1-(3-Brom-propoxy)-3,4-dimethoxy-benzol | 3351-57-3

• 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: 1-(3-Brom-propoxy)-3,4-dimethoxy-benzol
• 英文别名: 1-(3-Bromopropoxy)-3,4-dimethoxybenzene；4-(3-bromopropoxy)-1,2-dimethoxybenzene
• CAS: 3351-57-3
• 化学式: C₁₁H₁₅BrO₃
• 分子量: 275.142
• InChiKey: LKEVWVMDGMJQQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-Brom-propoxy)-3,4-dimethoxy-benzol 在 N,N-二异丙基乙胺 、 O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-(3-(3,4-dimethoxyphenoxy)propyl)-2-(2-(4-methoxyphenyl)-2-oxoethyl)-N-methylpyrimidine-5-carboxamide
  参考文献：
  名称：

  作为乙酰胆碱酯酶抑制剂的 2-(2-氧乙基)嘧啶-5-甲酰胺衍生物的设计、合成和评价

  摘要：

  设计、合成和评估了一系列新的 2-(2-氧代乙基)嘧啶-5-甲酰胺衍生物作为治疗阿尔茨海默病 (AD) 的乙酰胆碱酯酶抑制剂 (AChEI)。生物活性结果表明，化合物10q对AChE的抑制活性最好（IC 50  = 0.88 ± 0.78 μM），优于石杉碱甲，对BuChE的抑制作用较弱（IC 50  = 10.0 ± 1.30 μM ） )，这表明化合物10q是主要的 AChE 抑制剂。此外，分子对接研究结果显示，10q可以同时与 AChE 的 CAS 和 PAS 位点结合，这与10q的酶动力学研究显示的混合抑制模式一致。此外，利用molinspiration server和pkCSM对目标化合物的分子性质进行了在线预测，结果表明化合物10q具有满足Lipinski五法则的类药物性质。基于生物活性和分子特性，进一步开发的化合物10q是有价值的。

  DOI：

  10.1016/j.bmcl.2022.128873
• 作为产物：
  描述：

  3,4-二甲氧基苯酚 、 1,3-二溴丙烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 1-(3-Brom-propoxy)-3,4-dimethoxy-benzol
  参考文献：
  名称：

  （+/-）-2-（3-哌啶基）-1,2,3,4-四氢异喹啉是一类新型的特异性缓动性心脏病。

  摘要：

  制备了一系列（+/-）-2-（3-哌啶基）-1，2，3，4-四氢异喹啉，并在分离的豚鼠右心房和麻醉大鼠中检查了它们的心动过缓。对母体化合物1的苄基部分进行的修饰导致将化合物11e鉴定为有效的特定缓激药。

  DOI：

  10.1016/s0960-894x(03)00349-4

文献信息

• (±)-2-(3-Piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific bradycardic agents
  作者：Hideki Kubota、Akio Kakefuda、Toshihiro Watanabe、Yasuko Taguchi、Noe Ishii、Noriyuki Masuda、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/s0960-894x(03)00349-4

  日期：2003.7

  A series of (+/-)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines were prepared and their bradycardic activities were examined in isolated guinea-pigs' right atria and in anesthetized rats. Modifications on the benzyl moiety of the parent compound, 1, led to the identification of compound 11e as a potent and specific bradycardic agent.

  制备了一系列（+/-）-2-（3-哌啶基）-1，2，3，4-四氢异喹啉，并在分离的豚鼠右心房和麻醉大鼠中检查了它们的心动过缓。对母体化合物1的苄基部分进行的修饰导致将化合物11e鉴定为有效的特定缓激药。
• Some Cardiovascular Effects of a Series of Aryloxyalkylamines. I
  作者：J. Augstein、W. C. Austin、R. J. Boscott、S. M. Green、C. R. Worthing

  DOI：10.1021/jm00327a017

  日期：1965.5
• Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4- tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing I_f Channel Inhibitory Activity
  作者：Hideki Kubota、Akio Kakefuda、Toshihiro Watanabe、Noe Ishii、Koichi Wada、Noriyuki Masuda、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1021/jm0301742

  日期：2003.10.1

  A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (+/-)-6,7-Dimethoxy-2-1-[3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3,4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against I-f currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of I-f currents (IC50 = 0.32 muM) in guinea pig pacemaker cells.
• Synthesis and pharmacological evaluation of N -acyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents
  作者：Hideki Kubota、Toshihiro Watanabe、Akio Kakefuda、Noriyuki Masuda、Kouichi Wada、Noe Ishii、Shuichi Sakamoto、Shinichi Tsukamoto

  DOI：10.1016/j.bmc.2003.12.032

  日期：2004.3

  A series of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for their bradycardic activities in isolated guinea pig right atria and in urethane-anesthetized rats. These efforts resulted in identification of the compound 8a, which exhibits potent bradycardic activity with minimal influence on mean blood pressure in urethane-anesthetized rats. Oral administration of compound 8a to conscious rats revealed increased potency and prolonged duration of action when compared to Zatebradine. (C) 2004 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of 2-(2-oxoethyl)pyrimidine-5-carboxamide derivatives as acetylcholinesterase inhibitors
  作者：Chuang Han、Ben-Ben Wei、Pan-Pan Shang、Xin-Yuan Guo、Li-Gai Bai、Zheng-Yue Ma

  DOI：10.1016/j.bmcl.2022.128873

  日期：2022.9

  A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer’s disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC50 = 0.88 ± 0.78 μM), which was better than that of Huperzine-A, and its inhibitory effect

  设计、合成和评估了一系列新的 2-(2-氧代乙基)嘧啶-5-甲酰胺衍生物作为治疗阿尔茨海默病 (AD) 的乙酰胆碱酯酶抑制剂 (AChEI)。生物活性结果表明，化合物10q对AChE的抑制活性最好（IC 50  = 0.88 ± 0.78 μM），优于石杉碱甲，对BuChE的抑制作用较弱（IC 50  = 10.0 ± 1.30 μM ） )，这表明化合物10q是主要的 AChE 抑制剂。此外，分子对接研究结果显示，10q可以同时与 AChE 的 CAS 和 PAS 位点结合，这与10q的酶动力学研究显示的混合抑制模式一致。此外，利用molinspiration server和pkCSM对目标化合物的分子性质进行了在线预测，结果表明化合物10q具有满足Lipinski五法则的类药物性质。基于生物活性和分子特性，进一步开发的化合物10q是有价值的。