2-tert-butyl 6-methyl (1R*,4S*,6R*)-2-azabicyclo[2.2.2]octane-2,6-dicarboxylate | 125136-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-tert-butyl 6-methyl (1R*,4S*,6R*)-2-azabicyclo[2.2.2]octane-2,6-dicarboxylate
• 英文别名: (1S,4R,6S)-2-tert-Butyl 6-methyl 2-azabicyclo[2.2.2]octane-2,6-dicarboxylate；2-O-tert-butyl 6-O-methyl (1R,4S,6R)-2-azabicyclo[2.2.2]octane-2,6-dicarboxylate
• CAS: 125136-76-7
• 化学式: C₁₄H₂₃NO₄
• 分子量: 269.341
• InChiKey: VMDDWBSYOBGVND-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-tert-butyl 6-methyl (1R*,4S*,6R*)-2-azabicyclo[2.2.2]octane-2,6-dicarboxylate 在 4 A molecular sieve 、 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 13.33h， 生成 5-[(1R,4S,6R)-2-azabicyclo[2.2.2]octan-6-yl]-3-(1-methylindol-3-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021
• 作为产物：
  描述：

  6-benzyl 2-methyl (1RS,4RS,6RS)-2-azabicyclo[2.2.2]oct-7-ene-2,6-dicarboxylate 在 palladium on activated charcoal 氯化亚砜 、 碘代三甲硅烷 、 氢气 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 145.5h， 生成 2-tert-butyl 6-methyl (1R*,4S*,6R*)-2-azabicyclo[2.2.2]octane-2,6-dicarboxylate
  参考文献：
  名称：

  Stereospecific Synthesis of New 4-Amino-1,2,3-cyclohexanetricarboxylic Acids and 4-Amino-1,3-cyclohexanedicarboxylic Acids

  摘要：

  1,2-二氢吡啶与马来酸和丙烯酸衍生物的Diels-Alder加合物通过RuO4氧化反应，以立体选择性方式转化为新的4-氨基-1,2,3-环己烷三羧酸和4-氨基-1,3-环己烷二羧酸。

  DOI：

  10.1248/cpb.53.81

文献信息

• 3-substituted sulfonyl piperidine derivative
  申请人：MSD K.K.

  公开号：US08188280B2

  公开（公告）日：2012-05-29

  [Problem] There is provided a compound useful as a preventive or remedy for cardiovascular disease, neurologic disease, metabolic disease, reproductive disease, and digestive disease. [Means for Resolution] A compound or a pharmaceutically acceptable salt thereof represented by the following Formula (I) wherein Z represents wherein n1, n2, and n3 are 0, 1, or 2, respectively; R1 represents C1-6 alkyl, C3-8 cycloalkyl, or the like; R2 represents aryl or heteroaryl; R3 represents a hydrogen atom, C1-6 alkyl, or the like; and M1, M2, M3, and M4 independently represent a hydrogen atom, C1-6 alkyl, or the like, or M1, together with M2, M3, or M4, forms —CH2— or the like.

  【问题】提供了一种化合物，可用作心血管疾病、神经疾病、代谢性疾病、生殖疾病和消化疾病的预防或治疗药物。【解决方法】一种化合物或其药学上可接受的盐，其表示如下式（I）：其中Z表示：其中n1，n2和n3分别为0、1或2；R1表示C1-6烷基，C3-8环烷基或类似物；R2表示芳基或杂环芳基；R3表示氢原子，C1-6烷基或类似物；M1、M2、M3和M4分别独立地表示氢原子，C1-6烷基或类似物，或M1与M2、M3或M4一起形成—CH2—或类似物。
• 3-SUBSTITUTED SULFONYL PIPERIDINE DERIVATIVE
  申请人：Nagase Tsuyoshi

  公开号：US20100331360A1

  公开（公告）日：2010-12-30

  [Problem] There is provided a compound useful as a preventive or remedy for cardiovascular disease, neurologic disease, metabolic disease, reproductive disease, and digestive disease. [Means for Resolution] A compound or a pharmaceutically acceptable salt thereof represented by the following Formula (I) wherein Z represents wherein n1, n2, and n3 are 0, 1, or 2, respectively; R 1 represents C 1-6 alkyl, C 3-8 cycloalkyl, or the like; R 2 represents aryl or heteroaryl; R 3 represents a hydrogen atom, C 1-6 alkyl, or the like; and M 1 , M 2 , M 3 , and M 4 independently represent a hydrogen atom, C 1-6 alkyl, or the like, or M 1 , together with M 2 , M 3 , or M 4 , forms —CH 2 — or the like.

  [问题] 提供了一种化合物，可用作心血管疾病、神经疾病、代谢性疾病、生殖疾病和消化疾病的预防或治疗药物。[解决方法] 化合物或其药学上可接受的盐由以下式(I)表示，其中Z代表其中n1、n2和n3分别为0、1或2；R1代表C1-6烷基、C3-8环烷基或类似物；R2代表芳基或杂环芳基；R3代表氢原子、C1-6烷基或类似物；M1、M2、M3和M4独立地表示氢原子、C1-6烷基或类似物，或M1与M2、M3或M4一起形成-CH2-或类似物。
• 3-SUBSTITUTED SULFONYL PIPERAZINE DERIVATIVE
  申请人：MSD K.K.

  公开号：EP2261210B1

  公开（公告）日：2014-10-22
• Novel 5-HT3 antagonists. Indole oxadiazoles
  作者：C. J. Swain、R. Baker、C. Kneen、J. Moseley、J. Saunders、E. M. Seward、G. Stevenson、M. Beer、J. Stanton、K. Watling

  DOI：10.1021/jm00105a021

  日期：1991.1

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.
• Stereospecific Synthesis of New 4-Amino-1,2,3-cyclohexanetricarboxylic Acids and 4-Amino-1,3-cyclohexanedicarboxylic Acids
  作者：Yasushi Arakawa、Manabu Tajima、Yukimi Arakawa、Shigeyuki Yoshifuji

  DOI：10.1248/cpb.53.81

  日期：——

  Diels–Alder adducts of 1,2-dihydropyridine with maleic and acrylic acid derivatives were stereospecifically converted by way of RuO4 oxidation into new 4-amino-1,2,3-cyclohexanetricarboxylic acids and 4-amino-1,3-cyclohexanedicarboxylic acids.

  1,2-二氢吡啶与马来酸和丙烯酸衍生物的Diels-Alder加合物通过RuO4氧化反应，以立体选择性方式转化为新的4-氨基-1,2,3-环己烷三羧酸和4-氨基-1,3-环己烷二羧酸。