5-Chloro-N-(1-ethyl-pyrrolidin-3-yl)-2-methoxy-4-methylamino-benzamide | 78775-20-9

• 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: 5-Chloro-N-(1-ethyl-pyrrolidin-3-yl)-2-methoxy-4-methylamino-benzamide
• 英文别名: 5-chloro-N-(1-ethylpyrrolidin-3-yl)-2-methoxy-4-(methylamino)benzamide
• CAS: 78775-20-9
• 化学式: C₁₅H₂₂ClN₃O₂
• 分子量: 311.812
• InChiKey: GMTJIBBPWHBBFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氯-2-甲氧基-4-甲氨基苯甲酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 5-Chloro-N-(1-ethyl-pyrrolidin-3-yl)-2-methoxy-4-methylamino-benzamide
  参考文献：
  名称：

  Synthesis and neuroleptic activity of benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds

  摘要：

  Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.

  DOI：

  10.1021/jm00142a019

文献信息

• IWANAMI, SUMIO;TAKASHIMA, MUTSUO;HIRATA, YASUFUMI;HASEGAWA, OSAMU;USUDA, +, J. MED. CHEM., 1981, 24, N 10, 1224-1230
  作者：IWANAMI, SUMIO、TAKASHIMA, MUTSUO、HIRATA, YASUFUMI、HASEGAWA, OSAMU、USUDA, +

  DOI：——

  日期：——
• Synthesis and neuroleptic activity of benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds
  作者：Sumio Iwanami、Mutsuo Takashima、Yasufumi Hirata、Osamu Hasegawa、Shinji Usuda

  DOI：10.1021/jm00142a019

  日期：1981.10

  Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.