N*1*-(4-Chloro-benzyl)-N*1*-isopropyl-ethane-1,2-diamine | 61694-91-5

• 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*1*-(4-Chloro-benzyl)-N*1*-isopropyl-ethane-1,2-diamine
• 英文别名: N'-[(4-chlorophenyl)methyl]-N'-propan-2-ylethane-1,2-diamine
• CAS: 61694-91-5
• 化学式: C₁₂H₁₉ClN₂
• 分子量: 226.749
• InChiKey: JSCCEFNAGHCWEW-UHFFFAOYSA-N

物化性质

• 沸点：
  288.7±20.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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 、 N*1*-(4-Chloro-benzyl)-N*1*-isopropyl-ethane-1,2-diamine 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-amino-5-chloro-N-[2-[(4-chlorophenyl)methyl-propan-2-ylamino]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：

  [(4-Chloro-benzyl)-isopropyl-amino]-acetonitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 1.0h， 生成 N*1*-(4-Chloro-benzyl)-N*1*-isopropyl-ethane-1,2-diamine
  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

• Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif
  作者：Kevin J. Frankowski、Stephen R. Slauson、Kimberly M. Lovell、Angela M. Phillips、John M. Streicher、Lei Zhou、David A. Whipple、Frank J. Schoenen、Thomas E. Prisinzano、Laura M. Bohn、Jeffrey Aubé

  DOI：10.1016/j.bmc.2014.12.033

  日期：2015.7

  sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure–activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo

  通过限制四氢异喹啉部分中磺酰胺氮的优化，使基于磺酰胺的κ阿片受体（KOR）拮抗剂探针分子ML140的效力显着提高。当与其他结构-活性关系探索相结合时，该策略已使该化合物的效力仅比norBNI（一种被广泛使用的KOR拮抗剂工具化合物）低六倍，但合成途径明显更容易。新的优化探针适合用作研究KOR拮抗剂治疗潜力的体内工具。
• 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：——
• 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