- Design, Synthesis, and Biological Evaluation of 4-Phenoxyquinoline Derivatives Containing Benzo[d]thiazole-2-yl Urea as c-Met Kinase Inhibitors
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A series of novel 4-phenoxyquinoline derivatives containing the benzo[d]thiazole-2-yl urea moiety were synthesized and evaluated for their cytotoxicity against the HT-29, MKN-45, and H460 cell lines. The structures of the target compounds were confirmed by 1H NMR and MS spectra. Most of them showed moderate to excellent potency against the three tested cell lines. Especially, compound 23 was identified a promising agent (c-Met IC50 = 17.6 nM), showing the most potent anticancer activities with IC50 values of 0.18, 0.06, and 0.01 μM against the HT-29, MKN-45, and H460 cell lines, respectively. The docking results of 23 with the c-Met kinase model 3LQ8 showed a specific binding mode between the ligand and the target protein.
- Lei, Hongrui,Hu, Gang,Wang, Yu,Han, Pei,Liu, Zijian,Zhao, Yanfang,Gong, Ping
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p. 651 - 661
(2016/08/27)
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- IMIDAZOTHIADIAZOLE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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The present invention provides imidazothiadiazole compounds of Formula (I) wherein A, B, D, Rx, R1, R2, R3, X1, X2 and s are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments.
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Paragraph 00209
(2013/11/18)
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Riluzole series. synthesis and in vivo 'antiglutamate' activity of 6- substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines
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Two series of analogues of riluzole, a blocker of excitatory amino acid mediated neurotransmission, have been synthesized: monosubstituted 2- benzothiazolamines and 3-substituted derivatives. Of all the compounds prepared in the first series, only 2-benzothiazolamines bearing alkyl, polyfluoroalkyl, or polyfluoroalkoxy substituents in the 6-position showed potent anticonvulsant activity against administration of glutamic acid in rats. The most active compounds displaying in vivo 'antiglutamate' activity were the 6-OCF3 (riluzole), 6-OCF2CF3, 6-CF3, and 6-CF2CF3 substituted derivatives with ED50 values between 2.5 and 3.2 mg/kg i.p. Among the second series of variously substituted benzothiazolines, compounds as active as riluzole or up to 3 times more potent were identified in two series: benzothiazolines bearing a β-dialkylaminoethyl moiety and compounds with an alkylthioalkyl chain and their corresponding sulfoxides and sulfones. The most potent derivatives were 2-imino-3-(2-methylthio)- and 2-imino-3-(2- methylsulfinyl)-ethyl-6-trifluoromethoxybenzothiazolines (61 and 64, ED50 = 1.0 and 1.1 mg/kg i.p., respectively). In addition, intraperitoneal administration of some of the best benzothiazolines protected mice from mortality produced by hypobaric hypoxia.
- Jimonet, Patrick,Audiau, Fran?ois,Barreau, Michel,Blanchard, Jean-Charles,Boireau, Alain,Bour, Yvette,Coléno, Marie-Annick,Doble, Adam,Doerflinger, Gilles,Do Huu, Claudine,Donat, Marie-Hélène,Duchesne, Jean Marie,Ganil, Pierre,Guérémy, Claude,Honoré, Eliane,Just, Bernard,Kerphirique, Roselyne,Gontier, Sylvie,Hubert, Philippe,Laduron, Pierre M.,Blevec, Joseph Le,Meunier, Mireille,Miquet, Jean-Marie,Nemecek, Conception,Pasquet, Martine,Piot, Odile,Pratt, Jeremy,Rataud, Jean,Reibaud, Michel,Stutzmann, Jean-Marie,Mignani, Serge
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p. 2828 - 2843
(2007/10/03)
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