Isotope edited NMR studies of glycosidases: design and synthesis of a novel glycosidase inhibitor.

abstract：:Experimental evidences have confirmed that matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions and recent advances in medicinal chemistry approach to the design of MMP inhibitors with desired structural and functional properties. Among MMPs, MMP-9 has demonstrated to pla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mendis E,Kim MM,Rajapakse N,Kim SK

更新日期：2006-06-15 00:00:00

abstract：:Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [(18)F]FB-GC was obtained w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang W,Mou T,Guo W,Jing H,Peng C,Zhang X,Ma Y,Liu B

更新日期：2010-08-15 00:00:00

abstract：:In the course of ongoing research on protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from Antarctic lichens, four new diterpene furanoids, hueafuranoids A-D (1-4) have been isolated from the MeOH extract of Antarctic lichen Huea sp. by various chromatographic methods. The structures of these compounds wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cui Y,Yim JH,Lee DS,Kim YC,Oh H

更新日期：2012-12-15 00:00:00

abstract：:Four N-Fmoc protected polyoxyethylene-based amino acid type linkers were designed and synthesized for peptide derivatization in solid phase. Three of them were obtained in a crystalline form. The crystallized linkers can be stored at 4 degrees C for 2 years without significant decomposition. Protocols for biotinylatio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song A,Wang X,Zhang J,Marík J,Lebrilla CB,Lam KS

更新日期：2004-01-05 00:00:00

abstract：:Amino-1,2,5-trideoxy-2,5-imino-D-mannitol was fluorescently tagged by reaction with dansyl chloride at N-1 or by attachment of a dansyl amide bearing spacer to this centre. Compounds obtained are highly potent inhibitors of beta-glucosidase exhibiting Ki values in the single figure nanomolar range. The 1-N-dansyl subs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hermetter A,Scholze H,Stütz AE,Withers SG,Wrodnigg TM

更新日期：2001-05-21 00:00:00

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

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

更新日期：2000-10-02 00:00:00

abstract：:3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hale JJ,Doherty G,Toth L,Li Z,Mills SG,Hajdu R,Ann Keohane C,Rosenbach M,Milligan J,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala S

更新日期：2004-07-05 00:00:00

abstract：:Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tend...

journal_title：Bioorganic & medicinal chemistry letters

authors： Felip-León C,Martínez-Arroyo O,Díaz-Oltra S,Miravet JF,Apostolova N,Galindo F

更新日期：2018-03-01 00:00:00

abstract：:A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

更新日期：2016-04-01 00:00:00

abstract：:3-O-tert-Butyldimethylsilyl-17 alpha-(6-mesyloxyhexynyl)estradiol was converted to the azide in 60-70% yield with NaN3/DMPU, then reduced to the corresponding amine (> 95% yield). Acylation with the N-hydroxysuccinimide esters of biotin, 5-carboxyfluorescein and 10-(3-sulfopropyl)-N-tosyl-N-(3- carboxypropyl)acridiniu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adamczyk M,Chen YY,Moore JA,Mattingly PG

更新日期：1998-06-02 00:00:00

abstract：:Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was fou...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wen W,Young SE,Duvernay MT,Schulte ML,Nance KD,Melancon BJ,Engers J,Locuson CW 2nd,Wood MR,Daniels JS,Wu W,Lindsley CW,Hamm HE,Stauffer SR

更新日期：2014-10-01 00:00:00

abstract：:The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Linder MR,Heckeroth AR,Najdrowski M,Daugschies A,Schollmeyer D,Miculka C

更新日期：2007-08-01 00:00:00

abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

更新日期：2015-08-15 00:00:00

abstract：:The synthesis and SAR of a series of novel pyrazolo-quinazolines as potent and selective MPS1 inhibitors are reported. We describe the optimization of the initial hit, identified by screening the internal library collection, into an orally available, potent and selective MPS1 inhibitor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldarelli M,Angiolini M,Disingrini T,Donati D,Guanci M,Nuvoloni S,Posteri H,Quartieri F,Silvagni M,Colombo R

更新日期：2011-08-01 00:00:00

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

authors： Ramalingam P,Ganapaty S,Rao ChB

更新日期：2010-01-01 00:00:00

abstract：:The synthesis and biological evaluation of novel human A-FABP inhibitors based on the 6-(trifluoromethyl)pyrimidine-4(1H)-one scaffold is described. Two series of compounds, bearing either an amino or carbon substituent in the 2-position of the pyrimidine ring were investigated. Modification of substituents and chain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ringom R,Axen E,Uppenberg J,Lundbäck T,Rondahl L,Barf T

更新日期：2004-09-06 00:00:00

abstract：:This Letter details our efforts to discover structurally unique M4 PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Temple KJ,Engers JL,Long MF,Watson KJ,Chang S,Luscombe VB,Jenkins MT,Rodriguez AL,Niswender CM,Bridges TM,Conn PJ,Engers DW,Lindsley CW

更新日期：2020-02-01 00:00:00

abstract：:Acetyl CoA carboxylase (ACC) catalyzes the carboxylation of acetyl CoA to form malonyl CoA. In skeletal muscle and heart, malonyl CoA functions to regulate lipid oxidation by inhibition of carnitine palmitoyltransferase-1, an enzyme which controls the entry of long chain fatty acids into mitochondria. We have found th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seng TW,Skillman TR,Yang N,Hammond C

更新日期：2003-10-06 00:00:00

abstract：:The DBU-promoted intramolecular aldol condensation of two partially protected L-lyxo-hexos-5-ulose derivatives (8 and 9), in turn obtained starting from methyl beta-D-galactopyranoside, takes place with fairly good yield and complete diastereoselectivity to give 2L-(2,3,6/4,5)-pentahydroxycyclohexanone derivatives, 10...

journal_title：Bioorganic & medicinal chemistry letters

authors： Catelani G,Corsaro A,D'Andrea F,Mariani M,Pistarà V

更新日期：2002-11-18 00:00:00

abstract：:Twelve dimeric peptidomimetics 1 were prepared via a divergent-convergent strategy. These peptidomimetics incorporated the same amino acids as i +1 and i + 2 residues in key beta-turns of the neurotrophin NT-3. Cytosensor microphysiometry was used to gauge the effects of the dimers 1 on cells that overexpress the NT-3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang AJ,Khare S,Gokulan K,Linthicum DS,Burgess K

更新日期：2001-01-22 00:00:00

abstract：:DNA polymerases can efficiently and sequence selectively incorporate oligonucleotide (ODN)-modified nucleotides and the incorporated oligonucleotide strand can be employed as primer in rolling circle amplification (RCA). The effective amplification of the DNA primer by Φ29 DNA polymerase allows the sequence-selective ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verga D,Welter M,Marx A

更新日期：2016-02-01 00:00:00

abstract：:A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker DP,DeCrescenzo G,Freskos J,Getman DP,Hockerman SL,Li M,Mehta P,Munie GE,Swearingen C

更新日期：2001-10-22 00:00:00

abstract：:A novel series of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec-4-yl]-2-trifluoromethyl-benzonitriles has been synthesized. The ability of these compounds to act as antagonists of the androgen receptor was investigated and several were found to have potent activity in vitro and in vivo. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao HY,Balog A,Attar RM,Fairfax D,Fleming LB,Holst CL,Martin GS,Rossiter LM,Chen J,Cvjic ME,Dell-John J,Geng J,Gottardis MM,Han WC,Nation A,Obermeier M,Rizzo CA,Schweizer L,Spires T Jr,Shan W,Gavai A,Salvati ME

更新日期：2010-08-01 00:00:00

abstract：:Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and stru...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheruvallath Z,Tang M,McBride C,Komandla M,Miura J,Ton-Nu T,Erikson P,Feng J,Farrell P,Lawson JD,Vanderpool D,Wu Y,Dougan DR,Plonowski A,Holub C,Larson C

更新日期：2016-06-15 00:00:00

abstract：:Our internal casein kinase 1ε lead inhibitor, compound 1 was partially cleared by the polymorphic cytochrome P450 2D6. CYP2D6 involvement in metabolism implies more extensive clinical trials. We therefore wanted to reduce the contribution to clearance by this enzyme. We utilized metabolism reports for compound 1 perfo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vaz RJ,Li Y,Metz M,Yang D,Shen H,Munson M

更新日期：2018-12-15 00:00:00

abstract：:Taspase1 is a threonine protease responsible for cleaving MLL (Mixed-Lineage Leukemia) to achieve proper HOX gene expression. Subsequent studies identified additional Taspase1 substrates including Transcription Factor IIA (TFIIA) and Drosophila HCF. Taspase1 is essential for cell proliferation and is overexpressed in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee JT,Chen DY,Yang Z,Ramos AD,Hsieh JJ,Bogyo M

更新日期：2009-09-01 00:00:00

abstract：:A regiochemical and stereochemical mixture of flexible linkers bearing terminal azide functionality was synthesized in two steps from squalene and was used to connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4) ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5-hexyno...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jagadish B,Sankaranarayanan R,Xu L,Richards R,Vagner J,Hruby VJ,Gillies RJ,Mash EA

更新日期：2007-06-15 00:00:00

abstract：:The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leung D,Du W,Hardouin C,Cheng H,Hwang I,Cravatt BF,Boger DL

更新日期：2005-03-01 00:00:00

abstract：:Ceramides are the major lipid components of the stratum corneum, the major permeability barrier of the skin. Here we report a chemical synthesis of ceramide analogs covalently bonded on the silica particles, that can be used to predict the skin permeability of chemicals via HPLC methods. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yin J,Liu H,Pidgeon C

更新日期：1998-01-20 00:00:00

abstract：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00