Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties.


:We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series.


Bioorg Med Chem Lett


Li X,Zhang S,Zhang YK,Liu Y,Ding CZ,Zhou Y,Plattner JJ,Baker SJ,Bu W,Liu L,Kazmierski WM,Duan M,Grimes RM,Wright LL,Smith GK,Jarvest RL,Ji JJ,Cooper JP,Tallant MD,Crosby RM,Creech K,Ni ZJ,Zou W,Wright J




Has Abstract


2011-04-01 00:00:00














  • Cathepsin B inhibitory activities of phthalates isolated from a marine Pseudomonas strain.

    abstract::Two cathepsin B inhibitors were isolated from the culture supernatant of a marine Pseudomonas sp. PB01 (GenBank Accession No. EU126129). Their structures were elucidated by spectroscopic analyses as dibutyl phthalate and di-(2-ethylhexyl) phthalate. Both dibutyl phthalate and di-(2-ethylhexyl) phthalate showed dose-de...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hoang VL,Li Y,Kim SK

    更新日期:2008-03-15 00:00:00

  • Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.

    abstract::The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhao DG,Ma YY,Peng W,Zhou AY,Zhang Y,Ding L,Du Z,Zhang K

    更新日期:2016-01-01 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


    authors: Ramalingam P,Ganapaty S,Rao ChB

    更新日期:2010-01-01 00:00:00

  • Peptide chemistry applied to a new family of phenothiazine-containing inhibitors of human farnesyltransferase.

    abstract::Novel phenothiazine derivatives bearing an amino acid residue were synthesized via peptide chemistry, and evaluated for their inhibitory potential on human farnesyltransferase. The phenothiazine unit proved to be an important bulky unit in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a tyros...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dumitriu GM,Ghinet A,Bîcu E,Rigo B,Dubois J,Farce A,Belei D

    更新日期:2014-07-15 00:00:00

  • Synthesis and antibacterial activity of 3-benzylamide derivatives as FtsZ inhibitors.

    abstract::The emergence and spread of multidrug-resistant strains of the human pathological bacteria are generating a threat to public health worldwide. In the current study, a series of PC190723 derivatives was synthesized and investigated for their antimicrobial activity. The compounds exhibited good activity against several ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hu Z,Zhang S,Zhou W,Ma X,Xiang G

    更新日期:2017-04-15 00:00:00

  • New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation.

    abstract::A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Singh A,Sharma S,Arora S,Attri S,Kaur P,Kaur Gulati H,Bhagat K,Kumar N,Singh H,Vir Singh J,Mohinder Singh Bedi P

    更新日期:2020-10-15 00:00:00

  • Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

    abstract::A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more pot...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ding L,Tang F,Huang W,Jin Q,Shen H,Wei P

    更新日期:2013-10-15 00:00:00

  • Anti-herpes simplex virus efficacies of 2-aminobenzamide derivatives as novel HSP90 inhibitors.

    abstract::After the widespread use of the acyclic purine nucleoside analogues for therapy of herpes simplex virus (HSV) infection since the 1980s, new antiviral strategies are urgently needed to counter the emergence of drug-resistant clinical isolates. In this report, we define the anti-HSV efficacies of three optimized 2-amin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xiang YF,Qian CW,Xing GW,Hao J,Xia M,Wang YF

    更新日期:2012-07-15 00:00:00

  • Triaryl (Z)-olefins suitable for radiolabeling with iodine-124 or fluorine-18 radionuclides for positron emission tomography imaging of estrogen positive breast tumors.

    abstract::A group of (Z)-1,2-diphenyl-1-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]but-1-enes were synthesized using methodologies that will allow incorporation of a [(124)I]iodine substituent at the para-position of either the C-1 phenyl ring or the C-2 phenyl ring, or a [(18)F]OCH(2)CH(2)F substituent at the para-position of...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Abdellatif KR,Velázquez CA,Huang Z,Chowdhury MA,Knaus EE

    更新日期:2011-02-15 00:00:00

  • Discovery of potent and selective histamine H3 receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold.

    abstract::A novel series of potent histamine H(3) receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several compounds display high selectivity over other histamine receptor subtypes and have favorable physicochemical properties, low potential for CYP450 enzyme inhibit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Richter HG,Freichel C,Huwyler J,Nakagawa T,Nettekoven M,Plancher JM,Raab S,Roche O,Schuler F,Taylor S,Ullmer C,Wiegand R

    更新日期:2010-10-01 00:00:00

  • Discovery of diarylpyridine derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

    abstract::Two series (4 and 5) of diarylpyridine derivatives were designed, synthesized, and evaluated for anti-HIV-1 activity. The most promising compound, 5e, inhibited HIV-1 IIIB, NL4-3, and RTMDR1 with low nanomolar EC50 values and selectivity indexes of >10,000. The results of this study indicate that diarylpyridine can be...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tian X,Qin B,Lu H,Lai W,Jiang S,Lee KH,Chen CH,Xie L

    更新日期:2009-09-15 00:00:00

  • An atom economic synthesis and antitubercular evaluation of novel spiro-cyclohexanones.

    abstract::The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quant...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ranjith Kumar R,Perumal S,Manju SC,Bhatt P,Yogeeswari P,Sriram D

    更新日期:2009-07-01 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


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

    更新日期:2004-08-16 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


    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

  • Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands.

    abstract::1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I(2) imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I(2) imidazoline receptors (K(i)=6.2 nM) and with exceptional (> or =1000-fold) selectivity relativ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chang-Fong J,Tyacke RJ,Lau A,Westaway J,Hudson AL,Glennon RA

    更新日期:2004-02-23 00:00:00

  • Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus and Culex quinquefasciatus.

    abstract::Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Cule...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bandyopadhyay P,Sathe M,Tikar SN,Yadav R,Sharma P,Kumar A,Kaushik MP

    更新日期:2014-07-01 00:00:00

  • Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis.

    abstract::During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have s...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Di Santo R,Costi R,Artico M,Massa S,Lampis G,Deidda D,Pompei R

    更新日期:1998-10-20 00:00:00

  • In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

    abstract::A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (3...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ramírez-Cisneros MÁ,Rios MY,Aguilar-Guadarrama AB,Rao PP,Aburto-Amar R,Rodríguez-López V

    更新日期:2015-10-15 00:00:00

  • Cytotoxicity and DNA binding property of the dimers of triphenylethylene-coumarin hybrid with one amino side chain.

    abstract::Novel dimers of triphenylethylene-coumarin hybrid containing one amino side chain were designed and synthesized by the condensation of four dicarboxylic acids with the amino monomeric hybrids catalyzed by HATU and DIPEA at room temperature. The adding order of the reactants had a significant effect on the condensation...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tan G,Yao Y,Gu Y,Li S,Lv M,Wang K,Chen H,Li X

    更新日期:2014-07-01 00:00:00

  • Design and synthesis of bridged piperidine and piperazine isosteres.

    abstract::We have developed versatile methods toward the synthesis of a variety of piperidine/piperazine bridged isosteres of pridopidine. The compounds were assessed against the D2 receptor in agonist and antagonist modes and against the D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Maertens G,Saavedra OM,Vece V,Reyes MAV,Hocine S,Öney E,Goument B,Mirguet O,Le Tiran A,Gloanec P,Hanessian S

    更新日期:2018-08-15 00:00:00

  • 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_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Han W,Hu Z,Jiang X,Decicco CP

    更新日期:2000-04-17 00:00:00

  • Synthesis and biological evaluation of piperamide analogues as HDAC inhibitors.

    abstract::Two natural piperamides (piperlonguminine and refrofractamide A) and their derivatives were synthesized and evaluated for inhibitory activity against histone deacetylases, as well as the HCT-116 human colon cancer cell line. The preliminary structure activity relationship was discussed. Compounds featuring a hydroxami...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Luo Y,Liu HM,Su MB,Sheng L,Zhou YB,Li J,Lu W

    更新日期:2011-08-15 00:00:00

  • New class of 8-aryl-7-deazaguanine cell permeable fluorescent probes.

    abstract::A one step synthesis of fluorescent 8-aryl-(7-deazaguanines) has been accomplished. Probes exhibit blue to green high quantum yield fluorescence in a variety of organic and aqueous solutions, high extinction coefficients, and large Stokes shifts often above 100 nm. The probes are highly cell permeable, and exhibit sta...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dhimitruka I,Eubank TD,Gross AC,Khramtsov VV

    更新日期:2015-10-15 00:00:00

  • Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism.

    abstract::Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-block...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yadav MR,Naik PP,Gandhi HP,Chauhan BS,Giridhar R

    更新日期:2013-07-01 00:00:00

  • Antiproliferative and tumor inhibitory studies of 2,3 disubstituted 4-thiazolidinone derivatives.

    abstract::4-Thiazolidinone derivatives were synthesized using T3P®-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phen...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sharath Kumar KS,Hanumappa A,Vetrivel M,Hegde M,Girish YR,Byregowda TR,Rao S,Raghavan SC,Rangappa KS

    更新日期:2015-09-01 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


    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

  • Activation of antibacterial prodrugs by peptide deformylase.

    abstract::5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the defo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wei Y,Pei D

    更新日期:2000-05-15 00:00:00

  • Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties.

    abstract::A new series of Proteolysis Targeting Chimeras (PROTACs) targeting Bruton's Tyrosine Kinase (BTK) was synthesized, with the goal of improving the pharmacokinetic properties of our previously reported PROTAC, MT802. We recently described the ability of MT802 to induce degradation of both wild-type and C481S mutant BTK ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Jaime-Figueroa S,Buhimschi AD,Toure M,Hines J,Crews CM

    更新日期:2020-02-01 00:00:00

  • Synthesis and in vitro evaluation of human FP-receptor selective prostaglandin analogues.

    abstract::The in vitro evaluation of a series of saturated prostaglandins revealed that compounds with omega chain aromatic rings retain nanomolar potency for the human prostaglandin F receptor (hFP receptor), exemplified by compound 8. In contrast, the double bonds are required for activity in the series with an acyclic omega ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: deLong MA,Amburgey J,Taylor C,Wos JA,Soper DL,Wang Y,Hicks R

    更新日期:2000-07-17 00:00:00

  • Trityl radicals in perfluorocarbon emulsions as stable, sensitive, and biocompatible oximetry probes.

    abstract::EPR oximetry with the use of trityl radicals can enable sensitive O2 measurement in biological cells and tissues. However, in vitro cellular and in vivo biological applications are limited by rapid trityl probe degradation or biological clearance and the need to enhance probe O2 sensitivity. We synthesized novel perfl...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dhimitruka I,Alzarie YA,Hemann C,Samouilov A,Zweier JL

    更新日期:2016-12-01 00:00:00