当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

Abstract：

:Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Huang SC,Adhikari S,Afroze R,Brewer K,Calderwood EF,Chouitar J,England DB,Fisher C,Galvin KM,Gaulin J,Greenspan PD,Harrison SJ,Kim MS,Langston SP,Ma LT,Menon S,Mizutani H,Rezaei M,Smith MD,Zhang DM,Gould AE

doi

10.1016/j.bmcl.2016.01.049

subject

Has Abstract

pub_date

2016-02-15 00:00:00

pages

1156-60

issue

4

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30049-X

journal_volume

26

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi.

    abstract：:In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00180-2

    authors： Girault S,Davioud-Charvet E,Salmon L,Berecibar A,Debreu MA,Sergheraert C

    更新日期：1998-05-19 00:00:00

  • Design and synthesis of pyridin-2-ylmethylaminopiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication.

    abstract：:A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of α-glycoprotein were evaluated in rat and dog pharmacokinetics. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.09.133

    authors： Skerlj R,Bridger G,Zhou Y,Bourque E,McEachern E,Langille J,Harwig C,Veale D,Yang W,Li T,Zhu Y,Bey M,Baird I,Sartori M,Metz M,Mosi R,Nelson K,Bodart V,Wong R,Fricker S,Mac Farland R,Huskens D,Schols D

    更新日期：2011-12-01 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

  • Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.

    abstract：:Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and stru...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.04.073

    authors： Cheruvallath Z,Tang M,McBride C,Komandla M,Miura J,Ton-Nu T,Erikson P,Feng J,Farrell P,Lawson JD,Vanderpool D,Wu Y,Dougan DR,Plonowski A,Holub C,Larson C

    更新日期：2016-06-15 00:00:00

  • Enzymatic synthesis of labeled DNA by PCR using new fluorescent thymidine nucleotide analogue and superthermophilic KOD dash DNA polymerase.

    abstract：:Triphosphate of a new fluorescent labeled thymidine analogue was incorporated as a substrate for PCR using KOD Dash DNA polymerase forming the corresponding fluorescent labeled DNA which is useful for a DNA probe. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00111-7

    authors： Obayashi T,Masud MM,Ozaki AN,Ozaki H,Kuwahara M,Sawai H

    更新日期：2002-04-22 00:00:00

  • Heterocyclic sulfoxide and sulfone inhibitors of fatty acid amide hydrolase.

    abstract：:A novel series of heterocyclic sulfoxides and sulfones was prepared and examined as potential inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for inactivation of neuromodulating fatty acid amides including anandamide and oleamide. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.10.025

    authors： Du W,Hardouin C,Cheng H,Hwang I,Boger DL

    更新日期：2005-01-03 00:00:00

  • Synthesis and biological evaluation of novel tricyclic oxazine and oxazepine fused quinazolines. Part 2: Gefitinib analogs.

    abstract：:Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to gefitinib and erlotinib, compounds 1a-1h were found to demonstrate more potent antit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.08.007

    authors： Sun M,Zhao J,Chen X,Zong Z,Han J,Du Y,Sun H,Wang F

    更新日期：2016-10-01 00:00:00

  • Potassium channel blocking 1,2-bis(aryl)ethane-1,2-diamines active as antiarrhythmic agents.

    abstract：:Atrial fibrillation (AF) is a major cause of stroke, heart failure, sudden death and cardiovascular morbidity. The Kv1.5 potassium channel conducts the IKur current and has been demonstrated to be predominantly expressed in atrial versus ventricular tissue. Blockade of Kv1.5 has been proven to be an effective approach...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.03.006

    authors： Kajanus J,Antonsson T,Carlsson L,Jurva U,Pettersen A,Sundell J,Inghardt T

    更新日期：2019-05-15 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

  • Virtual screening and biochemical evaluation to identify new inhibitors of mammalian target of rapamycin (mTOR).

    abstract：:Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.081

    authors： Park H,Choe H,Hong S

    更新日期：2014-02-01 00:00:00

  • Inhibitors of HCV NS5B polymerase. Part 2: Evaluation of the northern region of (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid.

    abstract：:A novel series of non-nucleoside HCV NS5B polymerase inhibitors was prepared from a (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid template. Solution and solid phase analog synthesis focused on the northern region of the template combined with structure based design led to the discovery of several potent and or...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.106

    authors： Pfefferkorn JA,Nugent R,Gross RJ,Greene M,Mitchell MA,Reding MT,Funk LA,Anderson R,Wells PA,Shelly JA,Anstadt R,Finzel BC,Harris MS,Kilkuskie RE,Kopta LA,Schwende FJ

    更新日期：2005-06-02 00:00:00

  • Synthesis and biological properties of new 1beta-methylcarbapenems containing heteroaromatic thioether moiety.

    abstract：:The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00451-6

    authors： Shin KJ,Koo KD,Yoo KH,Kang YK,Park SW,Kim DJ

    更新日期：2001-09-03 00:00:00

  • Structural requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase.

    abstract：:Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in mela...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.09.024

    authors： Thanigaimalai P,Lee KC,Sharma VK,Joo C,Cho WJ,Roh E,Kim Y,Jung SH

    更新日期：2011-11-15 00:00:00

  • Quinol fatty alcohols as promoters of axonal growth.

    abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.02.041

    authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

    更新日期：2006-05-15 00:00:00

  • HY251, a novel cell cycle inhibitor isolated from Aralia continentalis, induces G1 phase arrest via p53-dependent pathway in HeLa cells.

    abstract：:This study was aimed to elucidate the novel structure of HY251 isolated from the roots of Aralia continentalis and to evaluate its detailed inhibition mechanisms on cell cycle progression in HeLa cells. The structure of HY251 was elucidated based on the interpretation of the NMR spectra, as 3-propyl-2-vinyl-1,2,3,3a,3...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.11.087

    authors： Oh HL,Lim H,Cho YH,Koh HC,Kim H,Lim Y,Lee CH

    更新日期：2009-02-01 00:00:00

  • Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta.

    abstract：:The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the act...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.045

    authors： Liu Y,Wu J,Weissig H,Betancort JM,Gai WZ,Leventhal PS,Patricelli MP,Samii B,Szardenings AK,Shreder KR,Kozarich JW

    更新日期：2008-11-15 00:00:00

  • Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies.

    abstract：:A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.06.053

    authors： Patil SR,Asrondkar A,Patil V,Sangshetti JN,Kalam Khan FA,Damale MG,Patil RH,Bobade AS,Shinde DB

    更新日期：2017-08-15 00:00:00

  • SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists.

    abstract：:A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomer...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.09.093

    authors： Gomez L,Hack MD,McClure K,Sehon C,Huang L,Morton M,Li L,Barrett TD,Shankley N,Breitenbucher JG

    更新日期：2007-12-01 00:00:00

  • Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors.

    abstract：:Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00893-4

    authors： Lim HS,Oh YS,Suh PG,Chung SK

    更新日期：2003-01-20 00:00:00

  • Structural and stereochemical requirements of the spiroketal group of hippuristanol for antiproliferative activity.

    abstract：:Hippuristanol is a natural product that has recently been shown to inhibit eukaryotic translation initiation and tumor cell proliferation. To investigate the structure and activity relationship of hippuristanol, we synthesized a series of analogs by expanding the size of its F ring and determined their effects on the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.03.093

    authors： Li W,Dang Y,Liu JO,Yu B

    更新日期：2010-05-15 00:00:00

  • Synthesis of Dolastatin 15 mimetic peptoids.

    abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00034-1

    authors： Schmitt J,Bernd M,Kutscher B,Kessler H

    更新日期：1998-02-17 00:00:00

  • Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel.

    abstract：:The search for novel, potent Kv1.5 blockers based on an anthranilic amide scaffold employing a pharmacophore-based virtual screening approach is described. The synthesis and structure-activity relationships (SAR) with respect to inhibition of the Kv1.5 channel are discussed. The most potent compounds display sub-micro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.03.057

    authors： Peukert S,Brendel J,Pirard B,Strübing C,Kleemann HW,Böhme T,Hemmerle H

    更新日期：2004-06-07 00:00:00

  • In silico multi-filter screening approaches for developing novel beta-secretase inhibitors.

    abstract：:A large database of chemical structures was screened for potential inhibitors of beta-secretase was carried out using in silico multi-filter techniques. Substructure screening, computer-aided ligand docking, binding free energy calculations, and partial interaction energy analyses were performed successively to identi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.011

    authors： Fujimoto T,Matsushita Y,Gouda H,Yamaotsu N,Hirono S

    更新日期：2008-05-01 00:00:00

  • Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability.

    abstract：:A novel class of 4-aryl-8-(2-hydroxy-2-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...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.05.058

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

    更新日期：2006-08-15 00:00:00

  • Structural hybridization as a facile approach to new drug candidates.

    abstract：:Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug com...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2020.127514

    authors： Sampath Kumar HM,Herrmann L,Tsogoeva SB

    更新日期：2020-12-01 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

  • Synthesis and evaluation of a novel series of indoloisoquinolines as small molecule anti-malarial leads.

    abstract：:A group of novel synthetic indoloisoquinolines was prepared and its potential as a novel series of small-molecule anti-malarial leads was assessed. The structure-activity relationship on variation of three distinct regions of chemical space was investigated. A lead compound was generated with an activity close to that...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.071

    authors： Horrocks P,Fallon S,Denman L,Devine O,Duffy LJ,Harper A,Meredith EL,Hasenkamp S,Sidaway A,Monnery D,Phillips TR,Allin SM

    更新日期：2012-02-15 00:00:00

  • 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part. II: Synthesis and pharmacological evaluation of oxime and acidic head group structural variations.

    abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and P...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.03.143

    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：2009-05-15 00:00:00

  • Selective oxidation of 5-hydroxymethylcytosine with micelle incarcerated oxidants to determine it at single base resolution.

    abstract：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.017

    authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

    更新日期：2015-12-15 00:00:00

  • Study on antitumor activities of the chrysin-chromene-spirooxindole on Lewis lung carcinoma C57BL/6 mice in vivo.

    abstract：:The our previous study synthesized the chrysin-chromene-spirooxindole hybrids 3, and further found compound 3e had good antitumor activity against A549 cells in vitro through multi-target co-regulation of the p53 signalling pathway to inhibit the proliferation of A549 cells. This study was designed to evaluate the ant...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127410

    authors： Zhang WH,Chen S,Liu XL,Bing-Lin,Liu XW,Zhou Y

    更新日期：2020-09-01 00:00:00