4-(6-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester | 107618-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-(6-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester
• 英文别名: ethyl 4-(6-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate；ethyl 4-(6-chloro-2-oxo-3H-benzimidazol-1-yl)piperidine-1-carboxylate
• CAS: 107618-38-2
• 化学式: C₁₅H₁₈ClN₃O₃
• 分子量: 323.779
• InChiKey: DUADMNJPVOFXOI-UHFFFAOYSA-N

物化性质

• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(6-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 1-(1-{(R)-3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045
• 作为产物：
  描述：

  4-(5-chloro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester 在 platinum on activated charcoal 甲酸铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-(6-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045

文献信息

• Method for treating allergies using substituted pyrazoles
  申请人：Butler R. Christopher

  公开号：US20050101587A9

  公开（公告）日：2005-05-12

  A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

  使用取代吡唑烷治疗过敏症状的方法，包括特应性过敏症状。
• Substituted pyrazoles
  申请人：Butler R. Christopher

  公开号：US20050245576A1

  公开（公告）日：2005-11-03

  Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

  本文描述了替代吡唑的制备方法、含有它们的组合物以及使用它们治疗由cathepsin S介导的自身免疫性疾病的方法。
• Substituted pyrazoles and methods of treatment with substituted pyrazoles
  申请人：Butler R. Christopher

  公开号：US20070117785A1

  公开（公告）日：2007-05-24

  Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases or allergic conditions, including atopic allergic conditions, mediated by cathepsin S are described.

  本文描述了替代吡唑的制造方法、含有它们的组合物以及使用它们治疗自身免疫性疾病或过敏症的方法，包括由cathepsin S介导的过敏症，例如特应性过敏症。
• Benzimidazolones Which Have Activity at M1 Receptor
  申请人：Budzik Brian

  公开号：US20080306112A1

  公开（公告）日：2008-12-11

  Compounds of formula (I) and salts are provided: wherein R 6 is selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 alkyl substituted with one or more fluorine atoms, C 3-6 cycloalkyl, C 3-6 cycloalkyl substituted with one or more fluorine atoms, C 1-6 alkoxy, C 1-6 alkoxy substituted with one or more fluorine atoms, and cyano, and Q is hydrogen or C 1-6 alkyl. The compounds are M1 agonists and are useful for therapy, for example in the treatment of psychotic disorders and cognitive impairment.

  提供了化学式（I）和盐的化合物：其中R6选择自氢，卤素，C1-6烷基，C1-6烷基取代一个或多个氟原子，C3-6环烷基，C3-6环烷基取代一个或多个氟原子，C1-6烷氧基，C1-6烷氧基取代一个或多个氟原子和氰基，Q为氢或C1-6烷基。这些化合物是M1受体激动剂，可用于治疗精神障碍和认知障碍等疾病。
• Benzimidazolones which have activity at M1 receptor
  申请人：Glaxo Group Limited

  公开号：US08288413B2

  公开（公告）日：2012-10-16

  Compounds of formula (I) and salts are provided: wherein R6 is selected from hydrogen, halogen, C1-6alkyl, C1-6alkyl substituted with one or more fluorine atoms, C3-6cycloalkyl, C3-6cycloalkyl substituted with one or more fluorine atoms, C1-6 alkoxy, C1-6 alkoxy substituted with one or more fluorine atoms, and cyano, and Q is hydrogen or C1-6alkyl. The compounds are M1 agonists and are useful for therapy, for example in the treatment of psychotic disorders and cognitive impairment.

  提供了式（I）化合物和盐： 其中R6从氢，卤素，C1-6烷基，C1-6烷基取代一个或多个氟原子，C3-6环烷基，C3-6环烷基取代一个或多个氟原子，C1-6烷氧基，C1-6烷氧基取代一个或多个氟原子和氰基中选择，Q为氢或C1-6烷基。这些化合物是M1激动剂，并且在治疗精神障碍和认知障碍等方面非常有用。