ethyl (3R,4R)-1-azabicyclo[2.2.1]heptane-3-carboxylate | 114704-10-8

• 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: ethyl (3R,4R)-1-azabicyclo[2.2.1]heptane-3-carboxylate
• CAS: 114704-10-8；115594-72-4；133366-43-5；133444-97-0；133813-64-6；133813-65-7；134234-17-6；137940-37-5
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: BQNAHLRWSVMSEA-YUMQZZPRSA-N

物化性质

• 沸点：
  219.2±23.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (3R,4R)-1-azabicyclo[2.2.1]heptane-3-carboxylate 在 盐酸 、 氯化亚砜 作用下， 反应 6.5h， 生成 1-氮杂双环[2.2.1]庚烷-3-甲酰氯
  参考文献：
  名称：

  比较氮杂双环酯和恶二唑作为毒蕈碱受体的配体。

  摘要：

  与阿尔茨海默氏型痴呆症相关的认知缺陷与疾病中胆碱能功能的丧失之间的联系为检查毒蕈碱激动剂作为潜在治疗剂提供了基础。本文描述了新型的氮杂双环甲酯作为毒蕈碱受体配体的设计和合成。用3-甲基-1,2,4-恶二唑环取代甲酯可产生有效的代谢更稳定的毒蕈碱激动剂，能够穿透中枢神经系统。这些化合物相对于相应的甲酯通常显示出改善的亲和力。3-甲基1,2,4-恶二唑7b的亲和力是乙酰胆碱的4倍。关于氮杂双环的大小和几何形状以及杂芳族环的电子性质，讨论了受体亲和力。

  DOI：

  10.1021/jm00113a009
• 作为产物：
  描述：

  呋喃并[3,4-c]吡啶-3(1H)-酮 在 palladium on activated charcoal 、 Rh on carbon 氢溴酸 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 ethyl (3R,4R)-1-azabicyclo[2.2.1]heptane-3-carboxylate
  参考文献：
  名称：

  非对映选择性路线和乙基1-氮杂双环[2.2.1]庚-3-基羧酸酯

  摘要：

  非对映选择性路线和乙基1-氮杂双环[2.2.1]庚-3-基羧酸酯（1）和（2）基于同分异构的的溴化氢裂解[4.3.0]双环稠内酯（3）和（4）被描述。

  DOI：

  10.1016/s0040-4039(00)92055-0

文献信息

• Diastereoselective routes to and ethyl 1-azabicyclo[2.2.1] hept-3-YL carboxylates
  作者：Barry S. Orlek、Harry Wadsworth、Paul Wyman、Michael S. Hadley

  DOI：10.1016/s0040-4039(00)92055-0

  日期：1991.2

  Diastereoselective routes to and ethyl 1-azabicyclo[2.2.1]hept-3-yl carboxylates (1) and (2) based on the hydrogen bromide cleavage of the isomeric [4.3.0] bicyclic fused lactones (3) and (4) are described.

  非对映选择性路线和乙基1-氮杂双环[2.2.1]庚-3-基羧酸酯（1）和（2）基于同分异构的的溴化氢裂解[4.3.0]双环稠内酯（3）和（4）被描述。
• Design of [<i>R</i>-(<i>Z</i>)]-(+)-α-(Methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitrile (SB 202026), a Functionally Selective Azabicyclic Muscarinic M1 Agonist Incorporating the <i>N</i>-Methoxy Imidoyl Nitrile Group as a Novel Ester Bioisostere
  作者：Steven M. Bromidge、Frank Brown、Frederick Cassidy、Michael S. G. Clark、Steven Dabbs、Michael S. Hadley、Julie Hawkins、Julia M. Loudon、Christopher B. Naylor、Barry S. Orlek、Graham J. Riley

  DOI：10.1021/jm9702903

  日期：1997.12.1

  Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.
• Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor
  作者：Barry S. Orlek、Frank E. Blaney、Frank Brown、Michael S. G. Clark、Michael S. Hadley、John Hatcher、Graham J. Riley、Howard E. Rosenberg、Harry J. Wadsworth、Paul Wyman

  DOI：10.1021/jm00113a009

  日期：1991.9

  function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents. This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor. Replacement of the methyl ester by a 3-methyl-1,2,4-oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system

  与阿尔茨海默氏型痴呆症相关的认知缺陷与疾病中胆碱能功能的丧失之间的联系为检查毒蕈碱激动剂作为潜在治疗剂提供了基础。本文描述了新型的氮杂双环甲酯作为毒蕈碱受体配体的设计和合成。用3-甲基-1,2,4-恶二唑环取代甲酯可产生有效的代谢更稳定的毒蕈碱激动剂，能够穿透中枢神经系统。这些化合物相对于相应的甲酯通常显示出改善的亲和力。3-甲基1,2,4-恶二唑7b的亲和力是乙酰胆碱的4倍。关于氮杂双环的大小和几何形状以及杂芳族环的电子性质，讨论了受体亲和力。