当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions.

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions.

Abstract：

:As a continuation of our efforts to discover and develop the apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of 4-aryl-4H-chromenes with modifications at the 7- and 5-, 6-, 8-positions. It was found that a small hydrophobic group, such as NMe2, NH2, NHEt, and OMe, is preferred at the 7-position. Di-substitution at either the 5,7-positions or the 6,7-positions generally led to a large decrease in potency. Di-substitution at the 7,8-positions, in general, was found to result in potent compounds. 7-NMe2, 7-NHEt, 7-OMe, and 7,8-di-NH2 analogs were found to have similar SAR for the 4-aryl group, and several 7-substituted and 7,8-di-substituted analogs were found to have similar potencies as the lead compound MX58151 (2a) both as caspase activators and inhibitors of cell proliferation.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Kemnitzer W,Kasibhatla S,Jiang S,Zhang H,Zhao J,Jia S,Xu L,Crogan-Grundy C,Denis R,Barriault N,Vaillancourt L,Charron S,Dodd J,Attardo G,Labrecque D,Lamothe S,Gourdeau H,Tseng B,Drewe J,Cai SX

doi

10.1016/j.bmcl.2005.07.066

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

4745-51

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(05)00977-7

journal_volume

15

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • 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

  • Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure.

    abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00163-2

    authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

    更新日期：1998-05-05 00:00:00

  • Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells.

    abstract：:A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Prelimina...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.09.032

    authors： Liu YR,Luo JZ,Duan PP,Shao J,Zhao BX,Miao JY

    更新日期：2012-11-15 00:00:00

  • Effect of structural modification on the inhibitory selectivity of rutaecarpine derivatives on human CYP1A1, CYP1A2, and CYP1B1.

    abstract：:Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00469-4

    authors： Don MJ,Lewis DF,Wang SY,Tsai MW,Ueng YF

    更新日期：2003-08-04 00:00:00

  • Synthesis and evaluation of biotinylated sansalvamide A analogs and their modulation of Hsp90.

    abstract：:Described are the syntheses of three sansalvamide A derivatives that contain biotinylated tags at individual positions around the macrocycle. The tagged derivatives indicated in protein pull-down assays that they bind to Hsp90 at the same binding site (N-Middle domain) as the San A-amide peptide. Further, these compou...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.06.083

    authors： Kunicki JB,Petersen MN,Alexander LD,Ardi VC,McConnell JR,McAlpine SR

    更新日期：2011-08-15 00:00:00

  • Recent encounters with atropisomerism in drug discovery.

    abstract：:Atropisomerism is stereochemistry arising from restricted bond rotation that creates a chiral axis. Atropisomers are subject to time-dependent inversion of chirality via bond rotation, a property which in drug molecules introduces complexity and challenges for drug discovery and development processes. Greater recognit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2017.11.050

    authors： Glunz PW

    更新日期：2018-01-15 00:00:00

  • Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase.

    abstract：:A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubsti...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.08.114

    authors： Gopalsamy A,Aplasca A,Ciszewski G,Park K,Ellingboe JW,Orlowski M,Feld B,Howe AY

    更新日期：2006-01-15 00:00:00

  • Identification and optimisation of a series of substituted 5-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

    abstract：:Further investigation of a series of thienyl-based hydroxamic acids that included ADS100380 and ADS102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.10.045

    authors： Price S,Bordogna W,Braganza R,Bull RJ,Dyke HJ,Gardan S,Gill M,Harris NV,Heald RA,van den Heuvel M,Lockey PM,Lloyd J,Molina AG,Roach AG,Roussel F,Sutton JM,White AB

    更新日期：2007-01-15 00:00:00

  • Structure-activity relationships of novel potent MurF inhibitors.

    abstract：:A novel class of MurF inhibitors was discovered and structure-activity relationship studies have led to several potent compounds with IC(50)=22 approximately 70 nM. Unfortunately, none of these potent MurF inhibitors exhibited significant antibacterial activity even in the presence of bacterial cell permeabilizers. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.09.073

    authors： Gu YG,Florjancic AS,Clark RF,Zhang T,Cooper CS,Anderson DD,Lerner CG,McCall JO,Cai Y,Black-Schaefer CL,Stamper GF,Hajduk PJ,Beutel BA

    更新日期：2004-01-05 00:00:00

  • Thieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDK1 inhibitors discovered by fragment-based screening.

    abstract：:Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity agains...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.080

    authors： Lee AC,Ramanujulu PM,Poulsen A,Williams M,Blanchard S,Ma DM,Bonday Z,Goh KL,Goh KC,Goh MK,Wood J,Dymock BW

    更新日期：2012-06-15 00:00:00

  • Synthesis of sub-micromolar inhibitors of MraY by exploring the region originally occupied by the diazepanone ring in the liposidomycin structure.

    abstract：:The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00109-9

    authors： Dini C,Didier-Laurent S,Drochon N,Feteanu S,Guillot JC,Monti F,Uridat E,Zhang J,Aszodi J

    更新日期：2002-04-22 00:00:00

  • Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells.

    abstract：:A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Comp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.109

    authors： Su B,Chen S

    更新日期：2009-12-01 00:00:00

  • Facile synthesis and 18F-radiolabeling of α4β1-specific LLP2A-aryltrifluoroborate peptidomimetic conjugates.

    abstract：:The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, 111In-SPECT, and 64Cu- and 68Ga-PET im...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.08.011

    authors： Walker D,Li Y,Roxin Á,Schaffer P,Adam MJ,Perrin DM

    更新日期：2016-10-15 00:00:00

  • New polyphenols active on beta-amyloid aggregation.

    abstract：:New polyphenol classes have been tested against amyloid-beta peptide aggregation. We have identified four novel polyphenols which could be efficient fibril inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides B and D. We suggest that molecules with the particular C(6)-linkers-C(6) structure...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.11.028

    authors： Rivière C,Richard T,Vitrac X,Mérillon JM,Valls J,Monti JP

    更新日期：2008-01-15 00:00:00

  • AzaHx, a novel fluorescent, DNA minor groove and G·C recognition element: Synthesis and DNA binding properties of a p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (azaHx-PI) polyamide.

    abstract：:The design, synthesis, and DNA binding properties of azaHx-PI or p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (5) are described. AzaHx, 2-(p-anisyl)-4-aza-benzimidazole-5-carboxamide, is a novel, fluorescent DNA recognition element, derived from Hoechst 33258 to recognize G·C base pairs. Supported by theoretical dat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.06.055

    authors： Satam V,Babu B,Patil P,Brien KA,Olson K,Savagian M,Lee M,Mepham A,Jobe LB,Bingham JP,Pett L,Wang S,Ferrara M,Bruce CD,Wilson WD,Lee M,Hartley JA,Kiakos K

    更新日期：2015-09-01 00:00:00

  • Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

    abstract：:Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for ass...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.11.011

    authors： Han C,Chatterjee A,Noetzel MJ,Panarese JD,Smith E,Chase P,Hodder P,Niswender C,Conn PJ,Lindsley CW,Stauffer SR

    更新日期：2015-01-15 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 triazolamers as active site inhibitors of HIV-1 protease.

    abstract：:Proteases typically recognize their peptide substrates in extended conformations. General approaches for designing protease inhibitors often consist of peptidomimetics that feature this conformation. Herein we discuss a combination of computational and experimental studies to evaluate the potential of triazole-linked ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.049

    authors： Jochim AL,Miller SE,Angelo NG,Arora PS

    更新日期：2009-11-01 00:00:00

  • Enantiomeric 3-deaza-1',6'-isoneplanocin and its 3-bromo analogue: Synthesis by the Ullmann reaction and their antiviral properties.

    abstract：:The 1',6'-isomer of neplanocin A possesses biological properties that have not been optimised through rationally conceived analogues. In that direction, this Letter reports the use of the Ullmann reaction to achieve enantiomeric 3-deaza-1',6'-isoneplanocin and 3-bromo-3-deaza-1',6'-isoneplanocin. These four compounds ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.12.061

    authors： Liu C,Chen Q,Schneller SW

    更新日期：2016-02-01 00:00:00

  • Enhanced estrogen receptor beta (ERβ) selectivity of fluorinated carborane-containing ER modulators.

    abstract：:We previously showed that fluorination of the carborane-containing selective estrogen receptor modulator (SERM) BE360 altered the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity. Here, we designed and synthesized a series of fluorinated carboranyl phenols as candidate ERβ-sel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.10.067

    authors： Ohta K,Ogawa T,Kaise A,Endo Y

    更新日期：2013-12-15 00:00:00

  • First insight into structure-activity relationships of selective meprin β inhibitors.

    abstract：:The astacin proteases meprin α and β are emerging drug targets for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease. However, there are only few inhibitors of both proteases reported to date. Starting from NNGH as lead structure, a detailed elaboration of the structure-activity rel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.04.012

    authors： Ramsbeck D,Hamann A,Schlenzig D,Schilling S,Buchholz M

    更新日期：2017-06-01 00:00:00

  • Discovery of anabaenopeptin 679 from freshwater algal bloom material: Insights into the structure-activity relationship of anabaenopeptin protease inhibitors.

    abstract：:Cyanobacteria possess a unique capacity for the production of structurally novel secondary metabolites compared to the biosynthetic abilities of other environmental prokaryotes such as bacteria of the genus Streptomyces. Two different strategies to explore cyanobacteria-derived natural products have been explored prev...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.09.008

    authors： Harms H,Kurita KL,Pan L,Wahome PG,He H,Kinghorn AD,Carter GT,Linington RG

    更新日期：2016-10-15 00:00:00

  • Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa.

    abstract：:The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00249-3

    authors： Cingolani GM,Di Stefano A,Mosciatti B,Napolitani F,Giorgioni G,Ricciutelli M,Claudi F

    更新日期：2000-06-19 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

  • Enhancing the activity of membrane remodeling epsin-peptide by trimerization.

    abstract：:Modulating the structural dynamics of biomembranes by inducing bilayer curvature and lipid packing defects has been highlighted as a practical tool to modify membrane-dependent cellular processes. Previously, we have reported on an amphipathic helical peptide derived from the N-terminal segment (residues 1-18, EpN18) ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127190

    authors： Hsu WY,Masuda T,Afonin S,Sakai T,Arafiles JVV,Kawano K,Hirose H,Imanishi M,Ulrich AS,Futaki S

    更新日期：2020-06-15 00:00:00

  • A practical deuterium-free NMR method for the rapid determination of 1-octanol/water partition coefficients of pharmaceutical agents.

    abstract：:A simple and rapid NMR method is described to determine the logP of pharmaceutical agents. This method is highly versatile and efficient, because it does not require the use of deuterated solvents or the addition of any internal/external standards to the sample. We demonstrate that logP can be accurately measured usin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.08.145

    authors： Mo H,Balko KM,Colby DA

    更新日期：2010-11-15 00:00:00

  • Identification of a novel RAMP-independent CGRP receptor antagonist.

    abstract：:Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both ra...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.09.056

    authors： Zartman CB,Bell IM,Gallicchio SN,Graham SL,Kane SA,Mallee JJ,Rutledge RZ,Salvatore CA,Vacca JP,Williams TM

    更新日期：2011-11-15 00:00:00

  • Antifungal trichothecene sesquiterpenes obtained from the culture broth of marine-derived Trichoderma cf. brevicompactum and their structure-activity relationship.

    abstract：:Two new trichothecene sesquiterpenes, trichobreols D (1) and E (2), were isolated from the culture broth of marine-derived Trichoderma cf. brevicompactum together with trichobreol A (3). The structures of 1 and 2 were assigned on the basis of their spectroscopic data. Compound 1 inhibited the growth of two yeast-like ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127375

    authors： Yamazaki H,Yagi A,Takahashi O,Yamaguchi Y,Saito A,Namikoshi M,Uchida R

    更新日期：2020-09-01 00:00:00

  • Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.

    abstract：:A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.037

    authors： Benoit AR,Schiaffo C,Salomon CE,Goodell JR,Hiasa H,Ferguson DM

    更新日期：2014-07-15 00:00:00

  • Discovery of potent, selective small molecule inhibitors of α-subtype of type III phosphatidylinositol-4-kinase (PI4KIIIα).

    abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.05.093

    authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

    更新日期：2015-08-15 00:00:00