- Ring size changes in the development of class I HDAC inhibitors
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Five pathways involving different ring structures led to generation of fourteen thienylbenzamides (7–20) which display the structure-activity relationships of class I HDAC inhibitors. All the synthesised compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound. Compounds 8 and 16 inhibit HCT116 cells by activation of the apoptosis pathway.
- Cho, Er-Chieh,Liu, Chi-Yuan,Tang, Di-Wei,Lee, Hsueh-Yun
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p. 1387 - 1401
(2021/07/06)
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- Design, synthesis and biological evaluation of anthranilamide derivatives as potential factor Xa (fXa) inhibitors
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Factor Xa (fXa) is a crucial player in various thromboembolic disorders. Inhibition of fXa can provide safe and effective antithrombotic effects. In this study, a series of anthranilamide compounds were designed by utilizing structure-based design strategies. Optimization at P1 and P4 groups led to the discovery of compound 16g: a highly potent, selective fXa inhibitor with pronounced in vitro anticoagulant activity. Moreover, 16g also displayed excellent in vivo antithrombotic activity in the rat venous thrombosis (VT) and arteriovenous shunt (AV-SHUNT) models. The bleeding risk evaluation showed that 16g had a safer profile than that of betrixaban at 1 mg/kg and 5 mg/kg dose. Additionally, 16g also exhibited satisfactory PK profiles. Eventually, 16g was selected to investigate its effect on hypoxia-reoxygenation- induced H9C2 cell viability. MTT results showed that H9C2 cell viability can be remarkably alleviated by 16g.
- Xing, Junhao,Yang, Lingyun,Zhou, Jinpei,Zhang, Huibin
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p. 5987 - 5999
(2018/11/23)
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- 3,4-dibenzamido benzamide derivative, preparation method and application thereof
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The invention discloses a 3,4-dibenzamido benzamide derivative (I), wherein R1, R2 and R3 are respectively and individually hydrogen, fluorine, chlorine, bromine, hydroxyl groups, alkoxy groups, amino groups or substituted amino groups. The alkoxy groups
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- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-COA DESATURASE
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The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
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Page/Page column 34
(2010/07/04)
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- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
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The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
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Page/Page column 90
(2009/10/01)
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- SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa
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In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiam
- Qiao, Jennifer X.,Chang, Chong-Hwan,Cheney, Daniel L.,Morin, Paul E.,Wang, Gren Z.,King, Sarah R.,Wang, Tammy C.,Rendina, Alan R.,Luettgen, Joseph M.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.
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p. 4419 - 4427
(2008/02/10)
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- PROCESS FOR PRODUCING 3-ACYLAMINOBENZOFURAN-2-CARBOXYLIC ACID DERIVATIVE
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The present invention provides a process of preparing a compound of the formula [I]: wherein X is a group of the formula: -N="or" -CH=; R1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a cyano group or an amino group optionally substituted by a lower alkyl group; Ring A is a nitrogen-containing heterocyclic group; Ring B is an optionally substituted benzene ring or an optionally substituted pyridine ring; and R3 is a hydrogen atom or a lower alkyl group, or a pharmaceutically acceptable salt thereof , which is useful as an inhibitor of activated blood coagulation factor X.
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Page/Page column 18
(2008/06/13)
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- NOVEL CARBOXAMIDES FOR USE AS XA INHIBITORS
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The invention relates to the novel substituted carboxamides of general formula (I), wherein A, B and R1 to R5 are defined as in claim 1, the tautomers, enantiomers, diastereomers, mixtures and salts thereof, especially the physiologically salts thereof with inorganic or organic acids or bases, which have valuable properties. The inventive compounds have an antithrombotic effect and are factor Xa inhibitors.
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Page/Page column 99-100
(2010/02/13)
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- New carboxylic acid amides, the preparation thereof and their use as medicaments
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The present invention relates to new substituted carboxylic acid amides of general formula wherein A, B and R1 to R5 are defined as in claim 1, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.
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Page/Page column 34
(2010/02/13)
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- Pyrrolidin-2-one compounds and their use as neuraminidase inhibitors
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A compound having the formula: wherein all variables are as defined in the specification, for use as a neuramninidase inhibitor.
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- Potent inhibition of influenza sialidase by a benzoic acid containing a 2-pyrrolidinone substituent
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On the basis of the lead compound 4-(N-acetylamino)-3-guanidinobenzoic acid (BANA 113), which inhibits influenza A sialidase with a K(i) of 2.5 μM, several novel aromatic inhibitors of influenza sialidases were designed. In this study the N-acetyl group of BANA 113 was replaced with a 2- pyrrolidinone ring, which was designed in part to offer opportunities for introduction of spatially directed side chains that could potentially interact with the 4-, 5-, and/or 6-subsites of sialidase. While the parent structure 1-(4-carboxy-2-guanidinophenyl)pyrrolidin-2-one (8) was only a modest inhibitor of sialidase, the introduction of a hydroxymethyl or bis(hydroxymethyl) substituent at the C5' position of the 2-pyrrolidinone ring resulted in inhibitors (9 and 12, respectively) with low micromolar activity. Crystal structures of these inhibitors in complex with sialidase demonstrated that the substituents at the 5'-position of the 2-pyrrolidinone ring interact in the 4- and/or 5-subsites of the enzyme. Replacement of the guanidine in 12 with a hydrophobic 3-pentylamino group resulted in a large enhancement in binding to produce an inhibitor (14) with an IC50 of about 50 nM against influenza A sialidase, although the inhibition of influenza B sialidase was 2000-fold less. This represents the first reported example of a simple, achiral benzoic acid with potent (low nanomolar) activity as an inhibitor of influenza sialidase.
- Atigadda, Venkatram R.,Brouillette, Wayne J.,Duarte, Franco,Ali, Shoukath M.,Babu, Yarlagadda S.,Bantia, Shanta,Chand, Pooran,Chu, Naiming,Montgomery, John A.,Walsh, David A.,Sudbeck, Elise A.,Finley, James,Luo, Ming,Air, Gillian M.,Laver, Graeme W.
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p. 2332 - 2343
(2007/10/03)
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- Potential Antiatherosclerotic Agents. 4. benzoic Acid Analogues of Cetaben
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The synthesis of a series of analogues in which the alkyl group of cetaben is substituted with various functional groups or replaced entirely by a functionalized alkanoyl moiety is described.Also reported are the syntheses of branched-chain (alkylamino)be
- DeVries, Vern G.,Largis, Elwood E.,Miner, Thomas G.,Shepherd, Robert G.,Upeslacis, Janis
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p. 1411 - 1421
(2007/10/02)
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