Absolute configurations of tubulin inhibitors taltobulin (HTI-286) and HTI-042 characterized by X-ray diffraction analysis and NMR studies.

abstract：:Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qiang X,Li Y,Yang X,Luo L,Xu R,Zheng Y,Cao Z,Tan Z,Deng Y

更新日期：2017-02-15 00:00:00

abstract：:Sialidases are key virulence factors that remove sialic acid from host cell surface glycans, thus unmasking receptors to facilitate bacterial adherence and colonization. In this study, we report the isolation and characterization of novel inhibitors of the Streptococcus pneumoniae sialidases NanA, NanB, and NanC from ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park JY,Hwan Lim S,Ram Kim B,Jae Jeong H,Kwon HJ,Song GY,Bae Ryu Y,Song Lee W

更新日期：2017-07-15 00:00:00

abstract：:A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [(35)S]GTPgammaS assay are reported. The most potent and selective delta-opioid agoni...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trabanco AA,Pullan S,Alonso JM,Alvarez RM,Andrés JI,Boeckx I,Fernández J,Gómez A,Iturrino L,Janssens FE,Leenaerts JE,De Lucas AI,Matesanz E,Meert T,Steckler T

更新日期：2006-01-01 00:00:00

abstract：:New indole-porphyrin hybrid molecules were isolated from Escherichia coli harboring metagenomic DNA from the Japanese marine sponge Discodermia calyx. The indole was appended to the reactive vinyl substituent of the harderoporphyrin chromophore, encoded by the insert DNA. Thus, the chimeric pathway between the heterol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang XL,Wakimoto T,Takeshige Y,He R,Egami Y,Awakawa T,Abe I

更新日期：2013-07-01 00:00:00

abstract：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

更新日期：2015-12-15 00:00:00

abstract：:A series of benzimidazole-based inhibitors of respiratory syncytial virus (RSV) fusion were optimized for antiviral potency, membrane permeability and metabolic stability in human liver microsomes. 1-Cyclopropyl-1,3-dihydro-3-[[1-(4-hydroxybutyl)-1H-benzimidazol-2-yl]methyl]-2H-imidazo[4,5-c]pyridin-2-one (6m, BMS-433...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu KL,Sin N,Civiello RL,Wang XA,Combrink KD,Gulgeze HB,Venables BL,Wright JJ,Dalterio RA,Zadjura L,Marino A,Dando S,D'Arienzo C,Kadow KF,Cianci CW,Li Z,Clarke J,Genovesi EV,Medina I,Lamb L,Colonno RJ,Yang Z,Kr

更新日期：2007-02-15 00:00:00

abstract：:A series of 1-(quinoliloxypropyl)-4-aryl-piperazines has been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypic behaviour in mice. The 8-hydroxyquinoline ether derivative 14 has emerged as an important lead compound showing a potenti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bali A,Malhotra S,Dhir H,Kumar A,Sharma A

更新日期：2009-06-01 00:00:00

abstract：:A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have...

journal_title：Bioorganic & medicinal chemistry letters

authors： Youssef D,Nichols CE,Cameron TS,Balzarini J,De Clercq E,Jha A

更新日期：2007-10-15 00:00:00

abstract：:The in vitro antimycobacterial activity of cobalt(II) and copper(II) complexes of some fluorinated isonicotinoylhydrazones was evaluated in a TB-infected macrophage model; all metalcomplexes exhibited excellent activity against Mycobacterium tuberculosis Erdman growing within macrophages, at concentrations much lower ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maccari R,Ottanà R,Bottari B,Rotondo E,Vigorita MG

更新日期：2004-12-06 00:00:00

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

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

abstract：:A novel dendritic molecule with nine chlorambucil (CBL) residues on the surface and a maleimide moiety at the core terminus was synthesized using a convergent synthetic methodology. This molecule is ready for attachment to single-chain Fv antibodies (scFvs) to form antibody-multidrug immunoconjugates in an effort to s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun C,Wirsching P,Janda KD

更新日期：2002-08-19 00:00:00

abstract：:The use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. Lupeol was anchored to a solid support (Rink amide/Sieber Amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. The resulting polymer linked 3beta-O (resin-al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Srinivasan T,Srivastava GK,Pathak A,Batra S,Raj K,Singh K,Puri SK,Kundu B

更新日期：2002-10-21 00:00:00

abstract：:We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takeda Y,Yoshino T,Uoto K,Chiba J,Ishiyama T,Iwahana M,Jimbo T,Tanaka N,Terasawa H,Soga T

更新日期：2003-01-20 00:00:00

abstract：:Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Robinson RP,Bartlett JA,Bertinato P,Bessire AJ,Cosgrove J,Foley PM,Manion TB,Minich ML,Ramos B,Reese MR,Schmahai TJ,Swick AG,Tess DA,Vaz A,Wolford A

更新日期：2011-07-15 00:00:00

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

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

更新日期：2020-02-01 00:00:00

abstract：:Structure-guided design led to the discovery of novel chemical scaffolds for B-Raf inhibitors. Both type I and type II kinase inhibitors have been explored and lead compounds with good potency and excellent selectivity have been identified. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang X,Salaski EJ,Berger DM,Powell D,Hu Y,Wojciechowicz D,Collins K,Frommer E

更新日期：2011-12-01 00:00:00

abstract：:N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1-alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino derivatives displayed comparable potency to carbon analogs. Analogs with aliphatic substitu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pratt JK,Donner P,McDaniel KF,Maring CJ,Kati WM,Mo H,Middleton T,Liu Y,Ng T,Xie Q,Zhang R,Montgomery D,Molla A,Kempf DJ,Kohlbrenner W

更新日期：2005-03-15 00:00:00

abstract：:B-Raf kinase plays a critical role in the Raf-MEK-ERK signaling pathway and inhibitors of B-Raf could be used in the treatment of melanomas, colorectal cancer, and other Ras related human cancers. We have identified novel small molecule pyrazolo[1,5-a]pyrimidine derivatives as B-Raf kinase inhibitors. Structure-activi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gopalsamy A,Ciszewski G,Hu Y,Lee F,Feldberg L,Frommer E,Kim S,Collins K,Wojciechowicz D,Mallon R

更新日期：2009-05-15 00:00:00

abstract：:The Naturally occurring novel cyclohexanonyl bromophenol 2(R)-2-(2,3,6-tribromo-4,5-dihydroxybenzyl)cyclohexanone (4) was synthesized as a racemic compound. Cyclohexylphenyl methane derivatives (10-17) with Br, OMe, CO, and OH were also obtained. Inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I...

journal_title：Bioorganic & medicinal chemistry letters

authors： Balaydın HT,Sentürk M,Menzek A

更新日期：2012-02-01 00:00:00

abstract：:The enantioselective activation of nitroalkanes was attempted on the basis of the complexation between chiral guanidinium and nitronate through two hydrogen bonds. The proposed enantioselective activation was applied to the diastereo- and enantioselective Henry (nitroaldol) reaction of nitroalkanes with aldehydes usin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ube H,Terada M

更新日期：2009-07-15 00:00:00

abstract：:A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi J,Zhu J,Liu X,Ding L,Zheng C,Han G,Lv J,Zhou Y

更新日期：2011-10-01 00:00:00

abstract：:From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibito...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pick A,Müller H,Wiese M

更新日期：2010-01-01 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：:Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Breslin MJ,Duggan ME,Halczenko W,Fernandez-Metzler C,Hunt CA,Leu CT,Merkle KM,Naylor-Olsen AM,Prueksaritanont T,Stump G,Wallace A,Rodan SB,Hutchinson JH

更新日期：2003-05-19 00:00:00

abstract：:Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang W,Devasthale P,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Li YX,Zahler R,Kirby MS,Hamann LG

更新日期：2011-11-15 00:00:00

abstract：:Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were iden...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah U,Boyle CD,Chackalamannil S,Baker H,Kowalski T,Lee J,Terracina G,Zhang L

更新日期：2010-03-01 00:00:00

abstract：:In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Girault S,Davioud-Charvet E,Salmon L,Berecibar A,Debreu MA,Sergheraert C

更新日期：1998-05-19 00:00:00

abstract：:We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu Q,Liu W,Ding J,Cai J,Duan W

更新日期：2002-05-20 00:00:00

abstract：:We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zou Y,Albohy A,Sandbhor M,Cairo CW

更新日期：2010-12-15 00:00:00

abstract：:A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Regan CF,Guo Z,Chen Y,Huang CQ,Chen M,Jiang W,Rueter JK,Coon T,Chen C,Saunders J,Brown MS,Betz SF,Struthers RS,Yang C,Wen J,Madan A,Zhu YF

更新日期：2008-08-15 00:00:00