- Effect of the o-Acetamido Group on pH-Dependent Light Emission of a 3-Hydroxyphenyl-Substituted Dioxetane Luminophore
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A pioneering chemiluminescent molecule reported by Schaap and co-workers, 3-(2′-spiroadamantane)-4-methoxy-4-(3″-hydroxy)phenyl-1,2-dioxetane (AMPD), does not require enzymatic activation but is unsuitable for use under physiological conditions. To overco
- Hisamatsu, Yosuke,Fukiage, Takehiro,Honma, Kojiro,Balia, Andrii G.,Umezawa, Naoki,Kato, Nobuki,Higuchi, Tsunehiko
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Read Online
- Design and Synthesis of a Highly Selective and in Vivo-Capable Inhibitor of the Second Bromodomain of the Bromodomain and Extra Terminal Domain Family of Proteins
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Pan-bromodomain and extra terminal domain (BET) inhibitors interact equipotently with the eight bromodomains of the BET family of proteins and have shown profound efficacy in a number of in vitro phenotypic assays and in vivo pre-clinical models in inflam
- Preston, Alex,Atkinson, Stephen,Bamborough, Paul,Chung, Chun-Wa,Craggs, Peter D.,Gordon, Laurie,Grandi, Paola,Gray, James R. J.,Jones, Emma J.,Lindon, Matthew,Michon, Anne-Marie,Mitchell, Darren J.,Prinjha, Rab K.,Rianjongdee, Francesco,Rioja, Inmaculada,Seal, Jonathan,Taylor, Simon,Wall, Ian,Watson, Robert J.,Woolven, James,Demont, Emmanuel H
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p. 9070 - 9092
(2020/10/19)
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- SUBSTITUTED AMINOTHIAZOLES AS INHIBITORS OF NUCLEASES
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The invention provides compounds represented by the structural formula (1): wherein R1, R2, R3, R4, R5, R6 are as defined in the claims. The compounds are inhibitors of nucleases, and are useful in particular in a method of treatment and/or prevention of proliferative diseases, neurodegenerative diseases, and other genomic instability associated diseases.
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Page/Page column 14; 22-23
(2019/11/12)
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- Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors
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Fe(II)/α-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.
- Jaikhan, Pattaporn,Buranrat, Benjaporn,Itoh, Yukihiro,Chotitumnavee, Jiranan,Kurohara, Takashi,Suzuki, Takayoshi
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supporting information
p. 1173 - 1176
(2019/03/29)
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- ANTIANXIETY DRUGS AND A METHOD OF SCREENING THE SAME
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An anxiolytic drug of the invention comprises an orexin receptor antagonist, a pharmacologically acceptable salt thereof, or a solvate thereof as an active ingredient. A method for screening a compound having an anxiolytic action of the invention comprises a step of using orexin-A.
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Page/Page column 19-20
(2008/06/13)
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- Structural requirements for factor Xa inhibition by 3-oxybenzamides with neutral P1 substituents: Combining X-ray crystallography, 3D-QSAR, and tailored scoring functions
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The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.
- Matter, Hans,Will, David W.,Nazaré, Marc,Schreuder, Herman,Laux, Volker,Wehner, Volkmar
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p. 3290 - 3312
(2007/10/03)
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- NOVEL TRICYCLIC SPIROPIPERIDINES OR SPIROPYRROLIDINES
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The invention provides compounds of formula (I) wherein m, R1, n, R2, q, X, Y, Z, R3, R4, R5, R6, R7, R8, t and R9 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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- Method of inhibiting neoplastic cells with indole derivatives
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A method for inhibiting neoplasia, particularly cancerous and precancerous lesions, by exposing the affected cells to indole derivatives.
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- Indole derivatives as cGMP-PDE inhibitors
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Compounds of the formula (I): STR1 and their pharmaceutically acceptable compositions are useful in inhibiting the activity of cyclic guanosine 3',5'-monophosphate phosphodiesterase.
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