Inhibitors of HCV NS5B polymerase. Part 2: Evaluation of the northern region of (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid.

abstract：:Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saxena J,Meloni D,Huang MT,Heck DE,Laskin JD,Heindel ND,Young SC

更新日期：2015-12-01 00:00:00

abstract：:Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites. In order to reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, we developed a simple cell viability assay by combining a bioactivation system (huma...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rana P,Will Y,Nadanaciva S,Jones LH

更新日期：2016-08-15 00:00:00

abstract：:We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee S,Kwon OS,Lee CS,Won M,Ban HS,Ra CS

更新日期：2017-07-01 00:00:00

abstract：:Bisubstrate analog inhibitors in which a nicotinamide mimic is attached to a series of structurally diversified guanidines (arginine mimics) were synthesized and evaluated for inhibition of cholera toxin. The mechanism-based bisubstrate inhibitors were up to 1400-fold more potent than the natural substrate NAD+ and 40...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang G

更新日期：2008-07-01 00:00:00

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

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

abstract：:The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

更新日期：2010-12-15 00:00:00

abstract：:New inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered using an N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamide scaffold. The series was found to be potent in a porcine TACE (pTACE) assay with IC(50)s typically below 5 nM. For most compounds, selectivity for pTACE relative to MMP-1,-2, and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Lu Z,Xue CB,He X,Seng JL,Roderick JJ,Wasserman ZR,Liu RQ,Covington MB,Magolda RL,Newton RC,Trzaskos JM,Decicco CP

更新日期：2003-06-16 00:00:00

abstract：:The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7alpha-allyltestosterone with 75% yield. The synthesis led to separable i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bastien D,Leblanc V,Asselin E,Bérubé G

更新日期：2010-04-01 00:00:00

abstract：:A series of isoquinuclidine benzamides as glycine uptake inhibitors for the treatment of schizophrenia are described. Potency, lipophilicity, and intrinsic human microsomal clearance were parameters for optimization. Potency correlated with the nature of the ortho substituents of the benzamide ring, and reductions in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Varnes JG,Xiong H,Forst JM,Holmquist CR,Ernst GE,Frietze W,Dembofsky B,Andisik DW,Palmer WE,Hinkley L,Steelman GB,Wilkins DE,Tian G,Jonak G,Potts WM,Wang X,Brugel TA,Alhambra C,Wood MW,Veale CA,Albert JS

更新日期：2018-04-01 00:00:00

abstract：:A multivalent approach focused on amine-based secondary binding groups was applied to the discovery of long-acting inhaled β2-agonists. Addition of amine moieties to the neutral secondary binding group of an existing β2-agonist series was found to provide improved in vivo efficacy, but also led to the formation of bio...

journal_title：Bioorganic & medicinal chemistry letters

authors： McKinnell RM,Klein U,Linsell MS,Moran EJ,Nodwell MB,Pfeiffer JW,Thomas GR,Yu C,Jacobsen JR

更新日期：2014-07-01 00:00:00

abstract：:Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arai Y,Inuki S,Fujimoto Y

更新日期：2018-05-15 00:00:00

abstract：:Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione wa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park MH,Kim IS,Kim SA,Na CS,Hong CY,Dong MS,Yoo HH

更新日期：2014-04-01 00:00:00

abstract：:We disclose a new compound class of potent and selective alpha-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are pres...

journal_title：Bioorganic & medicinal chemistry letters

authors： DiPardo RM,Patane MA,Newton RC,Price R,Broten TP,Chang RS,Ransom RW,Di Salvo J,Freidinger RM,Bock MG

更新日期：2001-07-23 00:00:00

abstract：:Four stereoisomeric hybrids of the polyketide natural products callystatin A and leptomycin B have been prepared by parallel synthetic routes involving chiral allenylstannane methodology. Like their natural counterparts, these hybrids exhibit nanomolar levels of cytotoxicity toward HCT-116 human colon cancer cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marshall JA,Mikowski AM,Bourbeau MP,Schaaf GM,Valeriote F

更新日期：2006-01-15 00:00:00

abstract：:Novel fused 1H-benzo[f]chromen-indole derivatives were synthesized regioselectivly in good to high yields by triethyl amine catalyzed condensation of 3-cyanoacetylindoles, β-naphthol and aryl aldehydes in methanol under ultrasounic irradiations and conventional conditions. The easy work-up of the products, rapidity, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hossein nia R,Mamaghani M,Tabatabaeian K,Shirini F,Rassa M

更新日期：2012-09-15 00:00:00

abstract：:Through a systematic modification of the novel angiogenesis inhibitor 4-senecioyloxymethyl-6,7-dimethoxycoumarin (1) we found that a 6,7-dimethoxy moiety is important for bioactivity of 1. Replacement of the lactone functionality in coumarin 1 by an amide decreased its activity. By substitution of the senecioyl chain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nam NH,Kim Y,You YJ,Hong DH,Kim HM,Ahn BZ

更新日期：2002-09-02 00:00:00

abstract：:The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SJ,Buschmann H,Bolm C

更新日期：2011-08-15 00:00:00

abstract：:We report here the development of a novel fluorescein-based probe which shows selective fluorescence enhancement on binding to a hexahistidine-tagged protein. No fluorescence change was observed with untagged protein. This probe is excitable with visible light and is considered to be suitable for use in biological app...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamoto M,Umezawa N,Kato N,Higuchi T

更新日期：2009-04-15 00:00:00

abstract：:Inositols play an important role in membrane lipid metabolism and mitogenic signaling of most cancer cells. There is paucity of data on the distribution of radiolabelled inositols. Based on work previously carried out on 1-deoxy-1-[(18)F]fluoro-scyllo-inositol ([(18)F]2), we began a program of work to label myo-inosit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carroll L,Perumal M,Vasdev N,Robins E,Aboagye EO

更新日期：2012-10-01 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pérez-Cruz F,Serra S,Delogu G,Lapier M,Maya JD,Olea-Azar C,Santana L,Uriarte E

更新日期：2012-09-01 00:00:00

abstract：:Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identificati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cole DC,Stock JR,Kreft AF,Antane M,Aschmies SH,Atchison KP,Casebier DS,Comery TA,Diamantidis G,Ellingboe JW,Harrison BL,Hu Y,Jin M,Kubrak DM,Lu P,Mann CW,Martone RL,Moore WJ,Oganesian A,Riddell DR,Sonnenberg-Reine

更新日期：2009-02-01 00:00:00

abstract：:In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with <10 nM potency. In addition, th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao D,Dai X,Liu H,He S,Shi ZC,Ludmerer SW,Li F,Nargund R,Palani A

更新日期：2020-04-01 00:00:00

abstract：:Cyano pyrimidine acetylene and cyano pyrimidine t-amine, which belong to a new chemical class, were prepared and tested for inhibitory activities against cathepsin K and the highly homologous cathepsins L and S. The use of novel chemotypes in the development of cathepsin K inhibitors has been demonstrated by derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Teno N,Irie O,Miyake T,Gohda K,Horiuchi M,Tada S,Nonomura K,Kometani M,Iwasaki G,Betschart C

更新日期：2008-04-15 00:00:00

abstract：:We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2-((3αS,7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H,5H,6H,7H,7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11, followed by Wittig-Horner coupl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen B,Kawai M,Wu-Wong JR

更新日期：2013-11-01 00:00:00

abstract：:A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, resp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Palmer WS,Alam M,Arzeno HB,Chang KC,Dunn JP,Goldstein DM,Gong L,Goyal B,Hermann JC,Hogg JH,Hsieh G,Jahangir A,Janson C,Jin S,Ursula Kammlott R,Kuglstatter A,Lukacs C,Michoud C,Niu L,Reuter DC,Shao A,Silva T,Tr

更新日期：2013-03-01 00:00:00

abstract：:Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Siedlecki J,Hill J,Parr I,Yu X,Morytko M,Zhang Y,Silverman J,Controneo N,Laganas V,Li T,Li J,Keith D,Shimer G,Finn J

更新日期：2003-12-01 00:00:00

abstract：:A number of prodrugs of HCV-active purine nucleoside analogues 2'-C-methyl 4-aza-9-deaza adenosine 1, 2'-C-methyl 4-aza-7,9-dideaza adenosine 2, 2'-C-methyl 4-aza-9-deaza guanosine 3 and 2'-C-methyl 4-aza-7,9-dideaza guanosine 4 were prepared and evaluated to improve potency, selectivity and liver targeting. Phosphora...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tyndall EM,Draffan AG,Frey B,Pool B,Halim R,Jahangiri S,Bond S,Wirth V,Luttick A,Tilmanis D,Thomas J,Porter K,Tucker SP

更新日期：2015-02-15 00:00:00

abstract：:We have recently reported that the elaboration of the N-substituent in the δ opioid receptor (DOR) antagonist naltrindole (NTI) enabled the regulation of the DOR activities from full inverse agonists to weak partial agonists. The investigations of amide-type NTI derivatives revealed that N-phenylacetyl and N-dihydroci...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii H,Uchida Y,Shibasaki M,Nishida M,Yoshioka T,Kobayashi R,Honjo A,Itoh K,Yamada D,Hirayama S,Saitoh A

更新日期：2020-06-15 00:00:00

abstract：:Pradimicins are a group of antiviral and antifungal natural products from Actinomadura hibisca. Two putative O-methyltransferase genes, pdmF and pdmT, are present in the pradimicin biosynthetic gene cluster. However, there is only one methoxy group (11-OCH3) in pradimicins. Through heterologous expression and in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu F,Napan K,Zhang S,Gladwin T,Takemoto J,Zhan J

更新日期：2017-08-01 00:00:00