- 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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- Nickel-Catalyzed N-Arylation of Primary Amides and Lactams with Activated (Hetero)aryl Electrophiles
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The first nickel-catalyzed N-arylation of amides with (hetero)aryl (pseudo)halides is reported, enabled by use of the air-stable pre-catalyst (PAd-DalPhos)Ni(o-tolyl)Cl (C1). A range of structurally diverse primary amides and lactams were cross-coupled successfully with activated (hetero)aryl chloride, bromide, triflate, tosylate, mesylate, and sulfamate electrophiles.
- Lavoie, Christopher M.,MacQueen, Preston M.,Stradiotto, Mark
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p. 18752 - 18755
(2016/12/26)
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- A general and efficient copper catalyst for the amidation of aryl halides
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An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2-10 mol % of Cul, 5-20 mol % of a 1,2-diamine ligand, and K3PO4, K2CO3, or Cs2CO3 as base. Catalyst systems based on N, N′-dimethylethylenediamine or trans-N,N′-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology.
- Klapars, Artis,Huang, Xiaohua,Buchwald, Stephen L.
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p. 7421 - 7428
(2007/10/03)
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