(1R,2R)-N-(1-cyanocyclopropyl)-2-((R)-2-methyl-4-phenylpiperazine-1-carbonyl)cyclohexanecarboxamide | 1095536-71-2

• 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)-N-(1-cyanocyclopropyl)-2-((R)-2-methyl-4-phenylpiperazine-1-carbonyl)cyclohexanecarboxamide
• 英文别名: (1R,2R)-N-(1-cyanocyclopropyl)-2-[(2R)-2-methyl-4-phenylpiperazine-1-carbonyl]cyclohexane-1-carboxamide
• CAS: 1095536-71-2
• 化学式: C₂₃H₃₀N₄O₂
• 分子量: 394.517
• InChiKey: OQJQSVZAPSMNLA-MISYRCLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-1-N-Boc-2-甲基哌嗪 在 盐酸 、 palladium diacetate 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 、 N,N-二异丙基乙胺 、 sodium t-butanolate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 (1R,2R)-N-(1-cyanocyclopropyl)-2-((R)-2-methyl-4-phenylpiperazine-1-carbonyl)cyclohexanecarboxamide
  参考文献：
  名称：

  Pharmacokinetic Benefits of 3,4-Dimethoxy Substitution of a Phenyl Ring and Design of Isosteres Yielding Orally Available Cathepsin K Inhibitors

  摘要：

  Rational structure-based design has yielded highly potent inhibitors of cathepsin K (Cat K) with excellent physical properties, selectivity profiles, and pharmacokinetics. Compounds with a 3,4-(CH3O)(2)Ph motif, such as 31, were found to have excellent metabolic stability and absorption profiles. Through metabolite identification studies, a reactive metabolite risk was identified with this motif: Subsequent structure-based design of isoteres culminated in the discovery of an optimized and balanced inhibitor (indazole, 38).

  DOI：

  10.1021/jm301119s

文献信息

• Pharmacokinetic Benefits of 3,4-Dimethoxy Substitution of a Phenyl Ring and Design of Isosteres Yielding Orally Available Cathepsin K Inhibitors
  作者：James J. Crawford、Peter W. Kenny、Jonathan Bowyer、Calum R. Cook、Jonathan E. Finlayson、Christine Heyes、Adrian J. Highton、Julian A. Hudson、Anja Jestel、Stephan Krapp、Scott Martin、Philip A. MacFaul、Benjamin P. McDermott、Thomas M. McGuire、Andrew D. Morley、Jeffrey J. Morris、Ken M. Page、Lyn Rosenbrier Ribeiro、Helen Sawney、Stefan Steinbacher、Caroline Smith、Alexander G. Dossetter

  DOI：10.1021/jm301119s

  日期：2012.10.25

  Rational structure-based design has yielded highly potent inhibitors of cathepsin K (Cat K) with excellent physical properties, selectivity profiles, and pharmacokinetics. Compounds with a 3,4-(CH3O)(2)Ph motif, such as 31, were found to have excellent metabolic stability and absorption profiles. Through metabolite identification studies, a reactive metabolite risk was identified with this motif: Subsequent structure-based design of isoteres culminated in the discovery of an optimized and balanced inhibitor (indazole, 38).