当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2.

Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2.

Abstract：

:Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC50=0.086 μM). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Wang W,Lv D,Qiu N,Zhang L,Hu C,Hu Y

doi

10.1016/j.bmc.2013.03.070

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

2886-94

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00292-7

journal_volume

21

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • A laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity.

    abstract：:Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.028

    authors： Wellington KW,Kolesnikova NI

    更新日期：2012-07-15 00:00:00

  • Further optimization of sulfonamide analogs as EP1 receptor antagonists: synthesis and evaluation of bioisosteres for the carboxylic acid group.

    abstract：:4-{[2-[(2-Furylsulfonyl)(isobutyl)amino]-5-(trifluoromethyl)phenoxy]methyl}benzoic acid analogs 2a and b and a series of the acid analogs, in which the carboxylic acid residue of 2b was replaced with various kinds of carboxylic acid bioisosteres, were synthesized and evaluated as EP1 receptor antagonists. Compound 2b ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.06.067

    authors： Naganawa A,Matsui T,Ima M,Saito T,Murota M,Aratani Y,Kijima H,Yamamoto H,Maruyama T,Ohuchida S,Nakai H,Toda M

    更新日期：2006-11-01 00:00:00

  • Chemiluminescence flow sensor for berberine with immobilized reagents.

    abstract：:A sensitive chemiluminescence (CL) sensor for berberine combined with flow-injection (FI) technology is described. The analytical reagents involved in the CL reaction, including luminol and potassium ferricyanide, were both immobilized on an anion-exchange resin column. While a volume of sodium phosphate was passed th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00069-4

    authors： Song Z,Zhao T,Wang L,Xiao Z

    更新日期：2001-07-01 00:00:00

  • Cytotoxic palladium complexes of bioreductive quinoxaline N1,N4-dioxide prodrugs.

    abstract：:Four new palladium(II) complexes with the formula Pd(L)(2), where L are quinoxaline-2-carbonitrile N(1),N(4)-dioxide derivatives, were synthesized as a contribution to the chemistry and pharmacology of metal compounds with this class of pharmacologically interesting bioreductive prodrugs. Compounds were characterized ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.12.064

    authors： Urquiola C,Vieites M,Torre MH,Cabrera M,Lavaggi ML,Cerecetto H,González M,Cerain AL,Monge A,Smircich P,Garat B,Gambino D

    更新日期：2009-02-15 00:00:00

  • Tyrenes: synthesis of new antiproliferative compounds with an extended conjugation.

    abstract：:A series of substituted styryl-acrylonitriles was designed and synthesized. The new compounds, called tyrenes, were tested for the ability to inhibit acute lymphocytic leukemia (ALL) cancer cell growth, as well as on their toxicity to normal bone marrow (NBM) cells. The results showed that 3,4-dihydroxystyryl-acryloni...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.03.043

    authors： Demin P,Rounova O,Grunberger T,Cimpean L,Sharfe N,Roifman CM

    更新日期：2004-06-01 00:00:00

  • Synthesis and preliminary in vivo evaluation of new [18F]fluoro-inositols as Positron Emission Tomography radiotracers.

    abstract：:This study describes the synthesis and radiosynthesis of eight new [18F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.e. O-alkylated inositols, or on the cyclo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.08.035

    authors： Collet C,Schmitt S,Maskali F,Clément A,Chrétien F,Karcher G,Marie PY,Poussier S,Lamandé-Langle S

    更新日期：2017-10-15 00:00:00

  • Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents.

    abstract：:As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-p...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.09.041

    authors： Lai YY,Huang LJ,Lee KH,Xiao Z,Bastow KF,Yamori T,Kuo SC

    更新日期：2005-01-03 00:00:00

  • New analogs of SYA013 as sigma-2 ligands with anticancer activity.

    abstract：:Our previous study has revealed 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one·2HCl (SYA013) 1 as a sigma ligand with moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.04.012

    authors： Asong G,Zhu XY,Bricker B,Andey T,Amissah F,Lamango N,Ablordeppey SY

    更新日期：2019-06-15 00:00:00

  • Toward protein-cleaving catalytic drugs: artificial protease selective for myoglobin.

    abstract：:A protein-cleaving catalyst highly selective for a disease-related protein can be used as a catalytic drug. As the first protein-cleaving catalyst selective for a protein substrate, a catalyst for myoglobin (Mb) was designed by attaching the Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinato...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00216-5

    authors： Jeon JW,Son SJ,Yoo CE,Hong IS,Suh J

    更新日期：2003-07-03 00:00:00

  • Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″ binding site.

    abstract：:On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1″ hydrophobic specificity pocket. This report details ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.07.025

    authors： Nara H,Sato K,Naito T,Mototani H,Oki H,Yamamoto Y,Kuno H,Santou T,Kanzaki N,Terauchi J,Uchikawa O,Kori M

    更新日期：2014-10-01 00:00:00

  • Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.

    abstract：:A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.025

    authors： Holler JG,Slotved HC,Mølgaard P,Olsen CE,Christensen SB

    更新日期：2012-07-15 00:00:00

  • Molecular structure and stereoelectronic properties of herbicide sulphonylureas.

    abstract：:MO theoretical calculations were used with the aim to investigate the electronic properties of a number of sulphonylureas 1-8 which are employed as antifeedants. Quantum chemical descriptors [electron density, molecular electrostatic potential (MEP), the topology of frontier orbitals and reactivity index] were determi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00357-1

    authors： Galeazzi R,Marucchini C,Orena M,Zadra C

    更新日期：2002-04-01 00:00:00

  • Effect of single pyrrole replacement with β-alanine on DNA binding affinity and sequence specificity of hairpin pyrrole/imidazole polyamides targeting 5'-GCGC-3'.

    abstract：:N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that can recognize predetermined DNA sequences with high sequence specificity. As many eukaryotic promoter regions contain highly GC-rich sequences, it is valuable to synthesize and characterize Py-Im polyamides that recognize GC-rich m...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.06.005

    authors： Han YW,Kashiwazaki G,Morinaga H,Matsumoto T,Hashiya K,Bando T,Harada Y,Sugiyama H

    更新日期：2013-09-01 00:00:00

  • QSAR of the testosterone binding globulin affinity by means of correlation weighting of local invariants of the graph of atomic orbitals.

    abstract：:Numerical values of the testosterone binding globulin affinity have been modeled as a mathematical function of molecular structure in two versions of molecular structure elucidation: first, by hydrogen-filled molecular graphs (HFG); second, by the so-called graphs of atomic orbitals (GAO). Increased orders of Morgan e...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.07.059

    authors： Raska I Jr,Toropov A

    更新日期：2005-12-15 00:00:00

  • Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors.

    abstract：:Targeted polypharmacology provides an efficient method of treating diseases such as cancer with complex, multigenic causes provided that compounds with advantageous activity profiles can be discovered. Novel covalent TAK1 inhibitors were validated in cellular contexts for their ability to inhibit the TAK1 kinase and f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.11.034

    authors： Tan L,Gurbani D,Weisberg EL,Jones DS,Rao S,Singer WD,Bernard FM,Mowafy S,Jenney A,Du G,Nonami A,Griffin JD,Lauffenburger DA,Westover KD,Sorger PK,Gray NS

    更新日期：2017-02-15 00:00:00

  • Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors.

    abstract：:Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is a...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.09.017

    authors： Thangavelu B,Bhansali P,Viola RE

    更新日期：2015-10-15 00:00:00

  • New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity.

    abstract：:Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2,3-dehydrosilybin deriva...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.01.035

    authors： Dzubák P,Hajdúch M,Gazák R,Svobodová A,Psotová J,Walterová D,Sedmera P,Kren V

    更新日期：2006-06-01 00:00:00

  • Enzymatic resolution of racemates with a 'remote' stereogenic center as an efficient tool in drug, flavor and vitamin synthesis.

    abstract：:The enantioselective recognition of 'remote' stereogenic centers represents a scientific task in organic chemistry being also of current interest in the pharmaceutical industry. This is due to a range of pharmaceutically relevant molecules or intermediates thereof bearing a stereogenic center, which is separated from ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmc.2014.06.024

    authors： Alfaro Blasco M,Gröger H

    更新日期：2014-10-15 00:00:00

  • Inhibitory effect of beta-diketones and their metal complexes on TNF-alpha induced expression of ICAM-1 on human endothelial cells.

    abstract：:Recent reports show that the natural beta-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of beta-diketone compounds, which are curcumi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.07.064

    authors： Caruso F,Pettinari C,Marchetti F,Rossi M,Opazo C,Kumar S,Balwani S,Ghosh B

    更新日期：2009-09-01 00:00:00

  • Tryptophan-based fluorophores for studying protein conformational changes.

    abstract：:With the continuing interest in deciphering the interplay between protein function and conformational changes, small fluorescence probes will be especially useful for tracking changes in the crowded protein interior space. Presently, we describe the potential utility of six unnatural amino acid fluorescence donors str...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.09.015

    authors： Talukder P,Chen S,Liu CT,Baldwin EA,Benkovic SJ,Hecht SM

    更新日期：2014-11-01 00:00:00

  • Synthesis and DNA binding studies of a new asymmetric cyanine dye binding in the minor groove of [poly(dA-dT)]2.

    abstract：:A new asymmetric cyanine dye has been synthesised and its interaction with different DNA has been investigated. In this dye, BEBO, the structure of the known intercalating cyanine dye BO has been extended with a benzothiazole substituent. The resulting crescent-shape of the molecule is similar to that of the well-know...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00463-7

    authors： Karlsson HJ,Lincoln P,Westman G

    更新日期：2003-03-20 00:00:00

  • Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors.

    abstract：:A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.09.004

    authors： Zhu L,Luo K,Li K,Jin Y,Lin J

    更新日期：2017-11-01 00:00:00

  • Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy.

    abstract：:Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an impo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.04.033

    authors： He J,Li D,Xiong K,Ge Y,Jin H,Zhang G,Hong M,Tian Y,Yin J,Zeng H

    更新日期：2012-06-15 00:00:00

  • Synthesis and anticonvulsant activity of new N-Mannich bases derived from 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones. Part II.

    abstract：:Synthesis and anticonvulsant activity of new N-Mannich bases of 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones have been described. Initial anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.032

    authors： Obniska J,Rzepka S,Kamiński K

    更新日期：2012-08-01 00:00:00

  • Synthesis and biological evaluation of methoxyphenyl porphyrin derivatives as potential photodynamic agents.

    abstract：:A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro-4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was fo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00138-9

    authors： Milanesio ME,Morán FS,Yslas EI,Alvarez MG,Rivarola V,Durantini EN

    更新日期：2001-08-01 00:00:00

  • Towards the first inhibitors of trihydroxynaphthalene reductase from Curvularia lunata: synthesis of artificial substrate, homology modelling and initial screening.

    abstract：:Trihydroxynaphthalene reductase (3HNR) is an essential enzyme in the biosynthesis of fungal melanin and it represents an emerging target for the development of new fungicides and antimicotics. To promote the discovery of new inhibitors, an improved chemical synthesis of the artificial substrate 2,3-dihydro-2,5-dihydro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.04.066

    authors： Brunskole M,Stefane B,Zorko K,Anderluh M,Stojan J,Lanisnik Rizner T,Gobec S

    更新日期：2008-06-01 00:00:00

  • 4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.

    abstract：:A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.07.040

    authors： Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期：2018-08-15 00:00:00

  • Structural optimization and in vitro profiling of N-phenylbenzamide-based farnesoid X receptor antagonists.

    abstract：:Activation of the nuclear farnesoid X receptor (FXR) which acts as cellular bile acid sensor has been validated as therapeutic strategy to counter liver disorders such as non-alcoholic steatohepatitis by the clinical efficacy of obeticholic acid. FXR antagonism, in contrast, is less well studied and potent small molec...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.07.017

    authors： Schmidt J,Schierle S,Gellrich L,Kaiser A,Merk D

    更新日期：2018-08-07 00:00:00

  • Synthesis of new arylalkoxy amido derivatives as melatoninergic ligands.

    abstract：:Amido derivatives 10-18 of the corresponding oxyamines were synthesised as melatoninergic ligands by the reaction of hydroxyphtalimide with the halogeno derivatives or the corresponding alcohols using Mitsunobu reaction conditions. The affinity of the compounds for chicken brain melatonin receptors and recombinant hum...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00328-0

    authors： Pégurier C,Morellato L,Chahed E,Andrieux J,Nicolas JP,Boutin JA,Bennejean C,Delagrange P,Langlois M,Mathé-Allainmat M

    更新日期：2003-03-06 00:00:00

  • Synthesis and anti-inflammatory activity of isoquebecol.

    abstract：:We report here the synthesis of isoquebecol, an unprecedented constitutional isomer of quebecol, a polyphenolic compound discovered in maple syrup. The methodology used to prepare isoquebecol involves, as key steps, the formation of a dibromoalkene from an α-ketoester precursor, followed by a double Suzuki-Miyaura rea...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.01.050

    authors： Cardinal S,Paquet-Côté PA,Azelmat J,Bouchard C,Grenier D,Voyer N

    更新日期：2017-04-01 00:00:00