DL-α-methyl-3-(2-naphthyl)alanine methyl ester | 143004-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: DL-α-methyl-3-(2-naphthyl)alanine methyl ester
• 英文别名: Methyl 2-amino-2-methyl-3-naphthalen-2-ylpropanoate
• CAS: 143004-78-8
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: VQRFJJGBBKYJKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  DL-α-methyl-3-(2-naphthyl)alanine methyl ester 在 lithium hydroxide 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 2.0h， 生成 [2-(2-Adamantyloxycarbonylamino)-2-methyl-3-naphthalen-2-ylpropanoyl] 2-(2-adamantyloxycarbonylamino)-2-methyl-3-naphthalen-2-ylpropanoate
  参考文献：
  名称：

  Cholecystokinin peptidomimetics as selective CCK-B antagonists: Design, synthesis, and in vitro and in vivo biochemical properties

  摘要：

  Antagonists of cholecystokinin-B (CCK-B) receptors have been shown to alleviate CCK4-induced panic attacks in humans and to potentiate opioid effects in animals. The clinical use of these compounds is critically dependent on their ability to cross the blood-brain barrier. In order to improve this property, new, peptoid-derived CCK-B antagonists, endowed with high affinity, selectivity, and increased lipophilicity have been developed. The affinity and selectivity of these compounds have been characterized in vitro and in vivo using guinea pig, rat, and mouse. Most of these compounds proved to be selective for the CCK-B receptor, the most potent analog, N-[N-[(2-adamantyloxy)carbonyl]-D-alpha-methyltryptophanyl]-N-[2-(4-chlorophenyl)ethyl]glycine (26A), having a K(i) value of 6.1 nM for guinea pig cortex membranes in vitro and a good selectivity ratio (K(i) CCK-A/K(i) CCK-B = 174). Furthermore, the in vivo affinity of 26A for mouse brain CCK-B receptors, following intracerebroventricular injection at different concentrations, was found to be 10 nmol. Using competition experiments with the specific CCK-B ligand [H-3]pBC 264, compound 26A was shown to cross the blood-brain barrier (0.2%) after intraperitoneal administration in mice. This compound is therefore an interesting pharmacological tool to further elucidate the physiopathological role of endogenous CCK.

  DOI：

  10.1021/jm00072a005
• 作为产物：
  描述：

  Methyl 2-(benzylideneamino)-2-methyl-3-naphthalen-2-ylpropanoate 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 DL-α-methyl-3-(2-naphthyl)alanine methyl ester
  参考文献：
  名称：

  Cholecystokinin peptidomimetics as selective CCK-B antagonists: Design, synthesis, and in vitro and in vivo biochemical properties

  摘要：

  Antagonists of cholecystokinin-B (CCK-B) receptors have been shown to alleviate CCK4-induced panic attacks in humans and to potentiate opioid effects in animals. The clinical use of these compounds is critically dependent on their ability to cross the blood-brain barrier. In order to improve this property, new, peptoid-derived CCK-B antagonists, endowed with high affinity, selectivity, and increased lipophilicity have been developed. The affinity and selectivity of these compounds have been characterized in vitro and in vivo using guinea pig, rat, and mouse. Most of these compounds proved to be selective for the CCK-B receptor, the most potent analog, N-[N-[(2-adamantyloxy)carbonyl]-D-alpha-methyltryptophanyl]-N-[2-(4-chlorophenyl)ethyl]glycine (26A), having a K(i) value of 6.1 nM for guinea pig cortex membranes in vitro and a good selectivity ratio (K(i) CCK-A/K(i) CCK-B = 174). Furthermore, the in vivo affinity of 26A for mouse brain CCK-B receptors, following intracerebroventricular injection at different concentrations, was found to be 10 nmol. Using competition experiments with the specific CCK-B ligand [H-3]pBC 264, compound 26A was shown to cross the blood-brain barrier (0.2%) after intraperitoneal administration in mice. This compound is therefore an interesting pharmacological tool to further elucidate the physiopathological role of endogenous CCK.

  DOI：

  10.1021/jm00072a005

文献信息

• Cholecystokinin peptidomimetics as selective CCK-B antagonists: Design, synthesis, and in vitro and in vivo biochemical properties
  作者：Armand G. S. Blommaert、Jian Hui Weng、Agnes Dorville、Isabelle McCort、Bertrand Ducos、Christine Durieux、Bernard P. Roques

  DOI：10.1021/jm00072a005

  日期：1993.10

  Antagonists of cholecystokinin-B (CCK-B) receptors have been shown to alleviate CCK4-induced panic attacks in humans and to potentiate opioid effects in animals. The clinical use of these compounds is critically dependent on their ability to cross the blood-brain barrier. In order to improve this property, new, peptoid-derived CCK-B antagonists, endowed with high affinity, selectivity, and increased lipophilicity have been developed. The affinity and selectivity of these compounds have been characterized in vitro and in vivo using guinea pig, rat, and mouse. Most of these compounds proved to be selective for the CCK-B receptor, the most potent analog, N-[N-[(2-adamantyloxy)carbonyl]-D-alpha-methyltryptophanyl]-N-[2-(4-chlorophenyl)ethyl]glycine (26A), having a K(i) value of 6.1 nM for guinea pig cortex membranes in vitro and a good selectivity ratio (K(i) CCK-A/K(i) CCK-B = 174). Furthermore, the in vivo affinity of 26A for mouse brain CCK-B receptors, following intracerebroventricular injection at different concentrations, was found to be 10 nmol. Using competition experiments with the specific CCK-B ligand [H-3]pBC 264, compound 26A was shown to cross the blood-brain barrier (0.2%) after intraperitoneal administration in mice. This compound is therefore an interesting pharmacological tool to further elucidate the physiopathological role of endogenous CCK.