Alpha-ketoamides, alpha-ketoesters and alpha-diketones as HCV NS3 protease inhibitors.

Abstract:

:Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM.

journal_name

Bioorg Med Chem Lett

authors

Han W,Hu Z,Jiang X,Decicco CP

doi

10.1016/s0960-894x(00)00074-3

subject

Has Abstract

pub_date

2000-04-17 00:00:00

pages

711-3

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(00)00074-3

journal_volume

10

pub_type

杂志文章
  • A new class of sulfoxide surfactants derived from Tris. Synthesis and preliminary assessments of their properties.

    abstract::A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00263-7

    authors: Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

    更新日期:1998-06-16 00:00:00

  • Which aminoglycoside ring is most important for binding? A hydropathic analysis of gentamicin, paromomycin, and analogues.

    abstract::The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00615-6

    authors: Cashman DJ,Rife JP,Kellogg GE

    更新日期:2001-01-22 00:00:00

  • Recent progress in human telomere RNA structure and function.

    abstract::Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmcl.2018.06.021

    authors: Xu Y

    更新日期:2018-08-15 00:00:00

  • Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility.

    abstract::Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.12.026

    authors: Zak M,Liederer BM,Sampath D,Yuen PW,Bair KW,Baumeister T,Buckmelter AJ,Clodfelter KH,Cheng E,Crocker L,Fu B,Han B,Li G,Ho YC,Lin J,Liu X,Ly J,O'Brien T,Reynolds DJ,Skelton N,Smith CC,Tay S,Wang W,Wang Z,Xi

    更新日期:2015-02-01 00:00:00

  • Synthesis, in vitro, and in vivo antibacterial activity of nocathiacin I thiol-Michael adducts.

    abstract::The synthesis and antibacterial activity of a series of nocathiacin I derivatives (4-20) containing polar water solubilizing groups is described. Thiol-Michael adducts containing acidic polar groups have reduced antibacterial activity whereas those with basic polar groups have retained very good antibacterial activity...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.02.046

    authors: Naidu BN,Sorenson ME,Bronson JJ,Pucci MJ,Clark JM,Ueda Y

    更新日期:2005-04-15 00:00:00

  • New monoterpene glycosides from Paeonia suffruticosa Andrews and their inhibition on NO production in LPS-induced RAW 264.7 cells.

    abstract::Nine new monoterpene glycosides (1-9), together with 18 known compounds were obtained from the n-butanol soluble fraction of ethanol extract from Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectroscopic data. The inhibitory effects of these compounds (except com...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.09.034

    authors: Ding L,Zhao F,Chen L,Jiang Z,Liu Y,Li Z,Qiu F,Yao X

    更新日期:2012-12-01 00:00:00

  • Heteroarylureas with fused bicyclic diamine cores as inhibitors of fatty acid amide hydrolase.

    abstract::A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Se...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127463

    authors: Keith JM,Jones W,Pierce JM,Seierstad M,Palmer JA,Webb M,Karbarz M,Scott BP,Wilson SJ,Luo L,Wennerholm M,Chang L,Rizzolio M,Rynberg R,Chaplan S,Guy Breitenbucher J

    更新日期:2020-10-15 00:00:00

  • A discovery of novel Mycobacterium tuberculosis pantothenate synthetase inhibitors based on the molecular mechanism of actinomycin D inhibition.

    abstract::Mycobacterium tuberculosis pantothenate synthetase is a potential anti-tuberculosis target, and a high-throughput screening system was previously developed to identify its inhibitors. Using a similar system, we screened a small library of compounds and identified actinomycin D (ActD) as a weak inhibitor of pantothenat...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.05.021

    authors: Yang Y,Gao P,Liu Y,Ji X,Gan M,Guan Y,Hao X,Li Z,Xiao C

    更新日期:2011-07-01 00:00:00

  • Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers.

    abstract::The transcription factor ΔFosB accumulates in response to chronic insults such as drugs of abuse, L-3,4-dihydroxyphenylalanine (l-DOPA) or stress in specific regions of the brain, triggering long lasting neural and behavioral changes that underlie aspects of drug addiction, dyskinesia, and depression. Thus, small mole...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127300

    authors: Li Y,Liu Z,Aglyamova G,Chen J,Chen H,Bhandari M,White MA,Rudenko G,Zhou J

    更新日期:2020-08-15 00:00:00

  • Highly sensitive and selective detection of Al(III) ions in aqueous buffered solution with fluorescent peptide-based sensor.

    abstract::A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore detected selectively Al(III) among 16 metal ions in aqueous buffered solutions without any organic cosolvent. The peptide-based sensor showed a highly sensitive turn on response to aluminium ion with high binding affinity (1.84×10(4)M(-1)...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.07.073

    authors: In B,Hwang GW,Lee KH

    更新日期:2016-09-15 00:00:00

  • Synthesis and antitumor activity of s-tetrazine derivatives.

    abstract::Fifty-five compounds of s-tetrazine derivative including hexahydro-, 1,6-dihydro, 1,4-dihydro-, 1,2-dihydro- and aromatic s-tetrazine were prepared. Their antitumor activities were evaluated in vitro by MTT method for P-388 cell and SRB method for A-549 cell. The results show that there are 9 compounds which in 10(-6)...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2003.12.056

    authors: Hu WX,Rao GW,Sun YQ

    更新日期:2004-03-08 00:00:00

  • Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

    abstract::From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to b...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.01.059

    authors: Thonhofer M,Weber P,Santana AG,Fischer R,Pabst BM,Paschke E,Schalli M,Stütz AE,Tschernutter M,Windischhofer W,Withers SG

    更新日期:2016-03-01 00:00:00

  • Design and synthesis of carbamate and thiocarbamate derivatives and their inhibitory activities of NO production in LPS activated macrophages.

    abstract::Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.03.010

    authors: Jin GH,Lee HJ,Gim HJ,Ryu JH,Jeon R

    更新日期:2012-05-01 00:00:00

  • A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO).

    abstract::A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so tha...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.08.141

    authors: Liang G,Choi-Sledeski YM,Poli G,Chen X,Shum P,Minnich A,Wang Q,Tsay J,Sides K,Cairns J,Stoklosa G,Nieduzak T,Zhao Z,Wang J,Vaz RJ

    更新日期:2010-11-15 00:00:00

  • Enzymatic syntheses of 6-(4H-selenolo[3,2-b]pyrrolyl)-L-alanine, 4-(6H-selenolo[2,3-b]pyrrolyl)-L-alanine, and 6-(4H-furo[3,2-b]pyrrolyl-L-alanine.

    abstract::6-(4H-Selenolo[3,2-b]pyrrolyl)-L-alanine 1, 4-(6H-selenolo[2,3-b]pyrrolyl)-L-alanine 2, and 6-(4H-furo[3,2-b]pyrrolyl)-L-alanine 3 have been synthesized via reactions of selenolo[3,2-b]pyrrole, selenolo[2,3-b]pyrrole, and furo[3,2-b]pyrrole, respectively, with L-serine. The reactions are catalyzed by Salmonella typhim...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00067-0

    authors: Welch M,Phillips RS

    更新日期:1999-03-08 00:00:00

  • Correlation analyses on binding affinity of substituted benzenesulfonamides with carbonic anhydrase using ab initio MO calculations on their complex structures (II).

    abstract::We proposed a novel QSAR (quantitative structure-activity relationship) procedure called LERE (linear expression by representative energy terms)-QSAR involving molecular calculations such as ab initio fragment molecular orbital and generalized Born/surface area ones. We applied LERE-QSAR to two datasets for the free-e...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.11.050

    authors: Munei Y,Shimamoto K,Harada M,Yoshida T,Chuman H

    更新日期:2011-01-01 00:00:00

  • An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II.

    abstract::The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.10.045

    authors: Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

    更新日期:2011-05-01 00:00:00

  • Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors.

    abstract::Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Using active site homology and previous structure-activity relations...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.10.027

    authors: Kaller MR,Zhong W,Henley C,Magal E,Nguyen T,Powers D,Rzasa RM,Wang W,Xiong X,Norman MH

    更新日期:2009-12-01 00:00:00

  • Discovery and SAR of a novel series of Natriuretic Peptide Receptor-A (NPR-A) agonists.

    abstract::Novel thienopyrimidine compounds 2 and 3 were discovered from high-throughput screening as Natriuretic Peptide Receptor A (NPR-A) agonists. Scaffold hopping of a thienopyrimidine ring to a quinazoline ring, introduction of the basic functional group and optimization of the substituent on the 6-position of the benzene ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.09.028

    authors: Iwaki T,Nakamura Y,Tanaka T,Ogawa Y,Iwamoto O,Okamura Y,Kawase Y,Furuya M,Oyama Y,Nagayama T

    更新日期:2017-11-01 00:00:00

  • Gram-scale synthesis of pinusolide and evaluation of its antileukemic potential.

    abstract::Pinusolide (1), a known platelet-activating factor (PAF) receptor binding antagonist, was synthesized from lambertianic acid (2), a labdane-type diterpene readily accessible in multigram quantities from the Siberian pine tree. It was shown that 1 not only decreases the proliferation activity of tumor cells at relative...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.05.077

    authors: Shults EE,Velder J,Schmalz HG,Chernov SV,Rubalova TV,Gatilov YV,Henze G,Tolstikov GA,Prokop A

    更新日期:2006-08-15 00:00:00

  • Structure-activity relationships of neuropeptide Y Y1 receptor antagonists related to BIBP 3226.

    abstract::Analogues of BIBP 3226, (R)-N(alpha)-diphenylacetyl-N-(4-hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity. Combination with a N(G)...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00292-4

    authors: Aiglstorfer I,Hendrich I,Moser C,Bernhardt G,Dove S,Buschauer A

    更新日期:2000-07-17 00:00:00

  • Carbohydrate-modulated DNA photocleavage: design, synthesis, and evaluation of novel glycosyl anthraquinones.

    abstract::Novel and artificial anthraquinone-carbohydrate hybrids were designed and synthesized, and found to effectively cleave DNA under irradiation with a long wavelength UV light and also exhibit cytotoxicity against HeLa S3 cells. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00410-8

    authors: Toshima K,Maeda Y,Ouchi H,Asai A,Matsumura S

    更新日期:2000-10-02 00:00:00

  • Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents.

    abstract::Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.07.078

    authors: Shah K,Patel D,Jadav P,Sheikh M,Sairam KV,Joharapurkar A,Jain MR,Bahekar R

    更新日期:2012-09-15 00:00:00

  • Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

    abstract::Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target fo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.09.008

    authors: Sparks SM,Spearing PK,Diaz CJ,Cowan DJ,Jayawickreme C,Chen G,Rimele TJ,Generaux C,Harston LT,Roller SG

    更新日期:2017-10-15 00:00:00

  • InCl3 mediated one-pot multicomponent synthesis, anti-microbial, antioxidant and anticancer evaluation of 3-pyranyl indole derivatives.

    abstract::A simple and convenient method for the one-pot three-component synthesis of 3-pyranyl indoles has been accomplished by tandem Knoevenagel-Michael reaction of 3-cyanoacetyl indole, various aromatic aldehydes and malononitrile catalyzed by InCl(3) in ethanol under reflux conditions. The newly synthesized 3-pyranyl indol...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.07.039

    authors: Lakshmi NV,Thirumurugan P,Noorulla KM,Perumal PT

    更新日期:2010-09-01 00:00:00

  • 2'-Deoxy-2'(S)-ethinyl oligonucleotides: a modification which selectively stabilizes oligoadenylate pairing to DNA complements.

    abstract::Oligonucleotides consisting of 2'-deoxy-2'(S)-ethinyl-thymidine,-uridine, and -adenosine have been prepared. Whereas the modified pyrimidine oligonucleotides uniformly lead to weaker pairing affinity with DNA and RNA complements, the corresponding adenine oligonucleotides show enhanced thermal stability in duplexes wi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00060-2

    authors: Buff R,Hunziker J

    更新日期:1998-03-03 00:00:00

  • Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors.

    abstract::The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00602-8

    authors: Cowart M,Lee CH,Gfesser GA,Bayburt EK,Bhagwat SS,Stewart AO,Yu H,Kohlhaas KL,McGaraughty S,Wismer CT,Mikusa J,Zhu C,Alexander KM,Jarvis MF,Kowaluk EA

    更新日期:2001-01-08 00:00:00

  • Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells.

    abstract::P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127355

    authors: Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

    更新日期:2020-09-01 00:00:00

  • Identification of peptidomimetic HTLV-I protease inhibitors containing hydroxymethylcarbonyl (HMC) isostere as the transition-state mimic.

    abstract::Towards the development of chemotherapy for the infection by human T-cell leukemia virus type I (HTLV-I), we have established evaluation systems for HTLV-I protease (PR) inhibitors using both recombinant and chemically synthesized HTLV-I PRs. Newly synthesized substrate-based inhibitors containing hydroxymethylcarbony...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.09.034

    authors: Maegawa H,Kimura T,Arii Y,Matsui Y,Kasai S,Hayashi Y,Kiso Y

    更新日期:2004-12-06 00:00:00

  • New adjuvants to enhance anticoagulant activity of warfarin.

    abstract::New adjuvants of warfarin anticoagulant activity have been developed. These compounds, which are 1,4-methano-1,2,3,4-tetrahydroanthracene-9,10-diol derivatives, act synergistically with warfarin to potentiate its anticoagulant effect. None of the compounds tested is an effective oral anticoagulant in the absence of wa...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.01.123

    authors: Stromich JJ,Weber AK,Mirzaei YR,Caldwell MD,Lewis DE

    更新日期:2010-03-15 00:00:00