(1R,2R)-2-[(4-methylpiperazin-1-yl)carbonyl]-1-cyclohexanecarboxylic acid | 318280-90-9

• 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: (1R,2R)-2-[(4-methylpiperazin-1-yl)carbonyl]-1-cyclohexanecarboxylic acid
• 英文别名: (1R,2R)-2-(4-methylpiperazin-4-ium-1-carbonyl)cyclohexane-1-carboxylate
• CAS: 318280-90-9
• 化学式: C₁₃H₂₂N₂O₃
• 分子量: 254.329
• InChiKey: XKZDSAVFHPKHNV-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-[(4-methylpiperazin-1-yl)carbonyl]-1-cyclohexanecarboxylic acid 、 氨基乙腈盐酸盐 在 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， 以17%的产率得到(1R,2R)-N-(cyanomethyl)-2-(4-methylpiperazine-1-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：

  (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid 在 乙酸酐 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (1R,2R)-2-[(4-methylpiperazin-1-yl)carbonyl]-1-cyclohexanecarboxylic acid
  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

• Streptogramin derivatives, their preparation and compositions containing them
  申请人：Aventis Pharma S.A.

  公开号：US06569854B1

  公开（公告）日：2003-05-27

  Group A streptogramin derivatives of general formula (I) in which: R1 represents a halogen atom or an azido or thiocyanato radical, R2 represents a hydrogen atom or a methyl or ethyl radical, R3 represents a hydrogen atom, or the residue of an aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic or heterocyclylaliphatic ester which may be substituted, and the bond - - - represents a single bond (stereochemistry 27R) or a double bond, as well as its salts when they exist.

  通用公式（I）中的A组链霉素衍生物，其中： R1代表卤素原子或偶氮基或硫氰基， R2代表氢原子或甲基或乙基基， R3代表氢原子，或脂肪、环脂、芳香、芳基脂肪、杂环或杂环脂肪酯的残基，可能被取代， 连接- - - 代表单键（立体化学27R）或双键， 以及存在时的盐。
• US7166594B2
  申请人：——

  公开号：US7166594B2

  公开（公告）日：2007-01-23
• (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.