当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL.

Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL.

Abstract：

:The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. The original hit 1 was extensively modified through a structure-based drug design strategy, especially by varying the C7 acetamide appendage of the scaffold to exploit extended interactions with P-loop residues. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of ABL are discussed in detail.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Choe H,Kim J,Hong S

doi

10.1016/j.bmcl.2013.05.095

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

4324-7

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00701-4

journal_volume

23

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Alkyl lysophosphatidic acid and fluoromethylene phosphonate analogs as metabolically-stabilized agonists for LPA receptors.

    abstract：:We describe an efficient method for the synthesis of alkyl lysophosphatidic acid (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor agonist activity using a cell migration assay for LPA(1) activation in cancer cells ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.08.019

    authors： Xu Y,Tanaka M,Arai H,Aoki J,Prestwich GD

    更新日期：2004-11-01 00:00:00

  • Design, synthesis and binding affinity of acetylcholine carbamoyl analogues.

    abstract：:A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety or at the cationic head or at both, were tested for binding affinity at muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic affinity was found, submicromolar Ki values, similar to that of carbachol, were measured at α...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.023

    authors： Bolchi C,Valoti E,Binda M,Fasoli F,Ferrara R,Fumagalli L,Gotti C,Matucci R,Vistoli G,Pallavicini M

    更新日期：2013-12-01 00:00:00

  • The discovery of rofecoxib, [MK 966, Vioxx, 4-(4'-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2-inhibitor.

    abstract：:The development of a COX-2 inhibitor rofecoxib (MK 966, Vioxx) is described. It is essentially equipotent to indomethacin both in vitro and in vivo but without the ulcerogenic side effect due to COX-1 inhibition. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00288-7

    authors： Prasit P,Wang Z,Brideau C,Chan CC,Charleson S,Cromlish W,Ethier D,Evans JF,Ford-Hutchinson AW,Gauthier JY,Gordon R,Guay J,Gresser M,Kargman S,Kennedy B,Leblanc Y,Léger S,Mancini J,O'Neill GP,Ouellet M,Percival MD

    更新日期：1999-07-05 00:00:00

  • Synthesis and methemoglobin toxicity of the amides of 6/7 mono or disubstituted quinolone.

    abstract：:A series of 6/7-mono and disubstituted quinolone-3-carboxamide derivatives (1-12) were synthesized and their in vitro methemoglobin producing capacity have been delineated. The compounds 5, 6, 9 and 10 showed minimum methemoglobin toxicity. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00688-x

    authors： Srivastava S,Srivastava SK,Shukla A,Chauhan PM,Puri SK,Bhaduri AP,Pandey VC

    更新日期：1999-01-04 00:00:00

  • Kinetic delay of cyclization/elimination-coupled enzyme assays: analysis and solution.

    abstract：:A kinetic analysis of an enzyme assay employing a synthetic substrate that produces a detectable signal through a spontaneous organic cyclization/elimination reaction following the enzymatic reaction was conducted. The results from the calculation were used to predict the lag period and provide accurate measurements o...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.09.104

    authors： Xue F,Seto CT

    更新日期：2011-02-01 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

  • Cyclobranol: a substrate for C25-methyl sterol side chains and potent mechanism-based inactivator of plant sterol methyltransferase.

    abstract：:Cyclobranol 8A, an analog of the cycloartenol substrate 1A for the plant sterol C24-methyltransferase (SMT), was shown to be an acceptor of the soybean SMT1 as well as an inhibitor of enzyme action. The K(m) and k(cat) for 8A was 37 microM and 0.006 min(-1), respectively. The enzyme-generated product was identified by...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.06.044

    authors： Wang J,Nes WD

    更新日期：2008-07-15 00:00:00

  • Design, semisynthesis and potent cytotoxic activity of novel 10-fluorocamptothecin derivatives.

    abstract：:Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity ag...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.09.012

    authors： Yang CJ,Song ZL,Goto M,Hsu PL,Zhang XS,Yang QR,Liu YQ,Wang MJ,Morris-Natschke SL,Shang XF,Lee KH

    更新日期：2017-10-15 00:00:00

  • 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives as non-peptidic selective delta-opioid agonists with potential anxiolytic/antidepressant properties. Part 2.

    abstract：:Novel 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives have been prepared and their synthesis described herein. In vitro affinities for delta-, micro-, and kappa-opioid receptors are reported. Evaluation of some representative compounds from this series in the mouse neonatal ultrasonic vocalization test and the mo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.05.012

    authors： Trabanco AA,Aerts N,Alvarez RM,Andrés JI,Boeckx I,Fernández J,Gómez A,Janssens FE,Leenaerts JE,De Lucas AI,Matesanz E,Steckler T,Pullan S

    更新日期：2007-07-15 00:00:00

  • Oxidative stimuli-responsive nanoprodrug of camptothecin kills glioblastoma cells.

    abstract：:The purpose of this study was to prepare and characterize nanometer-sized prodrug (nanoprodrug) of camptothecin. The camptothecin prodrug was synthesized using tetraethylene glycol spacer linked via carbonate bond to camptothecin and via ester bond to alpha-lipoic acid. The nanoprodrug was prepared through the spontan...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.144

    authors： Lee BS,Nalla AK,Stock IR,Shear TC,Black KL,Yu JS

    更新日期：2010-09-01 00:00:00

  • Controllable selective synthesis of a polymerizable prodrug of cytarabine by enzymatic and chemical methods.

    abstract：:Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5'-O-acyl cytarabine derivatives in high yields, while the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.06.011

    authors： Wang N,Chen ZC,Lu DS,Lin XF

    更新日期：2005-09-15 00:00:00

  • 6-arylamino-5,8-quinolinediones and 7-arylamino-5,8-isoquinolinediones as inhibitors of endothelium-dependent vasorelaxation.

    abstract：:6-Arylamino-5,8-quinolinediones 3 and 7-arylamino-5,8-isoquinolinediones 4 were synthesized as inhibitors of endothelium-dependent vasorelaxation. The quinones inhibited the vasorelaxation of rat aorta with the endothelium. Among them, the quinones 3a, 3b, 3f, 4b, 4d and 4g strongly inhibited the vasorelaxation. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00411-4

    authors： Ryu CK,Jung SH,Lee JA,Kim HJ,Lee SH,Chung JH

    更新日期：1999-09-06 00:00:00

  • A simple method for predicting serum protein binding of compounds from IC(50) shift analysis for in vitro assays.

    abstract：:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.01.103

    authors： Rusnak DW,Lai Z,Lansing TJ,Rhodes N,Gilmer TM,Copeland RA

    更新日期：2004-05-03 00:00:00

  • Synthesis of enamino-2-oxindoles via conjugate addition between α-azido ketones and 3-alkenyl oxindoles: Cytotoxicity evaluation and apoptosis inducing studies.

    abstract：:A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.07.038

    authors： Kumar NP,Vanjari Y,Thatikonda S,Pooladanda V,Sharma P,Sridhar B,Godugu C,Kamal A,Shankaraiah N

    更新日期：2018-12-01 00:00:00

  • Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors.

    abstract：:Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner-Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the P(2)(') position of keto-ACE resulted in a significant increase in C-domain-se...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.06.003

    authors： Nchinda AT,Chibale K,Redelinghuys P,Sturrock ED

    更新日期：2006-09-01 00:00:00

  • Discovery of highly potent and selective benzyloxybenzyl-based peroxisome proliferator-activator receptor (PPAR) delta agonists.

    abstract：:A series of 1,4-benzyloxybenzylsulfanylaryl carboxylic acids were prepared and their activities for PPAR receptor subtypes (alpha, delta, and gamma) with potential indications for the treatment of dyslipidemia were investigated. Analog 13a displayed the greatest binding affinity (IC(50)=10nM) and selectivity (120-fold...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.04.046

    authors： Bratton LD,Filzen GF,Geyer A,Hoffman JK,Lu G,Pulaski J,Trivedi BK,Unangst PC,Xu X

    更新日期：2007-07-01 00:00:00

  • SAR profiles of spirocyclic nicotinamide derived selective HDAC1/HDAC2 inhibitors (SHI-1:2).

    abstract：:A potent family of spirocyclic nicotinyl aminobenzamide selective HDAC1/HDAC2 inhibitors (SHI-1:2) is profiled. The incorporation of a biaryl zinc-binding motif into a nicotinyl scaffold resulted in enhanced potency and selectivity versus HDAC3, but also imparted hERG activity. It was discovered that increasing polar ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.052

    authors： Methot JL,Hamblett CL,Mampreian DM,Jung J,Harsch A,Szewczak AA,Dahlberg WK,Middleton RE,Hughes B,Fleming JC,Wang H,Kral AM,Ozerova N,Cruz JC,Haines B,Chenard M,Kenific CM,Secrist JP,Miller TA

    更新日期：2008-12-01 00:00:00

  • Quantitating the concentration of Py-Im polyamide-fluorescein conjugates in live cells.

    abstract：:Quantitative fluorescence-based methods have been developed to determine the nuclear concentration of polyamide-fluorescein conjugates in cell culture. Confocal laser scanning microscopy and flow cytometry techniques are utilized to plot calibration curves, from which the nuclear concentration can be interpolated. Upo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.05.063

    authors： Hsu CF,Dervan PB

    更新日期：2008-11-15 00:00:00

  • 2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: Identification, stereochemistry and initial SAR.

    abstract：:This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.045

    authors： Wyatt PG,Allen MJ,Borthwick AD,Davies DE,Exall AM,Hatley RJ,Irving WR,Livermore DG,Miller ND,Nerozzi F,Sollis SL,Szardenings AK

    更新日期：2005-05-16 00:00:00

  • Redox-responsive and calcium-dependent switching of glycosyldisulfide interactions with Concanavalin A.

    abstract：:Glycosyldisulfides can interact efficiently with carbohydrate-binding entities. This has been shown for a range of thiosaccharide dimers when tested for their effects against the lectin Concanavalin A using a modified quartz crystal microbalance-technique. Contrary to the thiosaccharide monomers, showing no significan...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.04.024

    authors： Pei Z,Aastrup T,Anderson H,Ramström O

    更新日期：2005-06-02 00:00:00

  • Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities.

    abstract：:Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were m...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.10.035

    authors： Quang TH,Ngan NTT,Ko W,Kim DC,Yoon CS,Sohn JH,Yim JH,Kim YC,Oh H

    更新日期：2014-12-15 00:00:00

  • Minimum structural requirements for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s.

    abstract：:Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.03.033

    authors： Fujii K,Morita D,Onoda K,Kuroda T,Miyachi H

    更新日期：2016-05-01 00:00:00

  • Synthesis of novel chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives via domino aldol-type/hetero Diels-Alder reaction and their cytotoxicity evaluation.

    abstract：:New chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives have been synthesized by domino aldol-type reaction/hetero Diels-Alder reaction generated from o-quinone methide in situ from 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones with resorcinols/naphthols in the presenc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.08.005

    authors： Madda J,Venkatesham A,Naveen Kumar B,Nagaiah K,Sujitha P,Ganesh Kumar C,Rao TP,Jagadeesh Babu N

    更新日期：2014-09-15 00:00:00

  • Functional expression and characterization of EryA, the erythritol kinase of Brucella abortus, and enzymatic synthesis of L-erythritol-4-phosphate.

    abstract：:The eryA gene of the bacterial pathogen Brucella abortus has been functionally expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P). The steady state kinetic parameters of this reaction were determined and the enzyme was ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)01032-6

    authors： Lillo AM,Tetzlaff CN,Sangari FJ,Cane DE

    更新日期：2003-02-24 00:00:00

  • The role of phosphate in the action of thymidine phosphorylase inhibitors: Implications for the catalytic mechanism.

    abstract：:The design and synthesis of 5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil (AIFU), a potent inhibitor of thymidine phosphorylase (TP) with K(i)-values of 11nM (ecTP) and 17nM (hTP), are described. Kinetic studies established that the type of inhibition of TP by AIFU is uncompetitive with respect to inorganic phosphat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.01.076

    authors： Jain HV,Rasheed R,Kalman TI

    更新日期：2010-03-01 00:00:00

  • Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD).

    abstract：:Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodelin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.046

    authors： Wu Y,Li J,Wu J,Morgan P,Xu X,Rancati F,Vallese S,Raveglia L,Hotchandani R,Fuller N,Bard J,Cunningham K,Fish S,Krykbaev R,Tam S,Goldman SJ,Williams C,Mansour TS,Saiah E,Sypek J,Li W

    更新日期：2012-01-01 00:00:00

  • Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity.

    abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.083

    authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

    更新日期：2016-12-15 00:00:00

  • Attenuation of TNF-α secretion by L-proline-based cyclic dipeptides produced by culture broth of Pseudomonas aeruginosa.

    abstract：:To identify small molecule inhibitors of TNF-α, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.10.075

    authors： Khan R,Basha A,Goverdhanam R,Rao PC,Tanemura Y,Fujimoto Y,Begum AS

    更新日期：2015-12-15 00:00:00

  • 4-Substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with superior pharmacological and pharmacokinetic parameters.

    abstract：:A novel class of 4-substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu opioid receptor as well as the nociceptin/orp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.05.063

    authors： Alberati D,Hainzl D,Jolidon S,Kurt A,Pinard E,Thomas AW,Zimmerli D

    更新日期：2006-08-15 00:00:00

  • Lp-PLA2 inhibitory activities of fatty acid glycerols isolated from Saururus chinensis roots.

    abstract：:(R)-Glycerol-monolinoleate 4 and (R)-glycerol-monostearate 5 were isolated from the ethyl acetate extracts of Saururus chinensis roots and (R)- or (S)-fatty acid glycerols 4 and 5 were synthesized for confirming their structures and evaluating their inhibitory activities against Lp-PLA(2). The (R)-4 and (S)-4 exhibite...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.05.056

    authors： Lee WS,Kim MJ,Beck YI,Park YD,Jeong TS

    更新日期：2005-08-01 00:00:00