吗丁啉杂质12 | 107618-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 吗丁啉杂质12
• 英文名称: ethyl 4-[(2-amino-5-chlorophenyl)amino]-1-piperidinecarboxylate
• 英文别名: ethyl 4-(2-amino-5-chloroanilino)piperidine-1-carboxylate
• CAS: 107618-26-8
• 化学式: C₁₄H₂₀ClN₃O₂
• 分子量: 297.785
• InChiKey: GUUXGSRAESAWJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  吗丁啉杂质12 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 6-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-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-氨基-1-哌啶甲酸乙酯 在 镍 氢气 、 sodium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 29.0h， 生成 吗丁啉杂质12
  参考文献：
  名称：

  Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimidazolone derivatives

  摘要：

  A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.

  DOI：

  10.1021/jm00388a012

文献信息

• 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。
• WO2007/36711
  申请人：——

  公开号：——

  公开（公告）日：——
• HENNING R.; LATTRELL R.; GARHARDS H. J.; LEVEN M., J. MED. CHEM., 30,(1987) N 5, 814-819
  作者：HENNING R.、 LATTRELL R.、 GARHARDS H. J.、 LEVEN M.

  DOI：——

  日期：——
• BENZIMIDAZOLONES WHICH HAVE ACTIVITY AT M1 RECEPTOR
  申请人：GLAXO GROUP LIMITED

  公开号：EP1937670A1

  公开（公告）日：2008-07-02