当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Identification of a new biaryl scaffold generating potent renin inhibitors.

Identification of a new biaryl scaffold generating potent renin inhibitors.

Abstract：

:The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar renin IC(50) and good oral bioavailability in rats.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lacombe P,Aspiotis R,Bayly C,Chen A,Dubé D,Fortin R,Gallant M,Juteau H,Liu S,McKay D,Roy P,Wu T

doi

10.1016/j.bmcl.2010.07.127

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

5822-6

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01096-6

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015-2019).

    abstract：:Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints and key transcriptional events in response to extracellular and intracellular signals leading to proliferation. Significant clinical activity for ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2019.126637

    authors： Sánchez-Martínez C,Lallena MJ,Sanfeliciano SG,de Dios A

    更新日期：2019-10-15 00:00:00

  • Design, synthesis and biological evaluation of a bivalent micro opiate and adenosine A1 receptor antagonist.

    abstract：:The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.112

    authors： Mathew SC,Ghosh N,By Y,Berthault A,Virolleaud MA,Carrega L,Chouraqui G,Commeiras L,Condo J,Attolini M,Gaudel-Siri A,Ruf J,Parrain JL,Rodriguez J,Guieu R

    更新日期：2009-12-01 00:00:00

  • Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp.

    abstract：:A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.062

    authors： Faria JV,dos Santos MS,Bernardino AM,Becker KM,Machado GM,Rodrigues RF,Canto-Cavalheiro MM,Leon LL

    更新日期：2013-12-01 00:00:00

  • Novel dual inhibitors of calpain and lipid peroxidation.

    abstract：:A series of molecules with dual inhibitory activities on calpain and lipid peroxidation were synthesized. These hybrid compounds were built on the calpain pharmacophore 2-hydroxytetrahydrofuran linked to a set of antioxidants via a l-leucine linker. Compound 7, the most potent in cellular calpain and lipid peroxidatio...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.04.105

    authors： Auvin S,Pignol B,Navet E,Pons D,Marin JG,Bigg D,Chabrier PE

    更新日期：2004-07-16 00:00:00

  • Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.

    abstract：:Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring form...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.03.062

    authors： Glunz PW,Cheng X,Cheney DL,Weigelt CA,Wei A,Luettgen JM,Wong PC,Wexler RR,Priestley ES

    更新日期：2015-01-01 00:00:00

  • Arylanthranilodinitriles: a new biaryl class of antileishmanial agents.

    abstract：:A series of anthranilodinitrile-based biaryls were synthesized and evaluated in vitro against extracellular promastigotes and intracellular amastigotes of Leishmania donovani. Among various screened compounds, a biaryl with trifluoromethyl group 5f showed 83% inhibition against promastigotes and 70% inhibition against...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.02.012

    authors： Singh FV,Vatsyayan R,Roy U,Goel A

    更新日期：2006-05-15 00:00:00

  • Discovery of highly potent and selective benzyloxybenzyl-based peroxisome proliferator-activator receptor (PPAR) delta agonists.

    abstract：:A series of 1,4-benzyloxybenzylsulfanylaryl carboxylic acids were prepared and their activities for PPAR receptor subtypes (alpha, delta, and gamma) with potential indications for the treatment of dyslipidemia were investigated. Analog 13a displayed the greatest binding affinity (IC(50)=10nM) and selectivity (120-fold...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.04.046

    authors： Bratton LD,Filzen GF,Geyer A,Hoffman JK,Lu G,Pulaski J,Trivedi BK,Unangst PC,Xu X

    更新日期：2007-07-01 00:00:00

  • Sulfamoyl benzamides as novel CB2 cannabinoid receptor ligands.

    abstract：:Sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Starting from a screening hit 8 that had modest affinity for the cannabinoid CB(2) receptor, a parallel synthesis approach and initial SAR are described, leading to compound 27 with 120-fold functional selectivity for the CB(2) rec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.006

    authors： Worm K,Zhou QJ,Saeui CT,Green RC,Cassel JA,Stabley GJ,DeHaven RN,Conway-James N,LaBuda CJ,Koblish M,Little PJ,Dolle RE

    更新日期：2008-05-01 00:00:00

  • Electrochemical and peroxidase oxidation study of N'-hydroxyguanidine derivatives as NO donors.

    abstract：:The electrochemical properties of a series of N-substituted-N'-hydroxyguanidines were studied. Two oxidation potentials of each compound were obtained by cyclic voltammetry. The E(ox1) values were from 0.51 to 0.62V, while the E(ox2) values were from 1.14 to 1.81V in acetonitrile solution. Next, their enzymatic contro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00185-3

    authors： Cai T,Xian M,Wang PG

    更新日期：2002-06-03 00:00:00

  • The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles.

    abstract：:Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126846

    authors： Reddyrajula R,Dalimba U

    更新日期：2020-01-15 00:00:00

  • Synthesis of 2'-O,4'-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase.

    abstract：:The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'-C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.04.050

    authors： Chapron C,Glen R,La Colla M,Mayes BA,McCarville JF,Moore S,Moussa A,Sarkar R,Seifer M,Serra I,Stewart A

    更新日期：2014-06-15 00:00:00

  • Carbonic anhydrase inhibitors: Selective inhibition of the extracellular, tumor-associated isoforms IX and XII over isozymes I and II with glycosyl-thioureido-sulfonamides.

    abstract：:A series of glycosyl-thioureido sulfonamides incorporating glucosamine, galactosamine, and mannosamine tails, and sulfanilamide, halogenosulfanilamide, and metanilamide heads was synthesized. Many of the new compounds showed micromolar-submicromolar affinity for the inhibition of the cytosolic isoforms I and II of the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.07.019

    authors： Smaine FZ,Winum JY,Montero JL,Regainia Z,Vullo D,Scozzafava A,Supuran CT

    更新日期：2007-09-15 00:00:00

  • Ligand binding cooperativity: Bioisosteric replacement of CO with SO2 among thrombin inhibitors.

    abstract：:Ligand-protein binding is a complex process that involves the formation of number of non-covalent interactions, e.g. H-bonds and hydrophobic interactions, between the ligand and the protein host. Upon binding, ligand functional groups can act synergistically (positive cooperativity) to improve the overall ligand bindi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.07.024

    authors： Said AM,Hangauer DG

    更新日期：2016-08-15 00:00:00

  • 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs.

    abstract：:Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This comp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.070

    authors： Kai H,Morioka Y,Koriyama Y,Okamoto K,Hasegawa Y,Hattori M,Koike K,Chiba H,Shinohara S,Iwamoto Y,Takahashi K,Tanimoto N

    更新日期：2008-12-15 00:00:00

  • Synthesis of novel orthoalkylaminophenol derivatives as potent neuroprotective agents in vitro.

    abstract：:A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00504-1

    authors： Larget R,Lockhart B,Pfeiffer B,Neudorffer A,Fleury MB,Largeron M

    更新日期：1999-10-18 00:00:00

  • Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.

    abstract：:Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00480-6

    authors： Llinàs-Brunet M,Bailey M,Déziel R,Fazal G,Gorys V,Goulet S,Halmos T,Maurice R,Poirier M,Poupart MA,Rancourt J,Thibeault D,Wernic D,Lamarre D

    更新日期：1998-10-06 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

  • 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

  • Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists.

    abstract：:Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.11.031

    authors： Meurer LC,Finke PE,Mills SG,Walsh TF,Toupence RB,Debenham JS,Goulet MT,Wang J,Tong X,Fong TM,Lao J,Schaeffer MT,Chen J,Shen CP,Sloan Stribling D,Shearman LP,Strack AM,Van der Ploeg LH

    更新日期：2005-02-01 00:00:00

  • Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.

    abstract：:The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.071

    authors： Qiao JX,Cheng X,Smallheer JM,Galemmo RA,Drummond S,Pinto DJ,Cheney DL,He K,Wong PC,Luettgen JM,Knabb RM,Wexler RR,Lam PY

    更新日期：2007-03-01 00:00:00

  • Double stranded DNA discrimination by di-pyrene modified gamma-cyclodextrin.

    abstract：:Neutral fluorescent active di-pyrene modified gamma-cyclodextrin (1) was synthesized in order to discriminate with single and double strand DNA (ssDNA and dsDNA, respectively) with high selectivity. The binding and selectivity of 1 for dsDNA was indicated by increase of the fluorescent intensity in an addition of dsDN...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.04.066

    authors： Takeda A,Akimoto K,Kondo Y,Hamada F

    更新日期：2010-06-01 00:00:00

  • Antifungal activity of substituted aurones.

    abstract：:Novel antifungals are in high demand as there is a growing resistance to antifungals currently in use. In particular, opportunistic fungal infections caused by Candida spp. are on the rise with infections by this genus accounting for the most severe fungal infections following chemotherapy, implantation procedures, an...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.01.012

    authors： Sutton CL,Taylor ZE,Farone MB,Handy ST

    更新日期：2017-02-15 00:00:00

  • Effective molarity in a nucleic acid-controlled reaction.

    abstract：:Positioning of reactive functional groups within a DNA duplex can enable chemical reactions that otherwise would not occur to an appreciable extent. However, few studies have quantitatively defined the extent to which the enforced proximity of reaction partners in duplex DNA can favor chemical processes. Here, we meas...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.04.022

    authors： Catalano MJ,Price NE,Gates KS

    更新日期：2016-06-01 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

  • Chemoselective enrichment as a tool to increase access to bioactive natural products: Case study borrelidin.

    abstract：:Chemoselective purification technologies have seen great success in biomolecule isolation, with a classic example being the genetically-encoded His tag utilized to enrich desired proteins from a crude lysate. We sought to translate this purification tactic into a powerful tool for the isolation of natural products and...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.07.062

    authors： Trader DJ,Carlson EE

    更新日期：2015-11-01 00:00:00

  • Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A.

    abstract：:Pyrazolopyrimidines were discovered as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. In addition to its intrinsic activity, compound 9n significantly enhances nicotinic acid binding to the receptor, thereby potentiating the functional efficacy of nicotinic acid. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.039

    authors： Shen HC,Taggart AK,Wilsie LC,Waters MG,Hammond ML,Tata JR,Colletti SL

    更新日期：2008-09-15 00:00:00

  • Discovery and structure-activity relationships of pentanedioic acid diamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type I.

    abstract：:Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.03.140

    authors： Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

    更新日期：2009-05-15 00:00:00

  • Recent advances in natural antifungal flavonoids and their derivatives.

    abstract：:The resistance of pathogenic fungi and failure of drug therapy increased dramatically. Numerous studies have reported the individual or synergistic antifungal potency of natural and synthesized flavonoids, especially against drug-resistant fungi. This brief review summarizes the structure and individual or synergistic...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2019.07.048

    authors： Jin YS

    更新日期：2019-10-01 00:00:00

  • Tra1 as a screening target for transcriptional activation domain discovery.

    abstract：:There is tremendous interest in developing activator artificial transcription factors that functionally mimic endogenous transcriptional activators for use as mechanistic probes, as components of synthetic cell circuitry, and in transcription-targeted therapies. Here, we demonstrate that a phage display selection agai...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.05.045

    authors： Majmudar CY,Labut AE,Mapp AK

    更新日期：2009-07-15 00:00:00

  • An unprecedented dual antagonist and agonist of human Transglutaminase 2.

    abstract：:Transglutaminase 2 (TG2) is a ubiquitously expressed, Ca(2+)-activated extracellular enzyme in mammals that is maintained in a catalytically dormant state by multiple mechanisms. Although its precise physiological role in the extracellular matrix remains unclear, aberrantly up-regulated TG2 activity is a hallmark of s...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.05.006

    authors： Yi MC,Palanski BA,Quintero SA,Plugis NM,Khosla C

    更新日期：2015-11-01 00:00:00