当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease.

Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease.

Abstract：

:A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Clarke MO,Chen X,Cho A,Delaney WE 4th,Doerffler E,Fardis M,Ji M,Mertzman M,Pakdaman R,Pyun HJ,Rowe T,Yang CY,Sheng XC,Kim CU

doi

10.1016/j.bmcl.2011.04.125

subject

Has Abstract

pub_date

2011-06-15 00:00:00

pages

3568-72

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00595-6

journal_volume

21

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands.

    abstract：:Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct aryl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.07.057

    authors： Ohnmacht SA,Ciancimino C,Vignaroli G,Gunaratnam M,Neidle S

    更新日期：2013-10-01 00:00:00

  • Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1.

    abstract：:Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.034

    authors： Matasi JJ,Brumfield S,Tulshian D,Czarnecki M,Greenlee W,Garlisi CG,Qiu H,Devito K,Chen SC,Sun Y,Bertorelli R,Geiss W,Le VD,Martin GS,Vellekoop SA,Haber J,Allard ML

    更新日期：2011-06-15 00:00:00

  • Affibody-displaying bio-nanocapsules effective in EGFR, typical biomarker, expressed in various cancer cells.

    abstract：:The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins deriv...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.11.038

    authors： Nishimura Y,Ezawa R,Ishii J,Ogino C,Kondo A

    更新日期：2017-01-15 00:00:00

  • Synthesis and evaluation of 2-phenyl-1,4-butanediamine-based CCR5 antagonists for the treatment of HIV-1.

    abstract：:We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.01.030

    authors： Tallant MD,Duan M,Freeman GA,Ferris RG,Edelstein MP,Kazmierski WM,Wheelan PJ

    更新日期：2011-03-01 00:00:00

  • The preparation of 2,6-disubstituted pyridinyl phosphine oxides as novel anti-cancer agents.

    abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.02.091

    authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

    更新日期：2009-04-15 00:00:00

  • Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

    abstract：:Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.01.049

    authors： Huang SC,Adhikari S,Afroze R,Brewer K,Calderwood EF,Chouitar J,England DB,Fisher C,Galvin KM,Gaulin J,Greenspan PD,Harrison SJ,Kim MS,Langston SP,Ma LT,Menon S,Mizutani H,Rezaei M,Smith MD,Zhang DM,Gould AE

    更新日期：2016-02-15 00:00:00

  • Vitamin B6s inhibit oxidative stress caused by Alzheimer's disease-related Cu(II)-β-amyloid complexes-cooperative action of phospho-moiety.

    abstract：:Cu(II) complexes of Alzheimer's disease-related β-amyloid (Aβ) peptides exhibit metal-centered oxidation chemistry. The metallo-Aβ complexes are the hallmark of the disease and have been attributed to the generation of reactive oxygen species (ROS), causing oxidative stress. In this communication, the inhibitions of t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.123

    authors： Hashim A,Wang L,Juneja K,Ye Y,Zhao Y,Ming LJ

    更新日期：2011-11-01 00:00:00

  • Novel, lipophilic derivatives of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) are powerful beta-glucosidase inhibitors.

    abstract：:Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of them, a coumarin derivative, ranks amongst the most active compounds in the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00126-3

    authors： Wrodnigg TM,Withers SG,Stütz AE

    更新日期：2001-04-23 00:00:00

  • Amides of xanthurenic acid as zinc-dependent inhibitors of Lp-PLA(2).

    abstract：:AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+)...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.045

    authors： Lin EC,Hu Y,Amantea CM,Pham LM,Cajica J,Okerberg E,Brown HE,Fraser A,Du L,Kohno Y,Ishiyama J,Kozarich JW,Shreder KR

    更新日期：2012-01-15 00:00:00

  • Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety.

    abstract：:A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.05.059

    authors： He H,Wang X,Shi L,Yin W,Yang Z,He H,Liang Y

    更新日期：2016-07-15 00:00:00

  • Design and synthesis of a novel peptidomimetic inhibitor of HIV-1 Tat-TAR interactions: squaryldiamide as a new potential bioisostere of unsubstituted guanidine.

    abstract：:By performing RNA-targeted structure-activity relationship studies, we discovered a novel peptidomimetic containing squaryldiamide as a potential bioisostere replacement for guanidine that binds transactivation responsive RNA with high affinity. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.06.077

    authors： Lee CW,Cao H,Ichiyama K,Rana TM

    更新日期：2005-10-01 00:00:00

  • Novel route to the synthesis of peptides containing 2-amino-1'-hydroxymethyl ketones and their application as cathepsin K inhibitors.

    abstract：:Cathepsin K is highly expressed in human osteoclasts, and is implicated in bone resorption. This makes it an attractive target for the treatment of osteoporosis. Peptides containing 2-amino-1'-hydroxymethyl ketones and 2-amino-1'-alkoxymethyl ketones were discovered as potent inhibitors of cathepsin K. A novel synthet...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00611-x

    authors： Mendonca RV,Venkatraman S,Palmer JT

    更新日期：2002-10-21 00:00:00

  • Synthesis of deuterium-labelled analogues of NLRP3 inflammasome inhibitor MCC950.

    abstract：:This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the hexa deuter...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.12.054

    authors： Salla M,Butler MS,Massey NL,Reid JC,Cooper MA,Robertson AAB

    更新日期：2018-02-15 00:00:00

  • Synthesis of new triazole fused imidazo[2,1-b]thiazole hybrids with emphasis on Staphylococcus aureus virulence factors.

    abstract：:A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a-u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited significant anti-biofilm activity with single and mixed biofilm d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.08.025

    authors： Shareef MA,Sirisha K,Sayeed IB,Khan I,Ganapathi T,Akbar S,Ganesh Kumar C,Kamal A,Nagendra Babu B

    更新日期：2019-10-01 00:00:00

  • Synthesis and biological evaluation of [D-lysine]8cyclosporin A analogs as potential anti-HCV agents.

    abstract：:An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclospori...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.09.036

    authors： Scribner A,Houck D,Huang Z,Mosier S,Peel M,Scorneaux B

    更新日期：2010-11-15 00:00:00

  • Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.

    abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127456

    authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

    更新日期：2020-10-01 00:00:00

  • On-resin macrocyclization of peptides via intramolecular SnAr reactions.

    abstract：:On-resin macrocyclization via an SNAr reaction is employed in the synthesis of tocinoic acid analogs. Specifically, an N-terminal nitrofluorobenzene is attacked by a nucleophilic C-terminal sidechain. The remaining nitro group can be reduced and acylated. NMR is used to compare the conformation of the new macrocyclic ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00356-x

    authors： Fotsch C,Kumaravel G,Sharma SK,Wu AD,Gounarides JS,Nirmala NR,Petter RC

    更新日期：1999-08-02 00:00:00

  • Novel triclabendazole prodrug: A highly water soluble alternative for the treatment of fasciolosis.

    abstract：:In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 sh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.12.004

    authors： Flores-Ramos M,Ibarra-Velarde F,Jung-Cook H,Hernández-Campos A,Vera-Montenegro Y,Castillo R

    更新日期：2017-02-01 00:00:00

  • Synthesis and preliminary biological evaluation of (2S,1'R,2'S)- and (2S,1'S,2'R)-2-(2'-phosphonocyclopropyl)glycines, two novel conformationally constrained l-AP4 analogues.

    abstract：:Two novel constrained l-AP4 analogues, (2S,1'R,2'S)- and (2S,1'S,2'R)-2-(2'-phosphonocyclopropyl)glycines (7) and (8), were synthesized and evaluated as mGluR ligands. Compound 7 showed to be a group III mGluRs agonist with micromolar activity. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.09.014

    authors： Amori L,Serpi M,Marinozzi M,Costantino G,Diaz MG,Hermit MB,Thomsen C,Pellicciari R

    更新日期：2006-01-01 00:00:00

  • Open-chain half-bastadins mimic the effects of cyclic bastadins on calcium homeostasis in cultured neurons.

    abstract：:Constraining the catechol aryl ether moiety of bastadins by incorporation into a macrocyle is not necessary in order to mimic the effects of these marine natural products on neuronal calcium homeostasis. Simple, acyclic analogs that embody the 'western' or 'eastern' parts of bastadins were found to evoke comparable re...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.09.080

    authors： Zieminska E,Lazarewicz JW,Couladouros EA,Moutsos VI,Pitsinos EN

    更新日期：2008-11-01 00:00:00

  • Delta agonist hydroxy bioisosteres: the discovery of 3-((1-benzylpiperidin-4-yl){4-[(diethylamino)carbonyl]phenyl}amino)benzamide with improved delta agonist activity and in vitro metabolic stability.

    abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.068

    authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

    更新日期：2009-11-01 00:00:00

  • Design and synthesis of 2-[4-[4-(m-(ethylsulfonamido)-phenyl) piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole (EF-7412) using neural networks. A selective derivative with mixed 5-HT1A/D2 antagonist properties.

    abstract：:A test series of 32 phenylpiperazines III with affinity for 5-HT1A and alpha1 receptors was subjected to QSAR analysis using artificial neural networks (ANNs), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha1 selectivity. Good models and predictive power were obtained for...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00254-1

    authors： López-Rodríguez ML,Morcillo MJ,Fernández E,Rosado ML,Orensanz L,Beneytez ME,Manzanares J,Fuentes JA,Schaper KJ

    更新日期：1999-06-21 00:00:00

  • Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2.

    abstract：:This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24h coverage in the rat arthritis efficacy model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.07.035

    authors： Tynebor RM,Chen MH,Natarajan SR,O'Neill EA,Thompson JE,Fitzgerald CE,O'Keefe SJ,Doherty JB

    更新日期：2012-09-15 00:00:00

  • An alternative to Western blot analysis using RNA aptamer-functionalized quantum dots.

    abstract：:To make full use both of optical properties of quantum dots (QDs) and of specific interactions between aptamers and their ligands of interest, we employed QD-conjugated RNA aptamer interactions with histidine tag. QDs offer revolutionary fluorescence performance due to their long-term photostability, brilliant colors,...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.04.040

    authors： Shin S,Kim IH,Kang W,Yang JK,Hah SS

    更新日期：2010-06-01 00:00:00

  • Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives.

    abstract：:A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC(50) values for inhibition of 5-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.06.012

    authors： Hansen FK,Khankischpur M,Tolaymat I,Mesaros R,Dannhardt G,Geffken D

    更新日期：2012-08-01 00:00:00

  • Syntheses and studies of quinolone-cephalosporins as potential anti-tuberculosis agents.

    abstract：:The syntheses and anti-tuberculosis activity of quinolone-cephalosporin conjugates (1 and 2) are described. Both showed broad-spectrum antibacterial activity and significant anti-TB activity. The carbamate-linked quinolone-cephem 2 showed better antimycobacterial activity, including anti-TB activity, than the direct a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.08.045

    authors： Zhao G,Miller MJ,Franzblau S,Wan B,Möllmann U

    更新日期：2006-11-01 00:00:00

  • Solution and solid phase combinatorial synthesis of peptidomimetic library containing diversified alpha-methylated amino acids.

    abstract：:A combinatorial peptidomimetic library containing diversified alpha-methylated amino acids was generated by the Ugi four component condensation (4cc) reaction from acids, amines, isocyanides and ketones in both solution and solid phase synthetic procedures. This one-pot methodology overall gave fair to good yields, wh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00279-0

    authors： Kim SW,Shin YS,Ro S

    更新日期：1998-07-07 00:00:00

  • Novel synthetic ligands for targeted PET imaging and radiotherapy of copper.

    abstract：:Novel ligands, NBEA, NBPA, NETA, NE3TA, and NE3TA-Bn, were synthesized and evaluated as potential chelators of copper radioisotopes for use in targeted positron emission tomography (PET) imaging or radiation therapy. The new ligands were radiolabeled with (64)Cu, and in vitro stability of the radiolabeled complexes wa...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.09.052

    authors： Chong HS,Mhaske S,Lin M,Bhuniya S,Song HA,Brechbiel MW,Sun X

    更新日期：2007-11-15 00:00:00

  • Exploring amino acids derivatives as potent, selective, and direct agonists of sphingosine-1-phosphate receptor subtype-1.

    abstract：:In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in v...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.11.053

    authors： Evindar G,Deng H,Bernier SG,Doyle E,Lorusso J,Morgan BA,Westlin WF

    更新日期：2013-01-15 00:00:00

  • 5-aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).

    abstract：:Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00135-5

    authors： Witherington J,Bordas V,Haigh D,Hickey DM,Ife RJ,Rawlings AD,Slingsby BP,Smith DG,Ward RW

    更新日期：2003-05-05 00:00:00