophenone oxime ether derivatives such as 12c, 12e and 12h were identified as novel estrogen receptor (ER) agonists that have additional and complementary anti-proliferative activities via ER-independent mechanism in cancer cells. These compounds are expected to overcome the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.01.089

    authors： Kim T,Kim HI,An JY,Lee J,Lee NR,Heo J,Kim JE,Yu J,Lee YS,Inn KS,Kim NJ

    更新日期：2016-04-01 00:00:00

  • Synthesis and structure-activity relationships of oxime neurokinin antagonists: discovery of potent arylamides.

    abstract：:The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00709-0

    authors： Shih NY,Albanese M,Anthes JC,Carruthers NI,Grice CA,Lin L,Mangiaracina P,Reichard GA,Schwerdt J,Seidl V,Wong SC,Piwinski JJ

    更新日期：2002-01-21 00:00:00

  • Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of isozymes I and II.

    abstract：:The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citalopram have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: hi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00507-9

    authors： Casini A,Caccia S,Scozzafava A,Supuran CT

    更新日期：2003-08-18 00:00:00

  • Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes.

    abstract：:Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.095

    authors： da S Souza LG,Almeida MCS,Lemos TLG,Ribeiro PRV,de Brito ES,Silva VLM,Silva AMS,Braz-Filho R,Costa JGM,Rodrigues FFG,Barreto FS,de Moraes MO

    更新日期：2016-01-15 00:00:00

  • Synthesis and antiprotozoal activity of nitazoxanide-N-methylbenzimidazole hybrids.

    abstract：:A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.10.011

    authors： Soria-Arteche O,Hernández-Campos A,Yépez-Mulia L,Trejo-Soto PJ,Hernández-Luis F,Gres-Molina J,Maldonado LA,Castillo R

    更新日期：2013-12-15 00:00:00

  • N-Heteroaryl glycinamides and glycinamines as potent NPY5 antagonists.

    abstract：:Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimizati...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.06.078

    authors： Wu L,Lu K,Desai M,Packiarajan M,Joshi A,Marzabadi MR,Jubian V,Andersen K,Chandrasena G,Boyle NJ,Walker MW

    更新日期：2011-09-15 00:00:00

  • Novel halogenated nitrobenzylthioinosine analogs as es nucleoside transporter inhibitors.

    abstract：:Nucleoside transporter inhibitors have potential therapeutic applications as anticancer, antiviral, cardioprotective, and neuroprotective agents. We have synthesized and flow cytometrically evaluated the binding affinity of a series of novel halogenated nitrobenzylthioinosine analogs at the human es nucleoside transpo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.02.016

    authors： Gupte A,Buolamwini JK

    更新日期：2004-05-03 00:00:00

  • Non-peptidic phenyl-based thrombin inhibitors: exploring structural requirements of the S1 specificity pocket with amidines.

    abstract：:We expand the structural requirements and structure-activity relationship of a novel class of non-peptidic aryl-based thrombin inhibitors through exploration of the S1 specificity pocket of thrombin using flexible and constrained amidines. The most active compound of this class is 11 with Ki = 69 nM, which is ca. 15-f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00616-2

    authors： Lu T,Tomczuk B,Bone R,Murphy L,Salemme FR,Soll RM

    更新日期：2000-01-03 00:00:00

  • Inhibitory effect of Rhus verniciflua Stokes extract on human aromatase activity; butin is its major bioactive component.

    abstract：:Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione wa...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.02.039

    authors： Park MH,Kim IS,Kim SA,Na CS,Hong CY,Dong MS,Yoo HH

    更新日期：2014-04-01 00:00:00