当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery and structure-activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2.

Discovery and structure-activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2.

Abstract：

:We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Fuchi N,Iura Y,Kaneko H,Nitta A,Suyama K,Ueda H,Yamaguchi S,Nishimura K,Fujii S,Sekiya Y,Yamada M,Takahashi T

doi

10.1016/j.bmcl.2012.05.006

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

4358-61

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00596-3

journal_volume

22

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Novel highly potent mu-opioid receptor antagonist based on endomorphin-2 structure.

    abstract：:The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modification into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [d-2-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.01.009

    authors： Fichna J,do-Rego JC,Janecki T,Staniszewska R,Poels J,Broeck JV,Costentin J,Schiller PW,Janecka A

    更新日期：2008-02-15 00:00:00

  • Synthesis of a high-mannose-type glycopeptide analog containing a glucose-asparagine linkage.

    abstract：:The title compound was prepared by enzymatic transfer of oligosaccharide to a synthetic pentapeptide containing the Glc-Asn linkage. The compound was not hydrolyzed by glycoamidases from plant and bacterial sources, but it inhibited both enzymes in the micromolar range. Its activity is compared to other potential inhi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00306-0

    authors： Deras IL,Takegawa K,Kondo A,Kato I,Lee YC

    更新日期：1998-07-07 00:00:00

  • 1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro.

    abstract：:A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening reve...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.02.040

    authors： Cheng P,Huang N,Jiang ZY,Zhang Q,Zheng YT,Chen JJ,Zhang XM,Ma YB

    更新日期：2008-04-01 00:00:00

  • The development of benzo- and naphtho-fused quinoline-2,4-dicarboxylic acids as vesicular glutamate transporter (VGLUT) inhibitors reveals a possible role for neuroactive steroids.

    abstract：:Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic aci...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.086

    authors： Carrigan CN,Patel SA,Cox HD,Bolstad ES,Gerdes JM,Smith WE,Bridges RJ,Thompson CM

    更新日期：2014-02-01 00:00:00

  • Synthesis of trans-caffeate analogues and their bioactivities against HIV-1 integrase and cancer cell lines.

    abstract：:Forty caffeate analogues were synthesized via a convenient method starting from vanillin with moderate to good yields. The testing of biological activity of these compounds against HIV-1 integrase indicates that four compounds: bornyl caffeate, bornyl 2-nitrocaffeate, 5-nitrocaffeic acid and 5-nitrocaffeic acid phenet...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.046

    authors： Xia CN,Li HB,Liu F,Hu WX

    更新日期：2008-12-15 00:00:00

  • Identification of quinones as HER2 inhibitors for the treatment of trastuzumab resistant breast cancer.

    abstract：:HER2 overexpression is associated with aggressive breast cancer with high recurrence rate and poor patient prognosis. Treatment of HER2 overexpressing patients with the HER2 targeting therapy trastuzumab results in acquired resistance within a year. The HER2/EGFR dual kinase inhibitor lapatinib was shown to inhibit so...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.11.064

    authors： Sridhar J,Sfondouris ME,Bratton MR,Nguyen TL,Townley I,Klein Stevens CL,Jones FE

    更新日期：2014-01-01 00:00:00

  • Nav1.7 inhibitors for the treatment of chronic pain.

    abstract：:The voltage gated sodium channel Nav1.7 plays an essential role in the transmission of pain signals. Strong human genetic validation has motivated extensive efforts to discover potent, selective, and efficacious Nav1.7 inhibitors for the treatment of chronic pain. This digest will introduce the structure and function ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2018.08.007

    authors： McKerrall SJ,Sutherlin DP

    更新日期：2018-10-15 00:00:00

  • Design, synthesis and antitumor activity of non-camptothecin topoisomerase I inhibitors.

    abstract：:Three groups of non-camptothecin compounds with four to five fused rings have been designed and synthesized. Their in vitro anti-proliferative activity has been evaluated with five different cancer cell lines (HCT116, PC3, U87MG, HepG2, SK-OV-3). Compounds B-2 and B-3 showed the most potent cell growth inhibition with...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.06.042

    authors： Zhang C,Li S,Ji L,Liu S,Li Z,Li S,Meng X

    更新日期：2015-10-15 00:00:00

  • Synthesis and biological activity of trans-2,3-dihydroraloxifene.

    abstract：:The synthesis and biological evaluation of trans-2,3-dihydroraloxifene, 2, is described. The synthesis proceeds in 8 steps in 20% overall yield. Relative trans 2,3-stereochemistry is definitively established in ester 6, which is converted to the title compound via derivatization, Grignard addition, and deprotection. E...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00145-6

    authors： Schmid CR,Glasebrook AL,Misner JW,Stephenson GA

    更新日期：1999-04-19 00:00:00

  • Synthesis and preliminary evaluation of a new fluorine-18 labelled triazine derivative for PET imaging of cannabinoid CB2 receptor.

    abstract：:Cannabinoid CB2 PET tracers are considered as a promising alternative to PBR/TSPO tracers for the in-vivo imaging of neuroinflammation. We describe here the synthesis and characterization of compound 3, a new potent and brain penetrating CB2 ligand based on an original triazine template. The PET tracer [(18)F]-dideute...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.11.023

    authors： Hortala L,Arnaud J,Roux P,Oustric D,Boulu L,Oury-Donat F,Avenet P,Rooney T,Alagille D,Barret O,Tamagnan G,Barth F

    更新日期：2014-01-01 00:00:00

  • Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties.

    abstract：:A new series of Proteolysis Targeting Chimeras (PROTACs) targeting Bruton's Tyrosine Kinase (BTK) was synthesized, with the goal of improving the pharmacokinetic properties of our previously reported PROTAC, MT802. We recently described the ability of MT802 to induce degradation of both wild-type and C481S mutant BTK ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126877

    authors： Jaime-Figueroa S,Buhimschi AD,Toure M,Hines J,Crews CM

    更新日期：2020-02-01 00:00:00

  • Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5'-ribofuran-uronamide moiety.

    abstract：:The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'-(N,N-d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.10.054

    authors： Gao ZG,Joshi BV,Klutz AM,Kim SK,Lee HW,Kim HO,Jeong LS,Jacobson KA

    更新日期：2006-02-01 00:00:00

  • N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter.

    abstract：:A series of glutathione derivatives 1-4, modified at the N,S and/or COOH sites, with in vitro antitrypanosomal activity were tested against bloodstream form Trypanosoma brucei 247 wild type and a T. b. brucei 247 strain over-expressing the multiple drug resistance protein (MRPA) by 50-100x to assess the susceptibility...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.05.086

    authors： Alibu VP,Daunes S,D'Silva C

    更新日期：2013-08-01 00:00:00

  • Structure-activity relationships of untenone A and its derivatives for inhibition of DNA polymerases.

    abstract：:We found that untenone A and mannzamenone A inhibit mammalian DNA polymerases alpha and beta, and human terminal deoxynucleotidyl transferase (TdT). The syntheses of both compounds and the structure-activity relationships of untenone A derivatives are described. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.01.092

    authors： Saito F,Takeuchi R,Kamino T,Kuramochi K,Sugawara F,Sakaguchi K,Kobayashi S

    更新日期：2004-04-19 00:00:00

  • Synthesis and evaluation of GGPP geometric isomers: divergent substrate specificities of FTase and GGTase I.

    abstract：:A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00292-x

    authors： Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

    更新日期：2001-06-18 00:00:00

  • 2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors.

    abstract：:A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo γ-secretase activity were identified and described. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.09.057

    authors： Parker MF,Barten DM,Bergstrom CP,Bronson JJ,Corsa JA,Dee MF,Gai Y,Guss VL,Higgins MA,Keavy DJ,Loo A,Mate RA,Marcin LR,McElhone KE,Polson CT,Roberts SB,Macor JE

    更新日期：2012-11-15 00:00:00

  • Discovery of novel, orally active dual NK1/NK2 antagonists.

    abstract：:Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2 antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2 receptors, with high-affinity (K(i)=0.12 and 0.62nM, respectively). In functi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00572-8

    authors： Bernstein PR,Aharony D,Albert JS,Andisik D,Barthlow HG,Bialecki R,Davenport T,Dedinas RF,Dembofsky BT,Koether G,Kosmider BJ,Kirkland K,Ohnmacht CJ,Potts W,Rumsey WL,Shen L,Shenvi A,Sherwood S,Stollman D,Russell K

    更新日期：2001-10-22 00:00:00

  • Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

    abstract：:We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.09.015

    authors： Sagar SR,Agarwal JK,Pandya DH,Dash RP,Nivsarkar M,Vasu KK

    更新日期：2015-10-15 00:00:00

  • Solid-phase parallel synthesis of azarene pyrrolidinones as factor Xa inhibitors.

    abstract：:A focused library (4 x 14) prepared from 4-aminopyridine and 4-, 5-, and 6-azoindole templates was synthesized using 14 polymer supported 4-amido-2,3,5,6-tetrafluorophenyl (TFP) sulfonate esters inputs. Several compounds were identified as factor Xa inhibitors (IC50< or =0.1 microM) helping to establish the SAR among ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00151-7

    authors： Gong Y,Becker M,Choi-Sledeski YM,Davis RS,Salvino JM,Chu V,Brown KD,Pauls HW

    更新日期：2000-05-15 00:00:00

  • Opioids and efflux transporters. Part 4: influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues.

    abstract：:The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demons...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.033

    authors： Metcalf MD,Rosicky AD,Hassan HE,Eddington ND,Coop A,Cunningham CW,Mercer SL

    更新日期：2014-08-01 00:00:00

  • Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 2: structure-activity relationships (SAR) of the C3-phenyl moiety.

    abstract：:Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identifica...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.03.074

    authors： Fader LD,Landry S,Goulet S,Morin S,Kawai SH,Bousquet Y,Dion I,Hucke O,Goudreau N,Lemke CT,Rancourt J,Bonneau P,Titolo S,Amad M,Garneau M,Duan J,Mason S,Simoneau B

    更新日期：2013-06-01 00:00:00

  • Evaluation of nitroalkenes as nitric oxide donors.

    abstract：:Chemiluminescence experiments demonstrate that simple nitroalkenes release low levels of nitric oxide. UV and EPR measurements suggest but cannot confirm direct NO release from nitroalkenes. Given the biological activity of nitrated unsaturated fatty acids, these results suggest the possible metabolic conversion of ni...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.01.016

    authors： Gorczynski MJ,Huang J,Lee H,King SB

    更新日期：2007-04-01 00:00:00

  • Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles.

    abstract：:The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2'-methoxyphenyl)-benzylidene)-5-bromo-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]-1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.002

    authors： Wood ER,Kuyper L,Petrov KG,Hunter RN 3rd,Harris PA,Lackey K

    更新日期：2004-02-23 00:00:00

  • Synthesis and cytotoxicity of (-)-renieramycin G analogs.

    abstract：:(-)-Renieramycin G and fifteen C-22 analogs were prepared employing l-tyrosine as the chiral starting material. These analogs, along with (-)-renieramycin G itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, A2780, MCF-7, A549, BGC-823, Ketr3, KB, Hela cells. The IC(50) values of most of these a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.025

    authors： Liu W,Dong W,Liao X,Yan Z,Guan B,Wang N,Liu Z

    更新日期：2011-03-01 00:00:00

  • Potent and highly selective kappa opioid receptor agonists incorporating chroman- and 2,3-dihydrobenzofuran-based constraints.

    abstract：:Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.08.094

    authors： Chu GH,Gu M,Cassel JA,Belanger S,Graczyk TM,DeHaven RN,Conway-James N,Koblish M,Little PJ,DeHaven-Hudkins DL,Dolle RE

    更新日期：2005-12-01 00:00:00

  • Syntheses and biological evaluations of alpha-D-mannosyl [60]fullerenols.

    abstract：:[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglut...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00583-2

    authors： Kato H,Yashiro A,Mizuno A,Nishida Y,Kobayashi K,Shinohara H

    更新日期：2001-11-19 00:00:00

  • Non-electrophilic modulators of the canonical Keap1/Nrf2 pathway.

    abstract：:Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2015.04.019

    authors： Richardson BG,Jain AD,Speltz TE,Moore TW

    更新日期：2015-06-01 00:00:00

  • 1-[4-(1H-Benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea derivatives as small molecule heparanase inhibitors.

    abstract：:A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.09.069

    authors： Pan W,Miao HQ,Xu YJ,Navarro EC,Tonra JR,Corcoran E,Lahiji A,Kussie P,Kiselyov AS,Wong WC,Liu H

    更新日期：2006-01-15 00:00:00

  • Folate pro-drug of cystamine as an enhanced treatment for nephropathic cystinosis.

    abstract：:Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transpor...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.048

    authors： Omran Z,Kay G,Hector EE,Knott RM,Cairns D

    更新日期：2011-04-15 00:00:00

  • Studies on the novel anti-staphyloccal compound nematophin.

    abstract：:A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00331-0

    authors： Kennedy G,Viziano M,Winders JA,Cavallini P,Gevi M,Micheli F,Rodegher P,Seneci P,Zumerle A

    更新日期：2000-08-07 00:00:00