当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of 4-anilino α-carbolines as novel Brk inhibitors.

Discovery of 4-anilino α-carbolines as novel Brk inhibitors.

Abstract：

:Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy difficult, remains a great challenge for cancer treatment. Recently, breast tumor kinase (Brk) was discovered as novel and interesting target for a cancer therapy because Brk participates in both cell dysregulation and metastasis. We discovered 4-anilino substituted α-carboline compounds as a novel class of highly active Brk inhibitors. In the current work, structure-activity relationships are discussed including docking results obtained for 4-anilino α-carbolines. A first profiling of selective kinase inhibition and a proof of concept for the antiproliferative effects is demonstrated. These results qualify the compounds as a promising class of novel antitumor agents.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Mahmoud KA,Krug M,Wersig T,Slynko I,Schächtele C,Totzke F,Sippl W,Hilgeroth A

doi

10.1016/j.bmcl.2014.03.002

subject

Has Abstract

pub_date

2014-04-15 00:00:00

pages

1948-51

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00218-2

journal_volume

24

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Carbonic anhydrase inhibitors. Design of anticonvulsant sulfonamides incorporating indane moieties.

    abstract：:A series of aromatic sulfonamides incorporating indane moieties were prepared starting from commercially available 1- and 2-indanamine, and their activity as inhibitors of two carbonic anhydrase (CA, EC 4.2.1.1) isozymes, hCA I and II was studied. The new sulfonamides incorporating acetamido, 4-chloro-benzoyl, valproy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.09.061

    authors： Chazalette C,Masereel B,Rolin S,Thiry A,Scozzafava A,Innocenti A,Supuran CT

    更新日期：2004-12-06 00:00:00

  • 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part I: synthesis and pharmacological evaluation.

    abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic beta-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARalpha, PPARgamma and PPARbeta/(d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.01.067

    authors： Parmenon C,Guillard J,Caignard DH,Hennuyer N,Staels B,Audinot-Bouchez V,Boutin JA,Dacquet C,Ktorza A,Viaud-Massuard MC

    更新日期：2008-03-01 00:00:00

  • Discovery of peptidic miR-21 processing inhibitor by mirror image phage display: A novel method to generate RNA binding D-peptides.

    abstract：:A novel method to generate RNA binding D-peptide has been developed. To achieve the screening method, phage display was applied to "Mirrored" RNA (L-enantiomer of RNA). We have selected pre-miR21 as an initial screening target to demonstrate the method. The mirrored pre-miR-21 binding peptide sequences were successful...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.01.023

    authors： Sakamoto K,Otake K,Umemoto T

    更新日期：2017-02-15 00:00:00

  • Phosphonium-ammonium-based di-cationic ionic liquids as antibacterial over the ESKAPE group.

    abstract：:Emergence of antibioresistance is currently a major threat of public health worldwide. Hence there is an urge need of finding new antibacterial material. Herein, we report a simple and eco-friendly method to synthesize homo and heterodicationic ionic liquids based on quaternary phosphonium and ammonium salt. In order ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127389

    authors： Brunel F,Lautard C,Garzino F,Raimundo JM,Bolla JM,Camplo M

    更新日期：2020-09-15 00:00:00

  • Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

    abstract：:2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.03.104

    authors： Goto T,Shiina A,Yoshino T,Mizukami K,Hirahara K,Suzuki O,Sogawa Y,Takahashi T,Mikkaichi T,Nakao N,Takahashi M,Hasegawa M,Sasaki S

    更新日期：2013-06-01 00:00:00

  • Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity.

    abstract：:Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice. suggesting that 5k ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00128-1

    authors： Hanano T,Adachi K,Aoki Y,Morimoto H,Naka Y,Hisadome M,Fukuda T,Sumichika H

    更新日期：2000-05-01 00:00:00

  • The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds.

    abstract：:We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were foun...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00137-3

    authors： Ahmed S,James K,Owen CP,Patel CK,Sampson L

    更新日期：2002-05-06 00:00:00

  • Evaluation of a series of bicyclic CXCR2 antagonists.

    abstract：:The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antag...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.11.039

    authors： Walters I,Austin C,Austin R,Bonnert R,Cage P,Christie M,Ebden M,Gardiner S,Grahames C,Hill S,Hunt F,Jewell R,Lewis S,Martin I,David Nicholls,David Robinson

    更新日期：2008-01-15 00:00:00

  • Analogues of dealanylalahopcin are inhibitors of human HIF prolyl hydroxylases.

    abstract：:Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00149-5

    authors： Schlemminger I,Mole DR,McNeill LA,Dhanda A,Hewitson KS,Tian YM,Ratcliffe PJ,Pugh CW,Schofield CJ

    更新日期：2003-04-17 00:00:00

  • Pyridazines. Part 36: Synthesis and antiplatelet activity of 5-substituted-6-phenyl-3(2H)-pyridazinones.

    abstract：:A convenient and efficient palladium-catalysed retro-ene-assisted method has been developed to prepare a series of 5-substituted-6-phenyl-3(2H)-pyridazinones as potential antiplatelet drugs. The most active compounds were those that contain a 3-phenyl-3-oxo-propenyl fragment or a phenylthio group at position 5 of the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.11.009

    authors： Coelho A,Sotelo E,Fraiz N,Yáñez M,Laguna R,Cano E,Raviña E

    更新日期：2004-01-19 00:00:00

  • Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.

    abstract：:In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). A...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.04.060

    authors： Song ZL,Chen HL,Wang YH,Goto M,Gao WJ,Cheng PL,Morris-Natschke SL,Liu YQ,Zhu GX,Wang MJ,Lee KH

    更新日期：2015-07-01 00:00:00

  • Peptoids as endothelin receptor antagonists.

    abstract：:A series of new peptoids as endothelin receptor antagonists has been synthesized. Screening them for their ability to bind with endothelin receptors (ET(A) and ET(B)) competitively in the presence of (125I) endothelin led to the discovery of compounds as possible leads with IC50s in the low micromolar concentrations. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00009-9

    authors： Dasgupta F,Gangadhar N,Bruhaspathy M,Verma AK,Sarin S,Mukherjee AK

    更新日期：2001-02-26 00:00:00

  • Synthesis and biological evaluation of novel pyrazolo[3,4-b]pyridines as cis-restricted combretastatin A-4 analogues.

    abstract：:Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127025

    authors： Jian XE,Yang F,Jiang CS,You WW,Zhao PL

    更新日期：2020-04-15 00:00:00

  • Macrocyclic hexapeptide analogues of the thrombin receptor (PAR-1) activation motif SFLLRN.

    abstract：:The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and evaluated in vitro. In general, the compounds were much less potent in inducing platelet aggregati...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00731-8

    authors： McComsey DF,Hecker LR,Andrade-Gordon P,Addo MF,Maryanoff BE

    更新日期：1999-01-18 00:00:00

  • On the preparation of indoxyl red from indican and some new characteristics.

    abstract：:An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.12.006

    authors： Song J,Kitamatsu M,Imamura K,Ohmori H,Watanabe K,Nakanishi K

    更新日期：2013-02-01 00:00:00

  • Diaminocyclobutenediones as potent and orally bioavailable CXCR2 receptor antagonists: SAR in the phenolic amide region.

    abstract：:A series of potent and orally bioavailable 3,4-diaminocyclobutenediones with various amide modifications and substitution on the left side phenyl ring were prepared and found to show significant inhibitory activities towards both CXCR2 and CXCR1 receptors. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.05.049

    authors： Aki C,Chao J,Ferreira JA,Dwyer MP,Yu Y,Chao J,Merritt RJ,Lai G,Wu M,Hipkin RW,Fan X,Gonsiorek W,Fosseta J,Rindgen D,Fine J,Lundell D,Taveras AG,Biju P

    更新日期：2009-08-01 00:00:00

  • A novel series of metabotropic glutamate receptor 5 negative allosteric modulators based on a 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine core.

    abstract：:A series of potent non-acetylinic negative allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 NAMs) was developed starting from HTS screening hit 1. Potency was improved via iterative SAR, and physicochemical properties were optimized to deliver orally bioavailable compounds acceptable for in vivo t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.044

    authors： Duvey G,Perry B,Le Poul E,Poli S,Bonnet B,Lambeng N,Charvin D,Donovan-Rodrigues T,Haddouk H,Gagliardi S,Rocher JP

    更新日期：2013-08-15 00:00:00

  • 5-Propynylamino alpha-deoxyuridine promotes DNA duplex stabilization of anionic and neutral but not cationic alpha-oligonucleotides.

    abstract：:Incorporation of 5-propynylamino and 5-propynyl alpha-2'-deoxyuridine into alpha-oligonucleotides (alpha-ON) allows high-affinity targeting of complementary DNA for alpha-ON with anionic and neutral backbone but not for cationic alpha-ON, revealing clues on the role of the amino group of the propynylamino on the forma...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.052

    authors： Deglane G,Morvan F,Debart F,Vasseur JJ

    更新日期：2007-02-15 00:00:00

  • Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi.

    abstract：:Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) b...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.06.085

    authors： Miyata Y,Fujii H,Uenohara Y,Kobayashi S,Takeuchi T,Nagase H

    更新日期：2012-08-15 00:00:00

  • An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives via one-pot three-component reaction.

    abstract：:Novel fused 1H-benzo[f]chromen-indole derivatives were synthesized regioselectivly in good to high yields by triethyl amine catalyzed condensation of 3-cyanoacetylindoles, β-naphthol and aryl aldehydes in methanol under ultrasounic irradiations and conventional conditions. The easy work-up of the products, rapidity, a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.07.059

    authors： Hossein nia R,Mamaghani M,Tabatabaeian K,Shirini F,Rassa M

    更新日期：2012-09-15 00:00:00

  • Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors.

    abstract：:Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.06.031

    authors： Barnes-Seeman D,Boiselle C,Capacci-Daniel C,Chopra R,Hoffmaster K,Jones CT,Kato M,Lin K,Ma S,Pan G,Shu L,Wang J,Whiteman L,Xu M,Zheng R,Fu J

    更新日期：2014-08-15 00:00:00

  • 1,2,3-Thiadiazole thioacetanilides as a novel class of potent HIV-1 non-nucleoside reverse transcriptase inhibitors.

    abstract：:A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiaz...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.09.055

    authors： Zhan P,Liu X,Cao Y,Wang Y,Pannecouque C,De Clercq E

    更新日期：2008-10-15 00:00:00

  • Design of selective Cathepsin inhibitors.

    abstract：:A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.06.090

    authors： Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher S

    更新日期：2009-08-15 00:00:00

  • Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    abstract：:New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.054

    authors： Asano R,Nagami A,Fukumoto Y,Miura K,Yazama F,Ito H,Sakata I,Tai A

    更新日期：2014-03-01 00:00:00

  • Phosphinic acid-based inhibitors of tubulin polyglutamylases.

    abstract：:Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study descr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.05.069

    authors： Liu Y,Garnham CP,Roll-Mecak A,Tanner ME

    更新日期：2013-08-01 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

  • Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors.

    abstract：:Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.03.022

    authors： Chen Z,Wang ZC,Yan XQ,Wang PF,Lu XY,Chen LW,Zhu HL,Zhang HW

    更新日期：2015-05-01 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

  • Diamine preparation for synthesis of a water soluble Ni(II) salen complex.

    abstract：:A reliable and efficient synthesis of a Ni(II) salen complex useful in probing nucleic acid structure is described and illustrates a general approach for constructing cis diamines suitable for assembly into N2O2 Schiff base complexes. Two equivalents of an aryllithium reacted with 1,4-dimethylpiperazine-2,3-dione to f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00020-7

    authors： Shearer JM,Rokita SE

    更新日期：1999-02-08 00:00:00

  • Synthesis, characterization and preliminary analysis of in vivo biological activity of chitosan/celecoxib microcapsules.

    abstract：:The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules adminis...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.05.054

    authors： Cheng SY,Yuen MC,Lam PL,Gambari R,Wong RS,Cheng GY,Lai PB,Tong SW,Chan KW,Lau FY,Kok SH,Lam KH,Chui CH

    更新日期：2010-07-15 00:00:00