- Synthesis, crystal structure, and antinociceptive effects of some new riluzole derivatives
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Nine N-alkylated derivatives of riluzole were synthesized in order to obtain new compounds with potential antinociceptive activity. Riluzole was firstly transformed into (6-trifluoromethoxy-benzothiazol-2-yl)-hydrazine, then it was chlorinated by SOCl2 to obtain 2-chloro-6-trifluoromethoxy-benzothiazole. This intermediate product was treated with nine alkylamines to give N-alkylated derivatives of riluzole respectively. The structures of compounds were confirmed by means of elemental analysis, IR, 1H NMR, and 13C NMR. The synthetic route was optimized and four novel crystals were obtained by recrystallization. This study investigated the antinociceptive activity of some N-alkylated derivatives of riluzole by hot plate test in mice. The relationship between antinociceptive activity and the doses of 4b, 4c, 4h, 4g, and riluzole had been studied. Compared with the control group (0 mg/kg), the effects of compounds 4b and 4h showed a significant increase (13.78 ± 2.89 s, 12.89 ± 2.94 s, respectively). Compound 4c showed extreme significant increase (18.07 ± 3.08 s) in the time mice spent on the hot plate. The compounds 4b, 4c, and 4h had increased the latency time compared to the blank solvent group. They have potential application in developing new drug candidates with antinociceptive activity.
- Wu, Xiang-Long,Liu, Liu,Li, You-Jia,Luo, Jie,Gai, Dong-Wei,Lu, Ting-Li,Mei, Qi-Bing
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- Deaminative chlorination of aminoheterocycles
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Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)?NH2 can be converted into C(sp2)?Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. [Figure not available: see fulltext.]
- Ghiazza, Clément,Faber, Teresa,Gómez-Palomino, Alejandro,Cornella, Josep
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- NOVEL PIPERAZINES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
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Disclosed are novel piperazine derivatives that act as agonists of the α7 nAChR. Also disclosed are phannaceutical compositions, methods of treating inflammatory conditions, methods of treating CNS disorders, methods for inhibiting cytokine release from mammalian cells and methods for the preparation of the novel compounds.
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Page/Page column 90
(2008/06/13)
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- Preparation and use of aryl alkyl acid derivatives for the treatment of obesity
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This invention relates to certain aryl alkyl acid compounds, compositions, and methods for treating or preventing obesity and related diseases.
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- Propargyl-trifluoromethoxy-amino-benzothiazole derivatives
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The subject invention provides compounds having the structure: wherein R1 is present or absent, and when present is H, C1-C6 alkyl, C1-C6 alkynyl, —(CH2)yS(CH2)x
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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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- Process for the preparation of 2-amino-7-nitrobenzo-thiazoles
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This invention relates to the process for the preparation of 2-amino 7-nitro benzothiazoles of formula (I) STR1 consisting in a) nitrating a derivative of formula (II) STR2 and b) reacting the compound of formula (III) STR3 so obtained with caustic ammonia.
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- Versatile methods for the synthesis of 2-amino-6-trifluoromethoxy-(nitro)benzothiazoles
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Convenient and regioselective syntheses of all three isomers of mononitro-6-trifluoromethoxy-benzothiazoles, starting from 2-amino-6-trifluoromethoxybenzothiazole (riluzole) are described.
- Mignani,Audiau,Le Blevec,Nemecek,Barreau,Jimonet,Gueremy
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p. 2769 - 2780
(2007/10/02)
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- 2-alkyliminobenzothiazoline derivatives, processes for preparing them and medicinal products containing them
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Compounds of formula: STR1 R1 represents a polyfluoroalkoxy radical, R2 represents an alkylthioalkyl, alkylsulphinylalkyl or alkylsulphonylalkyl radical, and R3 represents an alkyl radical, as well as the salts of these compounds with an inorganic or organic acid, processes for preparing them and medicinal products containing them.
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