1,3-Benzenedicarboxylic acid,5-[[[2-(cycloheptylmethyl)-5-phenyl-1H-pyrrol-3-yl]carbonyl]amino]-,bis(phenylmethyl) ester | 869584-11-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,3-Benzenedicarboxylic acid,5-[[[2-(cycloheptylmethyl)-5-phenyl-1H-pyrrol-3-yl]carbonyl]amino]-,bis(phenylmethyl) ester
• 英文别名: 5-[(2-Cycloheptylmethyl-5-phenyl-1H-pyrrole-3-carbonyl)-amino]-isophthalic acid dibenzyl ester
• CAS: 869584-11-2
• 化学式: C₄₁H₄₀N₂O₅
• 分子量: 640.779
• InChiKey: CKLVTPCUIZODAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.16
• 重原子数：
  48.0
• 可旋转键数：
  11.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  97.49
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1,3-Benzenedicarboxylic acid,5-[[[2-(cycloheptylmethyl)-5-phenyl-1H-pyrrol-3-yl]carbonyl]amino]-,bis(phenylmethyl) ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 5-((2-cycloheptylmethyl-5-phenyl-1H-pyrrole-3-carbonyl)amino)isophthalic acid
  参考文献：
  名称：

  Scaffold Hopping with Molecular Field Points:  Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

  摘要：

  A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK2) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK1. In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.

  DOI：

  10.1021/jm049069y
• 作为产物：
  描述：

  4-Cycloheptyl-3-oxo-2-(2-oxo-2-phenyl-ethyl)-butyric acid ethyl ester 在 吡啶 、 sodium hydroxide 、 氯化亚砜 、 ammonium acetate 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1,3-Benzenedicarboxylic acid,5-[[[2-(cycloheptylmethyl)-5-phenyl-1H-pyrrol-3-yl]carbonyl]amino]-,bis(phenylmethyl) ester
  参考文献：
  名称：

  Scaffold Hopping with Molecular Field Points:  Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

  摘要：

  A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK2) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK1. In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.

  DOI：

  10.1021/jm049069y