(1R,2R)-N-(cyanomethyl)-2-[4-(3-methoxyphenyl)piperazine-1-carbonyl]cyclohexanecarboxamide | 1403499-35-3

• 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-(cyanomethyl)-2-[4-(3-methoxyphenyl)piperazine-1-carbonyl]cyclohexanecarboxamide
• 英文别名: (1R,2R)-N-(cyanomethyl)-2-[4-(3-methoxyphenyl)piperazine-1-carbonyl]cyclohexane-1-carboxamide
• CAS: 1403499-35-3
• 化学式: C₂₁H₂₈N₄O₃
• 分子量: 384.478
• InChiKey: CUYXSYPJAAXOLP-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  反式-1,2-环己二羧酸酐 、 氨基乙腈盐酸盐 、 1-(3-甲氧基苯基)哌嗪 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 为溶剂， 反应 18.0h， 以8%的产率得到(1R,2R)-N-(cyanomethyl)-2-[4-(3-methoxyphenyl)piperazine-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