- Benzimidazole derivatives as well as preparation method and application thereof
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The invention discloses a benzimidazole compound as well as a preparation method and application thereof. The compound has a structure as shown in a formula (I); wherein the X and Y are each independently C or N, R1, R2, R3, R4, A and B are different substituents. The compound is novel in structure and has excellent inhibition effect on the phosphodiesterase 10 type, can effectively selectively suppress the phosphodiesterase 10 type and is free of or is very weak in inhibition effect on other subtype phosphodiesterase; therefore, the compound disclosed by the invention can be used as a phosphodiesterase 10 type inhibitor to be prepared into a medicine for treating and/or preventing related diseases caused by phosphodiesterase 10 type, such as pulmonary hypertension, pulmonary fibrosis, schizophrenia and the like; meanwhile, the benzimidazole compound or the pharmaceutically acceptable salt thereof can be used as a fluorescent probe; for example, the benzimidazole compound or the pharmaceutically acceptable salt thereof can be applied to the aspects of cell imaging, tissue imaging, living body imaging and the like.
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Paragraph 0124-0127
(2020/08/26)
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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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- LACTAM-CONTAINING COMPOUNDS AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS
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The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4—P-M-M4??I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.
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Paragraph 0795
(2017/04/28)
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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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- Structure-activity relationships of anthranilamide-based factor Xa inhibitors containing piperidinone and pyridinone P4 moieties
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Introduction of the phenyl piperidinone and phenyl pyridinone P4 moieties in the anthranilamide scaffold led to potent, selective, and orally bioavailable inhibitors of factor Xa. Anthranilamide 28 displayed comparable efficacy to apixaban in the rabbit a
- Corte, James R.,Fang, Tianan,Pinto, Donald J.P.,Han, Wei,Hu, Zilun,Jiang, Xiang-Jun,Li, Yun-Long,Gauuan, Jolicia F.,Hadden, Mark,Orton, Darren,Rendina, Alan R.,Luettgen, Joseph M.,Wong, Pancras C.,He, Kan,Morin, Paul E.,Chang, Chong-Hwan,Cheney, Daniel L.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.
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p. 2845 - 2849
(2008/12/21)
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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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- AMINOTHIAZOLE DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS
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Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I), where V, W, R1, R2, R3 and R4 are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
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