5-(N-methyl-N-propargylaminomethyl)quinolin-8-yl ethylmethylcarbamate | 1229212-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-(N-methyl-N-propargylaminomethyl)quinolin-8-yl ethylmethylcarbamate
• 英文别名: 5-((methyl(propargyl)amino)methyl)quinolin-8-yl ethyl(methyl)carbamate；Prochelators, 3；[5-[[methyl(prop-2-ynyl)amino]methyl]quinolin-8-yl] N-ethyl-N-methylcarbamate
• CAS: 1229212-79-6
• 化学式: C₁₈H₂₁N₃O₂
• 分子量: 311.384
• InChiKey: PUJNUVGKNFPWML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-乙基甲基胺 、 生成 5-(N-methyl-N-propargylaminomethyl)quinolin-8-yl ethylmethylcarbamate
  参考文献：
  名称：

  Site-Activated Chelators Targeting Acetylcholinesterase and Monoamine Oxidase for Alzheimer’s Therapy

  摘要：

  Chelators have the potential to treat the underlying cause of Alzheimer's disease (AD), but their therapeutic use is hampered by their poor targeting and poor permeability to the brain and/or toxic effects. Here, we report a new strategy for designing site-activated chelators targeting both acetylcholinesterase (AChE) and monoamine oxidase (MAO). We demonstrated that our lead 2 inhibited both AChE and MAO in vitro, but with little affinity for metal (Fe, Cu, and Zn) ions. Compound 2 can be activated by inhibition of AChE to release an active chelator M30. M30 has been shown to be able to modulate amyloid precursor protein regulation and beta-amyloid reduction, suppress oxidative stress, and passivate excess metal ions (Fe, Cu, and Zn). Compound 2 was less cytotoxic and more lipophilic than the brain-permeable chelator M30. Our new strategy is relatively simple and generally produces small and simple molecules with drug-like properties; it thus holds a potential use in designing site-activated multifunctional chelators with safer and more efficacious properties for treating other metal-related diseases such as Parkinson's disease and cancer where specific elimination of metals in cancer cells is required.

  DOI：

  10.1021/cb900264w

文献信息

• NEUROPROTECTIVE MULTIFUNCTIONAL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  申请人：Youdim Moussa B. H.

  公开号：US20120040993A1

  公开（公告）日：2012-02-16

  Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and/or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and/or treated by iron chelation therapy, and/or neuroprotection and/or neurorestoration, and/or apoptosis inhibition and/or MAO inhibition and/or cholinesterase inhibition and/or NMADR inhibition. The present invention encompasses compounds of the formulas I to VI.

  提供了多功能化合物，包括从以下选择的两个或多个官能团：(i)赋予铁螯合剂功能的官能团；(ii)赋予神经保护功能的官能团；(iii)赋予联合抗凋亡、神经保护和/或神经修复功能的官能团；(iv)赋予大脑MAO抑制作用的官能团，优选在肝脏和小肠中几乎没有或没有MAO抑制作用；(v)赋予胆碱酯酶抑制作用的官能团；(vi)赋予N-甲基-D-天门冬氨酸受体(NMDAR)抑制作用的官能团，以及其药学上可接受的盐和光学异构体。这些多功能化合物在预防和/或治疗可以通过铁螯合疗法、神经保护和/或神经修复、凋亡抑制和/或MAO抑制和/或胆碱酯酶抑制和/或NMDAR抑制来预防和/或治疗的疾病、疾病或状况中是有用的。本发明涵盖了公式I至VI的化合物。
• US8802675B2
  申请人：——

  公开号：US8802675B2

  公开（公告）日：2014-08-12
• [EN] NEUROPROTECTIVE MULTIFUNCTIONAL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM<br/>[FR] COMPOSÉS MULTIFONCTIONNELS NEUROPROTECTEURS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：YEDA RES & DEV

  公开号：WO2010086860A2

  公开（公告）日：2010-08-05

  Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and/or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and/or treated by iron chelation therapy, and/or neuroprotection and/or neurorestoration, and/or apoptosis inhibition and/or MAO inhibition and/or cholinesterase inhibition and/or NMADR inhibition. The present invention encompasses compounds of the formulas I to Vl.