Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors.

abstract：:Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Khokhar S,Feng Y,Campitelli MR,Ekins MG,Hooper JN,Beattie KD,Sadowski MC,Nelson CC,Davis RA

更新日期：2014-08-01 00:00:00

abstract：:We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Adva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forsyth T,Kearney PC,Kim BG,Johnson HW,Aay N,Arcalas A,Brown DS,Chan V,Chen J,Du H,Epshteyn S,Galan AA,Huynh TP,Ibrahim MA,Kane B,Koltun ES,Mann G,Meyr LE,Lee MS,Lewis GL,Noguchi RT,Pack M,Ridgway BH,Shi X,

更新日期：2012-12-15 00:00:00

abstract：:A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi MJ,Roh EJ,Hur W,Lee SH,Sim T,Oh CH,Lee SH,Kim JS,Yoo KH

更新日期：2018-12-15 00:00:00

abstract：:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2002-11-04 00:00:00

abstract：:A pilot library of novel 4,4,5,5-tetramethyl-2-(4-substitutedstyrylphenyl)-1,3,2 dioxaborolane derivatives has been synthesized. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide 3 was treated with various aldehydes in the presence of 3 equiv of (t)BuONa in DMF, and stirred at room te...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das BC,Zhao X,Tang XY,Yang F

更新日期：2011-09-15 00:00:00

abstract：:The esterase, phosphatase, and sulfatase activities of carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I, II, and XIII with 4-nitrophenyl esters as substrates was investigated. These enzymes show esterase activity with 4-nitrophenyl acetate as substrate, with second order rate constants in the range of 753-7706M(-1)s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Scozzafava A,Parkkila S,Puccetti L,De Simone G,Supuran CT

更新日期：2008-04-01 00:00:00

abstract：:P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput sc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carter DS,Alam M,Cai H,Dillon MP,Ford AP,Gever JR,Jahangir A,Lin C,Moore AG,Wagner PJ,Zhai Y

更新日期：2009-03-15 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：:Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edgington-Mitchell LE,Barlow N,Aurelio L,Samha A,Szabo M,Graham B,Bunnett N

更新日期：2017-01-15 00:00:00

abstract：:The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of differen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Denhart DJ,Purandare AV,Catt JD,King HD,Gao A,Deskus JA,Poss MA,Stark AD,Torrente JR,Johnson G,Mattson RJ

更新日期：2004-08-16 00:00:00

abstract：:Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage dis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu Y,Marshall J,Li Q,Edwards N,Chen G

更新日期：2013-04-15 00:00:00

abstract：:A group of fluorophore-labeled peptide substrates of Src kinases have been synthesized with the aid of click chemistry. Some of the generated peptides exhibit an increase in fluorescence upon phosphorylation and are capable of detecting Src kinases with high sensitivity and specificity. Their availability permits real...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamaruddin MA,Ung P,Hossain MI,Jarasrassamee B,O'Malley W,Thompson P,Scanlon D,Cheng HC,Graham B

更新日期：2011-01-01 00:00:00

abstract：:Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Passalacqua TG,Dutra LA,de Almeida L,Velásquez AM,Torres FA,Yamasaki PR,dos Santos MB,Regasini LO,Michels PA,Bolzani Vda S,Graminha MA

更新日期：2015-08-15 00:00:00

abstract：:Using simple, inexpensive equipment, we have used solution-phase parallel synthesis to rapidly prepare hundreds of sulfonamide- and urea-containing FKBP inhibitors, resulting in rapid identification of extremely potent compounds in these series. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi C,Li JH,Vaal M,Thomas C,Limburg D,Wu YQ,Chen Y,Soni R,Scott C,Ross DT,Guo H,Howorth P,Valentine H,Liang S,Spicer D,Fuller M,Steiner J,Hamilton GS

更新日期：2002-05-20 00:00:00

abstract：:AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rouse MB,Seefeld MA,Leber JD,McNulty KC,Sun L,Miller WH,Zhang S,Minthorn EA,Concha NO,Choudhry AE,Schaber MD,Heerding DA

更新日期：2009-03-01 00:00:00

abstract：:The synthesis of two C-1 analogues of pancratistatin has been accomplished in 17 steps from bromobenzene. The key steps involved the enzymatic dihydroxylation, regioselective opening of epoxyaziridine 9 with the alane derived from 8, a solid-state silica-gel-catalyzed intramolecular opening of aziridine to produce phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Scattolon J,Hudlicky T,Romero AE,Kornienko A

更新日期：2011-08-15 00:00:00

abstract：:Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu W,Wang Y,Liu S,Yang X,Wang S,Li S,Zhou G,Qin X,Zhou C,Zhang J

更新日期：2013-09-15 00:00:00

abstract：:The aerial parts of Aruncus dioicus var. kamtschaticus afforded five new monoterpenoids (1-5): 4-(erythro-6,7-dihydroxy-9-methylpent-8-enyl)furan-2(5H)-one (1, aruncin A), 2-(8-ethoxy-8-methylpropylidene)-5-hydroxy-3,6-dihydro-2H-pyran-4-carboxylic acid (2, aruncin B), 4-(hydroxymethyl)-6-(8-methylprop-7-enyl)-5,6-dih...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeong SY,Jun do Y,Kim YH,Min BS,Min BK,Woo MH

更新日期：2011-06-01 00:00:00

abstract：:We aimed to discover a novel type of transient receptor potential vanilloid 1 (TRPV1) antagonist because such antagonists are possible drug candidates for treating various disorders. We modified the structure of hit compound 7 (human TRPV1 IC50=411 nM) and converted its pyrrolidino group to a (hydroxyethyl)methylamino...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takahashi E,Hirano N,Nagahara T,Yoshikawa S,Momen S,Yokokawa H,Hayashi R

更新日期：2013-06-01 00:00:00

abstract：:A new immobilization chemistry for covalent attachment of phosphorylated oligonucleotides on epoxy-activated glass surface via opening of oxirane ring is described. The proposed strategy results in excellent immobilization efficiency, spot homogeneity, and morphology. The constructed microarray was successfully demons...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mahajan S,Kumar P,Gupta KC

更新日期：2006-11-01 00:00:00

abstract：:Conformationally restricted analogues of the central linker unit of bacterial methionyl tRNA synthetase (MRS) inhibitors have been prepared. The (1S,2R)-cyclopentylmethyl moiety was identified as the preferred cyclic linker, with significant diastereo- and enantioselectivity of activity. Combination of this linker wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jarvest RL,Berge JM,Brown P,Houge-Frydrych CS,O'Hanlon PJ,McNair DJ,Pope AJ,Rittenhouse S

更新日期：2003-04-07 00:00:00

abstract：:Suzuki cross-coupling has been used to access a wide range of 3- and 5-substituted 2-pyrones, which show remarkable inhibitory activity against bacteria, yeasts and fungi. 3-Octenyl and 5-octenyl 2-pyrones inhibit human ovarium carcinoma (A2780) and human chronic myelogenous leukaemia (K562) cell lines at the micromol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marrison LR,Dickinson JM,Fairlamb IJ

更新日期：2003-08-18 00:00:00

abstract：:Surgical methods guided by exogenous fluorescent markers have the potential to define tissue types in real time. Small molecule dyes with efficient and selective renal clearance could enable visualization of the ureter during surgical procedures involving the abdomen and pelvis. These studies report the design and syn...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cha J,Nani RR,Luciano MP,Kline G,Broch A,Kim K,Namgoong JM,Kulkarni RA,Meier JL,Kim P,Schnermann MJ

更新日期：2018-09-01 00:00:00

abstract：:To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[11C]methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide ([11C]8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miao C,Dong F,Jia L,Li W,Wang M,Zheng QH,Xu Z

更新日期：2019-05-15 00:00:00

abstract：:Two novel α-linked sialyltrisaccharide imidazolium-type probes (ITags) based on the structures of biologically relevant 6'-sialyllactosamine and 3'-sialyllactosamine were efficiently and stereoselectively prepared using a chemo-enzymatic approach. The apparent kinetic parameters for the enzyme catalyzed transformation...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sittel I,Galan MC

更新日期：2015-10-01 00:00:00

abstract：:The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cowart M,Lee CH,Gfesser GA,Bayburt EK,Bhagwat SS,Stewart AO,Yu H,Kohlhaas KL,McGaraughty S,Wismer CT,Mikusa J,Zhu C,Alexander KM,Jarvis MF,Kowaluk EA

更新日期：2001-01-08 00:00:00

abstract：:Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Using active site homology and previous structure-activity relations...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaller MR,Zhong W,Henley C,Magal E,Nguyen T,Powers D,Rzasa RM,Wang W,Xiong X,Norman MH

更新日期：2009-12-01 00:00:00

abstract：:The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein-protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pock...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu S,Gochin M

更新日期：2013-09-15 00:00:00

abstract：:A series of alpha,beta-unsaturated-gamma-lactone-free nitrogen-containing heterocyclic analogues of solamin, a natural mono-THF acetogenin, have been synthesized and their cytotoxicity was investigated against 39 tumor cell lines. One of them, 1-methylpyrazol-5-yl derivative, showed selective increase of cytotoxicity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kojima N,Fushimi T,Maezaki N,Tanaka T,Yamori T

更新日期：2008-03-01 00:00:00

abstract：:This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

更新日期：2007-03-01 00:00:00