2-imino-3-(2-(4-phenylpiperazinyl)ethyl)-6-trifluoromethoxybenzothiazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-imino-3-(2-(4-phenylpiperazinyl)ethyl)-6-trifluoromethoxybenzothiazoline
• 英文别名: 3-[2-(4-Phenylpiperazin-1-yl)ethyl]-6-(trifluoromethoxy)-1,3-benzothiazol-2-imine
• 化学式: C₂₀H₂₁F₃N₄OS
• 分子量: 422.474
• InChiKey: ABHUMJXSVVFEPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对三氟甲氧基苯胺 在 吡啶 、 溴 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 50.0h， 生成 2-imino-3-(2-(4-phenylpiperazinyl)ethyl)-6-trifluoromethoxybenzothiazoline
  参考文献：
  名称：

  Riluzole Series. Synthesis and in Vivo “Antiglutamate” Activity of 6-Substituted-2-benzothiazolamines and 3-Substituted-2-imino-benzothiazolines

  摘要：

  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 beta-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-trifluoromethoxybenzothiazlines (61 and 64, ED50 = 10 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.

  DOI：

  10.1021/jm980202u

文献信息

• APPLICATION DE 2-IMINOBENZOTHIAZOLINES DANS LE TRAITEMENT DU PARKINSON ET DES SYNDROMES PARKINSONIENS
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0863756A1

  公开（公告）日：1998-09-16
• [EN] USE OF 2-IMINOBENZOTHIAZOLINES FOR TREATING PARKINSON'S DISEASE AND PARKINSONIAN SYNDROMES<br/>[FR] APPLICATION DE 2-IMINOBENZOTHIAZOLINES DANS LE TRAITEMENT DU PARKINSON ET DES SYNDROMES PARKINSONIENS
  申请人：RHONE-POULENC RORER S.A.

  公开号：WO1997020558A1

  公开（公告）日：1997-06-12

  (EN) The use of 2-iminobenzothiazolines of formula (II), wherein R is a polyfluoroalkoxy or polyfluoroalkyl radical, R1 is a hydrogen atom or a C1-4 alkyl radical, R2 is a 2-propynyl, -alk-S(O)n-alk, -alk-SO2-NH2, -alk-SO2-NHalk or 4-phenylpiperazinylethyl radical, n is 0, 1 or 2 and alk is alkyl, and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof, for treating Parkinson's disease and parkinsonian syndromes, is disclosed.(FR) La présente invention concerne l'application de 2-iminobenzothiazolines de formule (II) dans laquelle R représente un radical polyfluoroalcoxy ou polyfluoroalkyle; R1 représente un atome d'hydrogène ou un radical alkyle (1-4C); R2 représente un radical 2-propynyle, -alk-S(O)n-alk, -alk-SO2-NH2, -alk-SO2-NHalk ou 4-phénylpipérazinyléthyle, n est 0, 1 ou 2 et alk est alkyle, leurs énantiomères, leurs diastéréoisomères et leurs sels pharmaceutiquement acceptables dans le traitement de la maladie de PARKINSON et des syndromes parkinsoniens.
• Riluzole Series. Synthesis and in Vivo “Antiglutamate” Activity of 6-Substituted-2-benzothiazolamines and 3-Substituted-2-imino-benzothiazolines
  作者：Patrick Jimonet、François Audiau、Michel Barreau、Jean-Charles Blanchard、Alain Boireau、Yvette Bour、Marie-Annick Coléno、Adam Doble、Gilles Doerflinger、Claudine Do Huu、Marie-Hélène Donat、Jean Marie Duchesne、Pierre Ganil、Claude Guérémy、Eliane Honoré,、Bernard Just、Roselyne Kerphirique、Sylvie Gontier、Philippe Hubert、Pierre M. Laduron、Joseph Le Blevec、Mireille Meunier、Jean-Marie Miquet、Conception Nemecek、Martine Pasquet、Odile Piot、Jeremy Pratt、Jean Rataud、Michel Reibaud、Jean-Marie Stutzmann、Serge Mignani

  DOI：10.1021/jm980202u

  日期：1999.7.1

  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 beta-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-trifluoromethoxybenzothiazlines (61 and 64, ED50 = 10 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.