Synthesis and evaluation of a cyclic imine derivative conjugated to a fluorescent molecule for labeling of proteins.

abstract：:Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiong H,Brugel TA,Balestra M,Brown DG,Brush KA,Hightower C,Hinkley L,Hoesch V,Kang J,Koether GM,McCauley JP Jr,McLaren FM,Panko LM,Simpson TR,Smith RW,Woods JM,Brockel B,Chhajlani V,Gadient RA,Spear N,Sygowski LA

更新日期：2010-12-15 00:00:00

abstract：:HER2 overexpression is associated with aggressive breast cancer with high recurrence rate and poor patient prognosis. Treatment of HER2 overexpressing patients with the HER2 targeting therapy trastuzumab results in acquired resistance within a year. The HER2/EGFR dual kinase inhibitor lapatinib was shown to inhibit so...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sridhar J,Sfondouris ME,Bratton MR,Nguyen TL,Townley I,Klein Stevens CL,Jones FE

更新日期：2014-01-01 00:00:00

abstract：:Leukotrienes (LT's) are known to play a physiological role in inflammatory immune response. Leukotriene A(4) hydrolase (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to LTB(4). LTB(4) is a known pro-inflammatory mediator. This paper describes the identification and synthe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Eccles W,Blevitt JM,Booker JN,Chrovian CC,Crawford S,de Leon AR,Deng X,Fourie AM,Grice CA,Herman K,Karlsson L,Kearney AM,Lee-Dutra A,Liang J,Luna R,Pippel D,Rao N,Riley JP,Santillán A,Savall B,Tanis VM,Xue X,Y

更新日期：2013-02-01 00:00:00

abstract：:We report the design, synthesis, and structure-activity relationship (SAR) of a series of novel pyrido[2,3-d]pyrimidin-7-one compounds as potent Abl kinase inhibitors. We evaluate their specificity profile against a panel of human recombinant kinases, as well as their biological profile toward a panel of well-characte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antczak C,Veach DR,Ramirez CN,Minchenko MA,Shum D,Calder PA,Frattini MG,Clarkson B,Djaballah H

更新日期：2009-12-15 00:00:00

abstract：:A series of novel tetracyclic core-containing HCV NS5A inhibitors has been discovered. Incorporation of tetrahydropyran-substituted amino acid moiety improved their potency and yielded HCV NS5A inhibitors with a minimum potency shift from the GT1a strain compared to other genotypes and mutants. Compounds 53 and 54 sho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu W,Hu B,Zhong B,Hao J,Lei Z,Agrawal S,Rokosz L,Liu R,Chen S,Asante-Appiah E,Kozlowski JA

更新日期：2019-03-01 00:00:00

abstract：:A small library combining two different benzoquinone cores with seven (L) amino acid methyl esters (alanine, Nomega-nitro-arginine, Nepsilon-BOC-lysine, isoleucine, methionine, phenylalanine and tryptophan) was prepared and tested for prion replication inhibition in ScGT1 cells. The most potent hit, 6a, displayed an E...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran HN,Bongarzone S,Carloni P,Legname G,Bolognesi ML

更新日期：2010-03-15 00:00:00

abstract：:α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evalua...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang JJ,Zhang ZH,He F,Liu XW,Xu XJ,Dai LJ,Liu QM,Yuan M

更新日期：2018-02-15 00:00:00

abstract：:Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring form...

journal_title：Bioorganic & medicinal chemistry letters

authors： Glunz PW,Cheng X,Cheney DL,Weigelt CA,Wei A,Luettgen JM,Wong PC,Wexler RR,Priestley ES

更新日期：2015-01-01 00:00:00

abstract：:Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baba A,Wakao M,Shinchi H,Chan M,Hayashi T,Yao S,Cottam HB,Carson DA,Suda Y

更新日期：2020-02-01 00:00:00

abstract：:The catalytic subunit of the Ser/Thr protein phosphatase 1 (PP1cat) hydrolyses N-acetyl Arg-Arg-Ala-phosphoThr-Val-Ala (K(M) = 3.7 mM) in a reaction that is inhibited competitively by inorganic phosphate (Pi, Ki = 1.6 mM) but unaffected by the product peptide alcohol at concentrations up to 3 mM. The enzyme does not c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanvoisin J,Gani D

更新日期：2001-02-26 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：:Three new iridoid glycosides, 6"-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (2), genipin 1-O-α-D-xylopyranosyl (1→6)-β-D-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known ir...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng K,Yang L,Zhao S,Chen L,Zhao F,Qiu F

更新日期：2013-02-15 00:00:00

abstract：:Seventy-two novel 1,3,4-oxadiazole thioether derivatives containing different flexible-chain moieties were designed and synthesized. The nematicidal activities of all the title compounds were evaluated, and some compounds showed excellent nematicidal activities against citrus nematodes. The compounds 15, 16, 18, 27, 4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Wei C,Wu S,Luo Y,Wu R,Hu D,Song B

更新日期：2020-04-15 00:00:00

abstract：:Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stokes SS,Gowravaram M,Huynh H,Lu M,Mullen GB,Chen B,Albert R,O'Shea TJ,Rooney MT,Hu H,Newman JV,Mills SD

更新日期：2012-01-01 00:00:00

abstract：:A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. All the intermediates and final molecules were characterised using spectral methods and one of the target comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramprasad J,Nayak N,Dalimba U,Yogeeswari P,Sriram D

更新日期：2015-10-01 00:00:00

abstract：:Several p-terphenyl compounds have been isolated from the edible Chinese mushroom Thelephora vialis. Vialinin A, a p-terphenyl compound, strongly inhibits tumor necrosis factor-α production and release. Vialinin A inhibits the enzymatic activity of ubiquitin-specific peptidase 5, one of the target molecules in RBL-2H3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshioka Y,Namiki D,Makiuchi M,Sugaya K,Onose J,Ashida H,Abe N

更新日期：2016-09-01 00:00:00

abstract：:S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hur W,Rosen H,Gray NS

更新日期：2017-01-01 00:00:00

abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Bisai S

更新日期：2005-05-16 00:00:00

abstract：:The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropiset...

journal_title：Bioorganic & medicinal chemistry letters

authors： Macor JE,Gurley D,Lanthorn T,Loch J,Mack RA,Mullen G,Tran O,Wright N,Gordon JC

更新日期：2001-02-12 00:00:00

abstract：:In this study, we synthesized an Azo-py phosphoramidite, featuring azobenzene and pyrene units, as a novel fluorescent and isomeric (trans- and cis-azobenzene units) material, which we incorporated in an i-motif DNA sequence. We then monitored the structural dynamics and changes in fluorescence as the modified DNA seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joo HN,Van Thi Nguyen T,Chae HK,Seo YJ

更新日期：2017-06-01 00:00:00

abstract：:Fast atom bombardment mass spectrometry that can directly analyze lysophospholipids was used to quantitatively determine the kinetics of phospholipase A2. This method is 1250 times more sensitive than the colorimetric assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isomura S,Ito K,Haruna M

更新日期：1999-02-08 00:00:00

abstract：:The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andreu I,Cabedo N,Tormo JR,Bermejo A,Mello R,Cortes D

更新日期：2000-07-03 00:00:00

abstract：:A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 00:00:00

abstract：:Oxomollugin (2) is a degradation product of mollugin (1) and a potent inhibitor of NO-production including nuclear factor kappa B signals. In our endeavor to develop a potent anti-inflammatory compound, we synthesized several aza-derivatives of oxomollugin (2) and evaluated their NO-production inhibitory activity. Aza...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishino H,Nakajima Y,Kakubari Y,Asami N,Deguchi J,Nugroho AE,Hirasawa Y,Kaneda T,Kawasaki Y,Goda Y,Morita H

更新日期：2016-01-15 00:00:00

abstract：:Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adams J,Behnke M,Chen S,Cruickshank AA,Dick LR,Grenier L,Klunder JM,Ma YT,Plamondon L,Stein RL

更新日期：1998-02-17 00:00:00

abstract：:New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raeppel F,Raeppel SL,Therrien E

更新日期：2015-09-15 00:00:00

abstract：:The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

更新日期：2004-08-02 00:00:00

abstract：:A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based on a N-2,4-pyrimidine-N-phenyl-N'-alkyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-alpha production. Two analogs were tested in an in vivo rat iodoacetate m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maier JA,Brugel TA,Clark MP,Sabat M,Golebiowski A,Bookland RG,Laufersweiler MJ,Laughlin SK,Vanrens JC,De B,Hsieh LC,Brown KK,Juergens K,Walter RL,Janusz MJ

更新日期：2006-07-01 00:00:00

abstract：:4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Golebiowski A,Townes JA,Laufersweiler MJ,Brugel TA,Clark MP,Clark CM,Djung JF,Laughlin SK,Sabat MP,Bookland RG,VanRens JC,De B,Hsieh LC,Janusz MJ,Walter RL,Webster ME,Mekel MJ

更新日期：2005-05-02 00:00:00

abstract：:In this study, we synthesized a series of enantiomerically pure (2R,3S)-disubstituted tetrahydropyranes with diverse functional groups using known methodologies. In addition to the tert-butyl dimethyl silyl group, other common protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were used to obta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donadel OJ,Martín T,Martín VS,Villar J,Padrón JM

更新日期：2005-08-01 00:00:00