N1-(2-chloro-benzyl)-N1-ethyl-ethane-1,2-diamine | 61694-80-2

• 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: N1-(2-chloro-benzyl)-N1-ethyl-ethane-1,2-diamine
• 英文别名: N1-(2-chlorobenzyl)-N1-ethylethane-1,2-diamine；N'-[(2-chlorophenyl)methyl]-N'-ethylethane-1,2-diamine
• CAS: 61694-80-2
• 化学式: C₁₁H₁₇ClN₂
• 分子量: 212.722
• InChiKey: CTJGJTKQOVVAKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Ethoxycarbonyl 4-amino-5-chloro-2-methoxybenzoate 、 N1-(2-chloro-benzyl)-N1-ethyl-ethane-1,2-diamine 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-amino-5-chloro-N-[2-[(2-chlorophenyl)methyl-ethylamino]ethyl]-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
• 作为产物：
  描述：

  {2-[(2-chloro-benzyl)-ethyl-amino]-ethyl}carbamic acid benzyl ester 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以95%的产率得到N1-(2-chloro-benzyl)-N1-ethyl-ethane-1,2-diamine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

  摘要：

  Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

  DOI：

  10.1016/s0014-827x(03)00150-2

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：——
• NOVEL MEANS TO MODULATE NMDA RECEPTOR-MEDIATED TOXICITY
  申请人：FUNDAMENTAL PHARMA GMBH

  公开号：US20210347846A1

  公开（公告）日：2021-11-11

  The present invention relates to the field of neurodegenerative processes and means to provide protection against the same. In particular, the present invention relates to polypeptides, fusion proteins, and other compounds interacting with the N-terminal domain of transient receptor potential melastatin subfamily member 4 (TRPM4), which are capable of interfering with NMDA receptor mediated neurotoxicity. The present invention also relates to nucleic acids encoding the aforementioned polypeptides or fusion proteins, compositions comprising the same and the use of said polypeptides, fusion proteins, and other compounds in methods for treating or preventing a disease of the human or animal body, for example in a method of treating diseases like Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) or stroke.
• US4097487A
  申请人：——

  公开号：US4097487A

  公开（公告）日：1978-06-27
• US4197243A
  申请人：——

  公开号：US4197243A

  公开（公告）日：1980-04-08
• 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.