3-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]propanenitrile | 916993-73-2

• 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: 3-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]propanenitrile
• 英文别名: 3-[2-(3,4-Dimethoxyphenyl)ethyl-methylamino]propanenitrile
• CAS: 916993-73-2
• 化学式: C₁₄H₂₀N₂O₂
• 分子量: 248.325
• InChiKey: IWLGNGUEHPPQHN-UHFFFAOYSA-N

物化性质

• 沸点：
  402.4±40.0 °C(Predicted)
• 密度：
  1.048±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]propanenitrile 在 platinum(IV) oxide 盐酸 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 乙腈 为溶剂， 25.0~70.0 ℃ 、303.98 kPa 条件下， 反应 0.5h， 生成 (E)-4-(4-chlorophenyl)-N-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]but-3-enamide
  参考文献：
  名称：

  Synthesis and Cardiovascular Activity of Phenylalkylamine Derivatives. I. Potential Specific Bradycardic Agents.

  摘要：

  合成了一系列N-(ω-氨基烷基)-N-甲基homoveratrylamine的非环状酰胺衍生物，并评估其在孤立豚鼠右心房中的减心率活性。在这些化合物中，(E)-N-[3-[N'-2-(3, 4-二甲氧基苯)乙基]-N'-甲基氨基]丙基]-4-[3, 4-(亚甲基二氧基)苯]-3-丁酰胺（35）在体外表现出最强的效力，并且在麻醉犬中还发现表现出剂量依赖性的减心率，而对左心室dp/dtmax或平均主动脉压力的显著降低并不明显。

  DOI：

  10.1248/cpb.40.2735
• 作为产物：
  描述：

  β-氯丙腈 、 N-甲基-2-(3,4-二甲氧基苯基)乙胺 在 sodium carbonate 、 sodium iodide 作用下， 以 叔丁醇 为溶剂， 反应 24.0h， 以94%的产率得到3-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]propanenitrile
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

  DOI：

  10.1016/j.bmc.2006.07.055

文献信息

• Crf Receptor Antagonists and Methods
  申请人：Luo Zhiyong

  公开号：US20070293511A1

  公开（公告）日：2007-12-20

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , Y, Ar, and Het are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了具有治疗多种疾病的用途的CRF受体拮抗剂，包括治疗在恒温动物中表现为CRF过度分泌的疾病，如中风。本发明的CRF受体拮抗剂具有以下结构：包括立体异构体、前药和药学上可接受的盐，其中R1、R2、R3、Y、Ar和Het的定义如本文所述。还揭示了含有CRF受体拮抗剂和药学上可接受的载体的组合物，以及使用它们的方法。
• In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450
  作者：Philippe Labrie、Shawn. P. Maddaford、Jacques Lacroix、Concettina Catalano、David K.H. Lee、Suman Rakhit、René C. Gaudreault

  DOI：10.1016/j.bmc.2006.07.055

  日期：2006.12

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.
• Synthesis and Cardiovascular Activity of Phenylalkylamine Derivatives. I. Potential Specific Bradycardic Agents.
  作者：Fumihiro OZAKI、Masayuki MATSUKURA、Yasuhiro KABASAWA、Keiji ISHIBASHI、Megumi IKEMORI、Sachiyuki HAMANO、Norio MINAMI

  DOI：10.1248/cpb.40.2735

  日期：——

  A series of acyclic amide derivatives of N-(ω-aminoalkyl)-N-methylhomoveratrylamine was synthesized and evaluated for their bradycardic activity in isolated guinea pig right atria. Among these compounds, (E)-N-[3-[N'-2-(3, 4-dimethoxyphenyl)ethyl]-N'-methylamino]propyl]-4-[3, 4-(methylenedioxy)phenyl]-3-butenamide (35) was the most potent in vitro and was also found to show dose-dependent bradycardia without remarkable reduction of left ventricular dp/dtmax or mean aortic pressure in anesthetized dogs.

  合成了一系列N-(ω-氨基烷基)-N-甲基homoveratrylamine的非环状酰胺衍生物，并评估其在孤立豚鼠右心房中的减心率活性。在这些化合物中，(E)-N-[3-[N'-2-(3, 4-二甲氧基苯)乙基]-N'-甲基氨基]丙基]-4-[3, 4-(亚甲基二氧基)苯]-3-丁酰胺（35）在体外表现出最强的效力，并且在麻醉犬中还发现表现出剂量依赖性的减心率，而对左心室dp/dtmax或平均主动脉压力的显著降低并不明显。