当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > N-substituted azaindoles as potent inhibitors of Cdc7 kinase.

N-substituted azaindoles as potent inhibitors of Cdc7 kinase.

Abstract：

:Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy. We have identified a class of Cdc7 inhibitors based on a substituted indole core. Synthesis of focused indole and azaindole analogs yielded potent and selective 5-azaindole Cdc7 inhibitors with improved intrinsic metabolic stability (ie 36). In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co-crystallography data, and allowed the design of 7-azaindole 37 as a second lead in this series.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Bryan MC,Falsey JR,Frohn M,Reichelt A,Yao G,Bartberger MD,Bailis JM,Zalameda L,Miguel TS,Doherty EM,Allen JG

doi

10.1016/j.bmcl.2013.02.007

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

2056-60

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00181-9

journal_volume

23

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • 4-[(8-Alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-diethylbenzamides: high affinity, selective ligands for the delta opioid receptor illustrate factors important to antagonist activity.

    abstract：:The tropane derived compounds, 4-[(8-alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-d iethylbenzamides (5a-d), were synthesized and found to have high affinity and selectivity for the delta receptor. Compounds 5a-d are structurally similar to the full agonist (-)-RTI-5989-54 (3); yet, efficacy studies for com...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00209-2

    authors： Thomas JB,Atkinson RN,Rothman RB,Burgess JP,Mascarella SW,Dersch CM,Xu H,Carroll FI

    更新日期：2000-06-05 00:00:00

  • Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17alpha-hydroxylase/17,20-lyase (P450(17alpha)).

    abstract：:We report the preliminary results of the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a number of phenyl alkyl imidazole-based compounds as inhibitors of the two components of 17alpha-hydroxylase/17,20-lyase (P450(17alpha)), that is, 17alpha-hydroxylase (17alpha-OHase) and 17,20-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.06.092

    authors： Patel CH,Dhanani S,Owen CP,Ahmed S

    更新日期：2006-09-15 00:00:00

  • Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives.

    abstract：:A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.01.039

    authors： Bahekar SS,Shinde DB

    更新日期：2004-04-05 00:00:00

  • Structure-activity relationships of neuropeptide Y Y1 receptor antagonists related to BIBP 3226.

    abstract：:Analogues of BIBP 3226, (R)-N(alpha)-diphenylacetyl-N-(4-hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity. Combination with a N(G)...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00292-4

    authors： Aiglstorfer I,Hendrich I,Moser C,Bernhardt G,Dove S,Buschauer A

    更新日期：2000-07-17 00:00:00

  • Flavonoids: structural requirements for antiproliferative activity on breast cancer cells.

    abstract：:Several classes of flavonoids (flavones, flavanones, 2'-hydroxychalcones and flavan-4-ols) having a variety of substituents on A ring were investigated for their antiproliferative activity against MCF-7 human breast cancer cells. Structure-activity relationships of these compounds were discussed. 2'-hydroxychalcones a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00617-5

    authors： Pouget C,Lauthier F,Simon A,Fagnere C,Basly JP,Delage C,Chulia AJ

    更新日期：2001-12-17 00:00:00

  • Glycan multivalency effects toward albumin enable N-glycan-dependent tumor targeting.

    abstract：:Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing ∼10 molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in B...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.03.046

    authors： Ogura A,Tahara T,Nozaki S,Onoe H,Kurbangalieva A,Watanabe Y,Tanaka K

    更新日期：2016-05-01 00:00:00

  • 4-Aryl-2-anilinopyrimidines as corticotropin-releasing hormone (CRH) antagonists.

    abstract：:A series of 4-aryl-2-(N-ethylanilino)pyrimidines has been synthesized as corticotropin-releasing hormone (CRH) inhibitors. The effect of substitution on each aromatic ring on receptor binding was investigated. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00132-8

    authors： Cocuzza AJ,Hobbs FW,Arnold CR,Chidester DR,Yarem JA,Culp S,Fitzgerald L,Gilligan PJ

    更新日期：1999-04-05 00:00:00

  • Discovery of 5-substituted-N-arylpyridazinones as inhibitors of p38 MAP kinase.

    abstract：:The synthesis, structure-activity relationship and modeling of a series of 5-substituted-N-aryl pyridazinone based p38alpha inhibitors are described. In comparing the series to the similar N-aryl pyridinone series, it was found that the pyridazinones maintained a weaker interaction to the p38 enzyme, and therefore sho...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.03.088

    authors： Jerome KD,Hepperle ME,Walker JK,Xing L,Devraj RV,Benson AG,Baldus JE,Selness SR

    更新日期：2010-05-15 00:00:00

  • Synthesis, structural properties and insulin-enhancing potential of bis(quercetinato)oxovanadium(IV) conjugate.

    abstract：:An oxovanadium complex of quercetin (2), exhibits highly potent insulin-enhancing activity in streptozotocin-induced diabetic mice. It also mimics mitogenic potential of insulin as evaluated by [H(3)]thymidine uptake assay making an effective, orally active insulin-enhancing agent for the treatment of both type 1 and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.020

    authors： Shukla R,Barve V,Padhye S,Bhonde R

    更新日期：2004-10-04 00:00:00

  • Adamantyl-tethered-biphenylic compounds induce apoptosis in cancer cells by targeting Bcl homologs.

    abstract：:Bcl homologs prominently contribute to apoptotic resistance in cancer cells and serve as molecular targets in treatment of various cancers. Herein, we report the synthesis of biphenyl-adamantane derivatives by a ligand free palladium on carbon based Suzuki reaction using diisopropylamine as a base for the coupling of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.12.026

    authors： Anusha S,Mohan CD,Ananda H,Baburajeev CP,Rangappa S,Mathai J,Fuchs JE,Li F,Shanmugam MK,Bender A,Sethi G,Basappa,Rangappa KS

    更新日期：2016-02-01 00:00:00

  • New highly active taxoids from 9beta-dihydrobaccatin-9,10-acetals. Part 3.

    abstract：:We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00891-0

    authors： Takeda Y,Yoshino T,Uoto K,Chiba J,Ishiyama T,Iwahana M,Jimbo T,Tanaka N,Terasawa H,Soga T

    更新日期：2003-01-20 00:00:00

  • 3,4-Dihydro-1-isoquinolinamines: a novel class of nitric oxide synthase inhibitors with a range of isoform selectivity and potency.

    abstract：:3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00119-6

    authors： Beaton H,Hamley P,Nicholls DJ,Tinker AC,Wallace AV

    更新日期：2001-04-23 00:00:00

  • Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists.

    abstract：:Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel co...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.12.088

    authors： Büttelmann B,Peters JU,Ceccarelli S,Kolczewski S,Vieira E,Prinssen EP,Spooren W,Schuler F,Huwyler J,Porter RH,Jaeschke G

    更新日期：2006-04-01 00:00:00

  • A new quinoline derivative with cytotoxic activity from Streptomyces sp. neau50.

    abstract：:A new quinoline derivative, methyl 8-(3-methoxy-3-methylbutyl)-2-methylquinoline-4-carboxylate (1), was isolated from the endophytic strain Streptomyces sp. neau50, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human lung adenocarcinoma cell line A549 with...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.095

    authors： Wang XJ,Gong DL,Wang JD,Zhang J,Liu CX,Xiang WS

    更新日期：2011-04-15 00:00:00

  • Design and synthesis of potent HIV-1 protease inhibitors incorporating hydroxyprolinamides as novel P2 ligands.

    abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different hydroxyprolinamide P2 ligands were designed and synthesized. Variation of substitutions at the P2 significantly affected the enzyme inhibitory potency of the inhibitors. Compounds 2a and 2d showed excellent enzyme inhibitory activi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.070

    authors： Gao BL,Zhang CM,Yin YZ,Tang LQ,Liu ZP

    更新日期：2011-06-15 00:00:00

  • Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells.

    abstract：:We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.03.054

    authors： Ronco C,Millet A,Plaisant M,Abbe P,Hamouda-Tekaya N,Rocchi S,Benhida R

    更新日期：2017-05-15 00:00:00

  • The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist.

    abstract：:The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropiset...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00670-3

    authors： Macor JE,Gurley D,Lanthorn T,Loch J,Mack RA,Mullen G,Tran O,Wright N,Gordon JC

    更新日期：2001-02-12 00:00:00

  • Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes.

    abstract：:The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure as central template for nonpeptide RGD mim...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00216-5

    authors： Pandey A,Seroogy J,Volkots D,Smyth MS,Rose J,Mehrotra MM,Heath J,Ruhter G,Schotten T,Scarborough RM

    更新日期：2001-05-21 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 mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling.

    abstract：:A series of anilinonicotinyl linked pyrazolo[1,5-a]pyrimidine conjugates (6a-x) were synthesized and evaluated for their antiproliferative activity. Some of these conjugates exhibited promising cytotoxic effects in the MCF-7 cell line and among these 6a and 6c exhibited significant effects, apart from G2/M cell cycle ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.02.072

    authors： Kamal A,Faazil S,Hussaini SM,Ramaiah MJ,Balakrishna M,Patel N,Pushpavalli SN,Pal-Bhadra M

    更新日期：2016-04-15 00:00:00

  • Enzymatic syntheses of 6-(4H-selenolo[3,2-b]pyrrolyl)-L-alanine, 4-(6H-selenolo[2,3-b]pyrrolyl)-L-alanine, and 6-(4H-furo[3,2-b]pyrrolyl-L-alanine.

    abstract：:6-(4H-Selenolo[3,2-b]pyrrolyl)-L-alanine 1, 4-(6H-selenolo[2,3-b]pyrrolyl)-L-alanine 2, and 6-(4H-furo[3,2-b]pyrrolyl)-L-alanine 3 have been synthesized via reactions of selenolo[3,2-b]pyrrole, selenolo[2,3-b]pyrrole, and furo[3,2-b]pyrrole, respectively, with L-serine. The reactions are catalyzed by Salmonella typhim...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00067-0

    authors： Welch M,Phillips RS

    更新日期：1999-03-08 00:00:00

  • Inhibition of Src kinase activity by 4-anilino-7-thienyl-3-quinolinecarbonitriles.

    abstract：:Based on a screening lead from a yeast-based assay to identify Src family kinase inhibitors, a series of 4-anilino-7-thienyl-3-quinolinecarbonitriles was prepared. When the thiophene ring was substituted with a water-solubilizing group in a 2,5-, 3,5- or 2,4-pattern, potent inhibition of Src kinase activity was observ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00302-5

    authors： Boschelli DH,Wang DY,Ye F,Yamashita A,Zhang N,Powell D,Weber J,Boschelli F

    更新日期：2002-08-05 00:00:00

  • Synthesis and cytotoxic activity of A-ring modified betulinic acid derivatives.

    abstract：:New A-ring modified betulinic acid derivatives having small steric hindrance were prepared and tested for cytotoxic activity on 3 cancer cell lines: 10 compounds showed stronger cytotoxic activity than betulinic acid. Especially, the compounds bearing 1-ene-3-oxo with electron-withdrawing groups at C2 showed strong cy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00724-8

    authors： You YJ,Kim Y,Nam NH,Ahn BZ

    更新日期：2003-10-06 00:00:00

  • Design, synthesis, and cytostatic activity of novel cyclic curcumin analogues.

    abstract：:A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.07.079

    authors： Youssef D,Nichols CE,Cameron TS,Balzarini J,De Clercq E,Jha A

    更新日期：2007-10-15 00:00:00

  • Design, syntheses, and evaluation of Taspase1 inhibitors.

    abstract：:Taspase1 is a threonine protease responsible for cleaving MLL (Mixed-Lineage Leukemia) to achieve proper HOX gene expression. Subsequent studies identified additional Taspase1 substrates including Transcription Factor IIA (TFIIA) and Drosophila HCF. Taspase1 is essential for cell proliferation and is overexpressed in ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.07.045

    authors： Lee JT,Chen DY,Yang Z,Ramos AD,Hsieh JJ,Bogyo M

    更新日期：2009-09-01 00:00:00

  • Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy.

    abstract：:Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.05.055

    authors： Nishiura Y,Matsumura A,Kobayashi N,Shimazaki A,Sakamoto S,Kitade N,Tonomura Y,Ino A,Okuno T

    更新日期：2018-08-01 00:00:00

  • Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14.

    abstract：:The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-04-159-2, a potent, covalent CDK14 inhibitor with a TAIRE kinase ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.05.024

    authors： Ferguson FM,Doctor ZM,Ficarro SB,Marto JA,Kim ND,Sim T,Gray NS

    更新日期：2019-08-01 00:00:00

  • Fluorine-18 labeled galactosylated chitosan for asialoglycoprotein-receptor-mediated hepatocyte imaging.

    abstract：:Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [(18)F]FB-GC was obtained w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.106

    authors： Yang W,Mou T,Guo W,Jing H,Peng C,Zhang X,Ma Y,Liu B

    更新日期：2010-08-15 00:00:00

  • Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.

    abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127456

    authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

    更新日期：2020-10-01 00:00:00

  • Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: identification of novel peptidic inhibitors.

    abstract：:MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.04.094

    authors： Noguchi T,Oishi S,Honda K,Kondoh Y,Saito T,Kubo T,Kaneda M,Ohno H,Osada H,Fujii N

    更新日期：2013-07-01 00:00:00