2-(diethylamino)ethyl 1-[p-(1-pyrrolidinyl)phenyl]cyclopentanecarboxylate | 135569-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-(diethylamino)ethyl 1-[p-(1-pyrrolidinyl)phenyl]cyclopentanecarboxylate
• 英文别名: 2-(diethylamino)ethyl 1-(p-1-pyrrolidinylphenyl)cyclopentanecarboxylate；1-(4-Pyrrolidin-1-yl-phenyl)-cyclopentanecarboxylic acid 2-diethylamino-ethyl ester; hydrochloride；2-(diethylamino)ethyl 1-(4-pyrrolidin-1-ylphenyl)cyclopentane-1-carboxylate
• CAS: 135569-23-2
• 化学式: C₂₂H₃₄N₂O₂
• 分子量: 358.524
• InChiKey: PXBMYTXCOCGUQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-nitro-phenyl)-cyclopentanecarbonyl chloride 在 platinum on activated charcoal 氢气 、 sodium 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 36.0h， 生成 2-(diethylamino)ethyl 1-[p-(1-pyrrolidinyl)phenyl]cyclopentanecarboxylate
  参考文献：
  名称：

  Muscarinic receptor binding profile of para-substituted caramiphen analogs

  摘要：

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).

  DOI：

  10.1021/jm00114a005

文献信息

• Muscarinic receptor binding profile of para-substituted caramiphen analogs
  作者：Robert L. Hudkins、Diane L. DeHaven-Hudkins、James F. Stubbins

  DOI：10.1021/jm00114a005

  日期：1991.10

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).