N-›[2-(n'-benzyl-N'-methylamino)ethyl]-4-amino-5-chloro-2-methoxybenzamide | 61694-61-9

• 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: N-›[2-(n'-benzyl-N'-methylamino)ethyl]-4-amino-5-chloro-2-methoxybenzamide
• 英文别名: N-[2-(N'-benzyl-N'-methylamino)ethyl]-4-amino-5-chloro-2-methoxybenzamide；4-Amino-N-[2-(benzyl-methyl-amino)-ethyl]-5-chloro-2-methoxy-benzamide；4-amino-N-[2-[benzyl(methyl)amino]ethyl]-5-chloro-2-methoxybenzamide
• CAS: 61694-61-9
• 化学式: C₁₈H₂₂ClN₃O₂
• 分子量: 347.845
• InChiKey: VAHDNXLTPLSBHW-UHFFFAOYSA-N

物化性质

• 熔点：
  119-120 °C(Solv: benzene (71-43-2); hexane (110-54-3))
• 沸点：
  481.5±45.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氨基-5-氯-2-甲氧基苯甲酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 N-›[2-(n'-benzyl-N'-methylamino)ethyl]-4-amino-5-chloro-2-methoxybenzamide
  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

• N-1-Benzyl-3-pyrrolidinyl-4-dimethylamino benzamide derivatives
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US04197243A1

  公开（公告）日：1980-04-08

  ##STR1## wherein R represents a hydrogen atom or a lower alkyl group; X represents a lower alkoxy group; Y represents a hydrogen atom, an amino group, or mono- or di-lower alkylamino group; Z represents a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a sulfamoyl group, or a lower alkylsulfamoyl group; said Y and Z may combine to form --N.dbd.N--NH--; W represents a group shown by the formula ##STR2## (wherein A represents a phenyl group, a cyclohexyl group, a furyl group, or a pyridyl group; R.sub.1, R.sub.2, and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a phenyl group; R.sub.3 represents a lower alkyl group, a phenyl lower alkyl group, or a di-lower alkylamino lower alkyl group; R.sub.5, R.sub.6, and R.sub.7, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, or a trifluoromethyl group; R.sub.8 represents a lower alkyl group; and n represents 1 or 2), a 1-ethyl-5-phenyl-2-pyrrolidinylmethyl group, a 1-ethyl-2-isoindolinylmethyl group, a 2-ethyl-1,2,3,4-tetrahydro-4-isoquinolyl group, a 2-(2-phenylpyrrolidino)ethyl group, a 2-(2-isoindolinyl)ethyl group, or a 2-(1,2,3,4-tetrahydro-2-isoquinolyl)ethyl group and the pharmaceutically acceptable nontoxic salts thereof. The compounds of this invention are strong central nervous system depressants, in particular strong antipsychotics.

  其中，R代表氢原子或较低的烷基基团；X代表较低的烷氧基团；Y代表氢原子、氨基团或单或双较低的烷基氨基团；Z代表卤原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚硫氧基团、较低的烷基砜基团、磺胺基团或较低的烷基磺胺基团；所述的Y和Z可以结合形成--N.dbd.N--NH--；W代表由以下公式所示的基团（其中A代表苯基团、环己基团、呋喃基团或吡啶基团；R.sub.1、R.sub.2和R.sub.4，可以相同也可以不同，每个代表氢原子、较低的烷基基团或苯基团；R.sub.3代表较低的烷基基团、苯基较低的烷基基团或双较低的烷基氨基较低的烷基基团；R.sub.5、R.sub.6和R.sub.7，可以相同也可以不同，每个代表氢原子、卤原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚硫氧基团、较低的烷基砜基团、三氟甲基基团；R.sub.8代表较低的烷基基团；n代表1或2），1-乙基-5-苯基-2-吡咯啉基基团，1-乙基-2-异吲哚基基团，2-乙基-1,2,3,4-四氢-4-异喹啉基团，2-(2-苯基吡咯啉基)乙基基团，2-(2-异吲哚基)乙基基团，或2-(1,2,3,4-四氢-2-异喹啉基)乙基基团及其在药学上可接受的无毒盐。本发明的化合物是强大的中枢神经系统抑制剂，特别是强效抗精神病药物。
• Pyrrolidinyl and piperidinyl benzamide derivatives
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US04097487A1

  公开（公告）日：1978-06-27

  ##STR1## wherein R represents a hydrogen atom or a lower alkyl group; X represents a lower alkoxy group; Y represents a hydrogen atom, an amino group, or a mono- or di-lower alkylamino group; Z represents a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a sulfamoyl group, or a lower alkylsulfamoyl group; said Y and Z may combine to form --N.dbd.N--NH--; W represents a group shown by the formula ##STR2## (wherein A represents a phenyl group, a cyclohexyl group, a furyl group, or a pyridyl group; R.sub.1, R.sub.2, and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a phenyl group; R.sub.3 represents a lower alkyl group, a phenyl lower alkyl group, or a di-lower alkylamino lower alkyl group; R.sub.5, R.sub.6, and R.sub.7, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, or a trifluoromethyl group; R.sub.8 represents a lower alkyl group; and n represents 1 or 2), a 1-ethyl-5-phenyl-2-pyrrolidinylmethyl group, a 1-ethyl-2-isoindolinylmethyl group, a 2-ethyl-1,2,3,4-tetrahydro-4-isoquinolyl group, a 2-(2-phenylpyrrolidino)ethyl group, a 2-(2-isoindolinyl)ethyl group, or a 2-(1,2,3,4-tetrahydro-2-isoquinolyl)-ethyl group and the pharmaceutically acceptable nontoxic salts thereof. The compounds of this invention are strong central nervous system depressants, in particular strong antipsychotics.

  其中，R代表氢原子或较低的烷基基团；X代表较低的烷氧基团；Y代表氢原子、氨基团或一种或二种较低烷基氨基团；Z代表卤素原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚砜基团、较低的烷基砜基团、磺酰胺基团或较低的烷基磺酰胺基团；所述的Y和Z可以组合形成--N.dbd.N--NH--；W代表由以下公式所示的基团（其中A代表苯基、环己基、呋喃基或吡啶基；R.sub.1、R.sub.2和R.sub.4，可以相同也可以不同，每个代表氢原子、较低的烷基基团或苯基；R.sub.3代表较低的烷基基团、苯基较低的烷基基团或二烷基氨基较低的烷基基团；R.sub.5、R.sub.6和R.sub.7，可以相同也可以不同，每个代表氢原子、卤素原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚砜基团、较低的烷基砜基团或三氟甲基基团；R.sub.8代表较低的烷基基团；n代表1或2），1-乙基-5-苯基-2-吡咯啉甲基基团，1-乙基-2-异吲哚甲基基团，2-乙基-1,2,3,4-四氢-4-异喹啉基团，2-(2-苯基吡咯啉基团)，2-(2-异吲哚基团)，或2-(1,2,3,4-四氢-2-异喹啉)-乙基基团及其药学上可接受的无毒盐。本发明的化合物是强中枢神经系统抑制剂，特别是强抗精神病药物。
• Benzamides derived from 1,2-diaminocyclopropane as novel ligands for human D 2 and D 3 dopamine receptors
  作者：Donglai Yang、Slaheddine Kefi、Valérie Audinot、Mark-J. Millan、Michel Langlois

  DOI：10.1016/s0968-0896(99)00281-3

  日期：2000.2

  Benzamides (3a-f) derived from 4-amino-5-chloro-2-methoxybenzoic acid and either cis or trans 1,2-diamino cyclopropane were synthesised and were evaluated in binding assays employing, bovine striatal D-2 receptors, recombinant human hD(2) and hD(3) receptors expressed in CHO cells and rat, cortical 5-HT3 and striatal 5-HT4 receptors. The cis and trans isomers of the derivatives were isolated and characterised. The results demonstrated the superiority of the cis conformers over the trans conformers in dopamine receptor binding assays (K-i hD(2) = 13.4 and 6.9 nM and K-i hD(3) = 17.7 and 4.5 nM for the cis-3b and cis-3f compounds, respectively; K-i hD(2) = 816 and >1000 nM and K-i hD(3) = 469 and >1000 nM for the corresponding trans-3b and trans-3f compounds respectively). The cis compounds are folded: the benzamide group and the basic nitrogen atom were in a syn relationship. Compound 3f can be superimposed with a conformation of the tropane derivative, BRL 25594, having the benzyl group in an axial position to give a suitable fit, indicating that both compounds may have a common binding site in the dopamine receptor. (C) 2000 Elsevier Science Ltd. All rights reserved.
• 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：——
• JPS5283621A
  申请人：——

  公开号：JPS5283621A

  公开（公告）日：1977-07-12