4-piperidinone 4-methanesulfonylphenylhydrazone monohydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-piperidinone 4-methanesulfonylphenylhydrazone monohydrochloride
• 英文别名: 4-methylsulfonyl-N-(4-piperidylideneamino)aniline hydrochloride；4-Methylsulfonyl-N-(4-piperidylideneamino)aniline hydrochloride；4-methylsulfonyl-N-(piperidin-4-ylideneamino)aniline;hydrochloride
• 化学式: C₁₂H₁₇N₃O₂S*ClH
• 分子量: 303.813
• InChiKey: LXYXINYXWHZIPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  78.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-piperidinone 4-methanesulfonylphenylhydrazone monohydrochloride 在 三氟化硼乙醚 、 溶剂黄146 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (1R,2R)-N-(1-cyanocyclopropyl)-2-{[8-(methylsulfonyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxamide
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 4-甲磺酰基苯肼盐酸盐 在 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以96%的产率得到4-piperidinone 4-methanesulfonylphenylhydrazone monohydrochloride
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257

文献信息

• Novel Compound - 827
  申请人：Dossetter Alexander Graham

  公开号：US20090012077A1

  公开（公告）日：2009-01-08

  The present invention relates to compounds and compositions for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases, including cathepsins B, K, C, F, H, L, O, S, W and X. Of particular interest are diseases associated with Cathepsin K.

  本发明涉及用于治疗与半胱氨酸蛋白酶活性相关疾病的化合物和组合物。这些化合物是半胱氨酸蛋白酶的可逆抑制剂，包括卡特普辛B、K、C、F、H、L、O、S、W和X。特别感兴趣的是与卡特普辛K相关的疾病。
• Synthesis of 8-substituted tetrahydro-γ-carbolines
  作者：Alexandre Bridoux、Laurence Goossens、Raymond Houssin、Jean-Pierre Héanichart

  DOI：10.1002/jhet.5570430308

  日期：2006.5

  The Fischer reaction is applied to the synthesis of 8-substituted tetrahydro-γ-carbolines with electron-donating or electron-withdrawing groups, using catalytic or thermal methods. The reaction conditions must be varied according to the nature of the N 1 substituent of the piperidone. The best results are observed when a releasing group is present on the arylhydrazine and a benzyl substituent on the

  使用催化或热方法，将Fischer反应应用于具有供电子或吸电子基团的8-取代的四氢-γ-咔啉的合成。反应条件必须根据哌啶酮的N 1取代基的性质而变化。当芳基肼上的释放基团和哌啶酮的氮上的苄基取代基存在时，观察到最好的结果。在软酸性条件下观察到带有取代基的咔啉的形成；在其他情况下，反应在ended水平结束或没有发生。
• 1-CYANOCYCLOPROPYL-DERIVATIVES AS CATHEPSIN K INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP2170879B1

  公开（公告）日：2013-01-16
• US8008279B2
  申请人：——

  公开号：US8008279B2

  公开（公告）日：2011-08-30
• (1<i>R</i>,2<i>R</i>)-<i>N</i>-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-<i>b</i>]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis
  作者：Alexander G. Dossetter、Howard Beeley、Jonathan Bowyer、Calum R. Cook、James J. Crawford、Jonathan E. Finlayson、Nicola M. Heron、Christine Heyes、Adrian J. Highton、Julian A. Hudson、Anja Jestel、Peter W. Kenny、Stephan Krapp、Scott Martin、Philip A. MacFaul、Thomas M. McGuire、Pablo Morentin Gutierrez、Andrew D. Morley、Jeffrey J. Morris、Ken M. Page、Lyn Rosenbrier Ribeiro、Helen Sawney、Stefan Steinbacher、Caroline Smith、Madeleine Vickers

  DOI：10.1021/jm3007257

  日期：2012.7.26

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.