当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery and optimization of a series of liver X receptor antagonists.

Discovery and optimization of a series of liver X receptor antagonists.

Abstract：

:The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Jiao X,Kopecky DJ,Fisher B,Piper DE,Labelle M,McKendry S,Harrison M,Jones S,Jaen J,Shiau AK,Escaron P,Danao J,Chai A,Coward P,Kayser F

doi

10.1016/j.bmcl.2012.07.048

subject

Has Abstract

pub_date

2012-09-15 00:00:00

pages

5966-70

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00924-9

journal_volume

22

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • A highly atom economic, chemo-, regio- and stereoselective synthesis and evaluation of spiro-pyrrolothiazoles as antitubercular agents.

    abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolothiazoles chemo-, regio- and stereoselectively in quantitative yields. These compounds w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.107

    authors： Karthikeyan SV,Bala BD,Raja VP,Perumal S,Yogeeswari P,Sriram D

    更新日期：2010-01-01 00:00:00

  • Synthesis, biophysical and biological evaluation of 3,6-bis-amidoacridines with extended 9-anilino substituents as potent G-quadruplex-binding telomerase inhibitors.

    abstract：:Telomerase and telomere maintenance are emerging targets for the treatment of human cancers. We report here on the targeting of the telomere-telomerase complex with a series of small molecules based on an acridine platform. A series of 3,6-bisamidoacridines with extended 9-anilino sidechains were designed and synthesi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.05.090

    authors： Schultes CM,Guyen B,Cuesta J,Neidle S

    更新日期：2004-08-16 00:00:00

  • Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists.

    abstract：:Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.07.023

    authors： Ando M,Sekino E,Haga Y,Moriya M,Ito M,Ito J,Iwaasa H,Ishihara A,Kanatani A,Ohtake N

    更新日期：2009-09-01 00:00:00

  • Parallel solid-phase synthesis of a model library of 7alpha-alkylamide estradiol derivatives as potential estrogen receptor antagonists.

    abstract：:The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00487-4

    authors： Tremblay MR,Simard J,Poirier D

    更新日期：1999-10-04 00:00:00

  • Synthesis of enamino-2-oxindoles via conjugate addition between α-azido ketones and 3-alkenyl oxindoles: Cytotoxicity evaluation and apoptosis inducing studies.

    abstract：:A facile method for the construction of double bond between 3-ylidene oxindoles and α-azido ketones has been successfully accomplished with a mild base. This method features azido reduction with concomitant double bond formation to provide the new class of bioactive enamino-2-oxindoles. These new compounds were screen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.07.038

    authors： Kumar NP,Vanjari Y,Thatikonda S,Pooladanda V,Sharma P,Sridhar B,Godugu C,Kamal A,Shankaraiah N

    更新日期：2018-12-01 00:00:00

  • P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K.

    abstract：:An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, s...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.05.062

    authors： Barrett DG,Boncek VM,Catalano JG,Deaton DN,Hassell AM,Jurgensen CH,Long ST,McFadyen RB,Miller AB,Miller LR,Payne JA,Ray JA,Samano V,Shewchuk LM,Tavares FX,Wells-Knecht KJ,Willard DH Jr,Wright LL,Zhou HQ

    更新日期：2005-08-01 00:00:00

  • Effects of alkyl parabens on plant pathogenic fungi.

    abstract：:Alkyl parabens are used as antimicrobial preservatives in cosmetics, food, and pharmaceutical products. However, the mode of action of these chemicals has not been assessed thoroughly. In this study, we determined the effects of alkyl parabens on plant pathogenic fungi. All the fungi tested, were susceptible to parabe...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.02.049

    authors： Ito S,Yazawa S,Nakagawa Y,Sasaki Y,Yajima S

    更新日期：2015-04-15 00:00:00

  • Calcitonin gene-related peptide (CGRP) receptor antagonists: pyridine as a replacement for a core amide group.

    abstract：:In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Som...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.02.065

    authors： Luo G,Chen L,Civiello R,Pin SS,Xu C,Kostich W,Kelley M,Conway CM,Macor JE,Dubowchik GM

    更新日期：2012-04-15 00:00:00

  • Carbazolothiophene-2-carboxylic acid derivatives as endothelin receptor antagonists.

    abstract：:The SmI(2)-promoted three-component coupling reaction of thiophene-2-carboxylate, indole-2-carbaldehyde and acetophenone provides an expedient route to a series of tetracyclic carbazolothiophene compounds bearing the indole and thiophene rings. Among these samples, 9-benzyl-4-methyl-4-(4-hydroxyphenyl)-10-oxo-4,10-dih...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.067

    authors： Babu G,Yu HM,Yang SM,Fang JM

    更新日期：2004-03-08 00:00:00

  • Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoprotein.

    abstract：:Installation of a C2-aminopropyl side chain to the 2,4-diaryl-2,5-dihydropyrrole series of kinesin spindle protein (KSP) inhibitors results in potent, water soluble compounds, but the aminopropyl group induces susceptibility to cellular efflux by P-glycoprotein (Pgp). We show that by carefully modulating the basicity ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.03.006

    authors： Cox CD,Breslin MJ,Whitman DB,Coleman PJ,Garbaccio RM,Fraley ME,Zrada MM,Buser CA,Walsh ES,Hamilton K,Lobell RB,Tao W,Abrams MT,South VJ,Huber HE,Kohl NE,Hartman GD

    更新日期：2007-05-15 00:00:00

  • New diterpene furanoids from the Antarctic lichen Huea sp.

    abstract：:In the course of ongoing research on protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from Antarctic lichens, four new diterpene furanoids, hueafuranoids A-D (1-4) have been isolated from the MeOH extract of Antarctic lichen Huea sp. by various chromatographic methods. The structures of these compounds wer...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.10.063

    authors： Cui Y,Yim JH,Lee DS,Kim YC,Oh H

    更新日期：2012-12-15 00:00:00

  • Identification of lead small molecule inhibitors of glycogen synthase kinase-3 beta using a fragment-linking strategy.

    abstract：:Glycogen synthase kinase-3 beta (GSK3β) kinase serves as a promising therapeutic target for the treatment of various human diseases, such as diabetes, obesity, and Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.060

    authors： Kim J,Moon Y,Hong S

    更新日期：2016-12-01 00:00:00

  • The discovery of 3-(N-alkyl)aminopropylphosphonic acids as potent S1P receptor agonists.

    abstract：:3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.04.069

    authors： Hale JJ,Doherty G,Toth L,Li Z,Mills SG,Hajdu R,Ann Keohane C,Rosenbach M,Milligan J,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala S

    更新日期：2004-07-05 00:00:00

  • Identification of free fatty acid receptor 2 agonists using virtual screening.

    abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127460

    authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

    更新日期：2020-11-01 00:00:00

  • Design of novel alpha7-subtype-preferring nicotinic acetylcholine receptor agonists: application of docking and MM-PBSA computational approaches, synthetic and pharmacological studies.

    abstract：:In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric alpha7 channels, we carried out the virtual screening of a test set of potential nicotinic ligands, and adopted a simplified MM-PBSA approach to estimate their relative binding free energy values. By means ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.073

    authors： Grazioso G,Pomè DY,Matera C,Frigerio F,Pucci L,Gotti C,Dallanoce C,De Amici M

    更新日期：2009-11-15 00:00:00

  • New p-terphenyls from the endophytic fungus Aspergillus sp. YXf3.

    abstract：:Five new p-terphenyls named prenylterphenyllin D (1), prenylterphenyllin E (2), 2'-O-methylprenylterphenyllin (3), 4-O-methylprenylterphenyllin (4) and 3'-O-methylterphenyllin (5) together with seven known compounds (6-12), were isolated from cultures of Aspergillus sp. YXf3. The structures of the new compounds were e...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.11.033

    authors： Yan W,Wuringege,Li SJ,Guo ZK,Zhang WJ,Wei W,Tan RX,Jiao RH

    更新日期：2017-01-01 00:00:00

  • Inhibition of lysosomal cysteine proteases by chrysotherapeutic compounds: a possible mechanism for the antiarthritic activity of Au(I).

    abstract：:Although Au(I) complexes have been used to treat rheumatoid arthritis for over 75 years, their mechanism of action is still poorly understood. A family of enzymes responsible for joint destruction in rheumatoid arthritis, the cathepsins, has been discussed as a possible biological target of Au(I). In this study, inhib...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.073

    authors： Chircorian A,Barrios AM

    更新日期：2004-10-18 00:00:00

  • Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain.

    abstract：:A series of new voltage-gated sodium channel blockers were prepared based on the screening lead succinic diamide BPBTS. Replacement of the succinimide linker with the more rigid cyclic 1,2-trans-diamide linker was well tolerated. N-Methylation on the biphenylsulfonamide side of the amide moiety significantly reduced t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.002

    authors： Shao PP,Ok D,Fisher MH,Garcia ML,Kaczorowski GJ,Li C,Lyons KA,Martin WJ,Meinke PT,Priest BT,Smith MM,Wyvratt MJ,Ye F,Parsons WH

    更新日期：2005-04-01 00:00:00

  • Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. Part 6: further focus on the contracted C4'-side chain analogues.

    abstract：:Novel benzo[b]thiophene diamine thrombin inhibitors were investigated, focusing on a contracted C4'-side chain series. SAR studies identified compounds with either a pyrrolidino or morpholino group as potent, active site directed thrombin inhibitors when the amino group was connected to the C3-phenyl ring with a methy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00211-0

    authors： Takeuchi K,Kohn TJ,Harper RW,Lin HS,Gifford-Moore DS,Richett ME,Sall DJ,Smith GF,Zhang M

    更新日期：2000-06-05 00:00:00

  • A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I.

    abstract：:The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistanc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.08.121

    authors： More SS,Vince R

    更新日期：2006-12-01 00:00:00

  • 4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators.

    abstract：:Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent ac...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.036

    authors： Xiong H,Brugel TA,Balestra M,Brown DG,Brush KA,Hightower C,Hinkley L,Hoesch V,Kang J,Koether GM,McCauley JP Jr,McLaren FM,Panko LM,Simpson TR,Smith RW,Woods JM,Brockel B,Chhajlani V,Gadient RA,Spear N,Sygowski LA

    更新日期：2010-12-15 00:00:00

  • QSAR study on the affinity of some arylpiperazines towards the 5-HT1A/alpha1-adrenergic receptor using the E-state index.

    abstract：:QSAR models represent the relationship of biological activity with either physicochemical parameters or structural indices. QSAR study was performed on some arylpiperazines as 5-HT(1A)/alpha(1)-adrenergic receptor antagonists using E-state indices to identify the pharmacophoric requirements. It was found that some of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00598-5

    authors： Debnath B,Samanta S,Naskar SK,Roy K,Jha T

    更新日期：2003-09-01 00:00:00

  • Opsin shift in an aldolase antibody.

    abstract：:An antibody-retinal assembly that mimics the opsin shift (OS) of the naturally occurring visual pigments is reported. Both experiments and calculations show that the aldolase antibody 33F12 covalently binds all-trans retinal via a protonated Schiff base with a lysine residue. This chromophore, which exhibits a remarka...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00406-0

    authors： Grynszpan F,Keinan E

    更新日期：1999-08-16 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

  • Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity.

    abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.083

    authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

    更新日期：2016-12-15 00:00:00

  • Synthesis and antifungal activity of the 2,2,5-tetrahydrofuran regioisomers of SCH 51048.

    abstract：:The four 2,2,5-regioisomer counterparts of SCH 51048 were synthesized and evaluated. As with the parent series, only the two cis isomers possessed any in vitro activity, and only the activity of the isomer with the R-configuration at the tetrahydrofuran 2-carbon was significant. The activity data suggests that oxygen ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00282-2

    authors： Lovey RG,Saksena AK,Girijavallabhan VM,Blundell P,Guzik H,Loebenberg D,Parmegiani RM,Cacciapuoti A

    更新日期：2002-07-08 00:00:00

  • Pyrazoles, 1,2,4-triazoles, and tetrazoles as surrogates for cis-amide bonds in boronate ester thrombin inhibitors.

    abstract：:Substituted pyrazoles, 1,2,4-triazoles, and tetrazoles are good surrogates for cis-amide bonds in a series of boronate ester thrombin inhibitors. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00104-8

    authors： Duncia JV,Santella JB 3rd,Higley CA,VanAtten MK,Weber PC,Alexander RS,Kettner CA,Pruitt JR,Liauw AY,Quan ML,Knabb RM,Wexler RR

    更新日期：1998-04-07 00:00:00

  • Oxidative burst inhibition, cytotoxicity and antibacterial acriquinoline alkaloids from Citrus reticulate (Blanco).

    abstract：:Two novel acridone-quinoline alkaloids, acriquinoline A (1) and acriquinoline B (2), together with twenty-two known compounds were isolated from the methanol extract of the root of Citrus reticulata Blanco. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR and mass spectr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.12.028

    authors： Fomani M,Ngeufa Happi E,Nouga Bisoue A,Ndom JC,Kamdem Waffo AF,Sewald N,Wansi JD

    更新日期：2016-01-15 00:00:00

  • Hydroxyl radicals scavenging activity of N-substituted chitosan and quaternized chitosan.

    abstract：:N-substituted chitosan and quaternized chitosan were synthesized and their antioxidant activity against hydroxyl radicals was assessed, respectively. Compared with the antioxidant activity of chitosan, the results indicated that the two kinds of chitosan derivatives had different scavenging ability on hydroxyl radical...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.09.009

    authors： Guo Z,Liu H,Chen X,Ji X,Li P

    更新日期：2006-12-15 00:00:00

  • In vitro antitubercular and antimicrobial activities of 1-substituted quinoxaline-2,3(1H,4H)-diones.

    abstract：:1-((Substituted)methyl)quinoxaline-2,3(1H,4H)-dione (2a-e) and 1-((substituted)acryloyl)quinoxaline-2,3(1H,4H)-dione (4a-c) were synthesized from quinoxaline-2,3(1H,4H)-dione 1 and evaluated for their antimicrobial activities. Results of the antitubercular screening against Mycobacterium tuberculosis H(37)Rv showed th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.026

    authors： Ramalingam P,Ganapaty S,Rao ChB

    更新日期：2010-01-01 00:00:00