2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzoic acid | 561066-99-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzoic acid
• 英文别名: 2-[E-2-(4-Diethylaminomethyl-phenyl)-vinyl]-benzoic acid；2-[(E)-2-[4-(diethylaminomethyl)phenyl]ethenyl]benzoic acid
• CAS: 561066-99-7
• 化学式: C₂₀H₂₃NO₂
• 分子量: 309.408
• InChiKey: IKGWMMYOLFPKFD-BUHFOSPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzoic acid 在 二氯乙酸 、 1-羟基苯并三唑 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 N-(1-benzyl-2-carbamoyl-2-oxo-ethyl)-2-[(E)-2-(4-diethylaminomethylphenyl)vinyl]benzamide
  参考文献：
  名称：

  Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability

  摘要：

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.

  DOI：

  10.1021/jm0210717
• 作为产物：
  描述：

  4-乙烯基-N,N-二乙基苯甲胺 在 palladium diacetate 、 氢氧化钾 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzoic acid
  参考文献：
  名称：

  Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability

  摘要：

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.

  DOI：

  10.1021/jm0210717

文献信息

• Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability
  作者：Wilfried Lubisch、Edith Beckenbach、Sabina Bopp、Hans-Peter Hofmann、Arzu Kartal、Claudia Kästel、Tanja Lindner、Marion Metz-Garrecht、Jutta Reeb、Ferdinand Regner、Michael Vierling、Achim Möller

  DOI：10.1021/jm0210717

  日期：2003.6.1

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.