1-methyl-3-{N-[2-(3-indolyl)ethyl]carbamoyl}-1,4-dihydropyridine | 59547-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-methyl-3-{N-[2-(3-indolyl)ethyl]carbamoyl}-1,4-dihydropyridine
• 英文别名: T-CDS；1-Methyl-3-{N-[2-(3-indolyl)ethyl]}carbamoyl-1,4-dihydropyridine；1-methyl-3-N-[2-(3-indolyl)ethyl]carbamoyl-1,4-dihydropyridine；N-[2-(1H-indol-3-yl)ethyl]-1-methyl-4H-pyridine-3-carboxamide
• CAS: 59547-45-4
• 化学式: C₁₇H₁₉N₃O
• 分子量: 281.357
• InChiKey: JDGMVFJOFGOWAS-UHFFFAOYSA-N

物化性质

• 熔点：
  40-70 °C
• 沸点：
  565.4±50.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  48.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  氯化烟碱盐酸盐 在 sodium dithionite 、 碳酸氢钠 作用下， 以 吡啶 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 反应 6.0h， 生成 1-methyl-3-{N-[2-(3-indolyl)ethyl]carbamoyl}-1,4-dihydropyridine
  参考文献：
  名称：

  A tryptamine analog with high affinity to the heart tissues is a potential antiarrhythmic agent

  摘要：

  摘要：合成了一种新的色胺类似物，1-甲基-3-[N-(3-吲哚基)乙基]氨基甲酰-1,4-二氢吡啶（T-CDS），并将其转化为与2-羟基丙基-β-环糊精形成稳定的固体复合物。将该复合物的水溶液静脉注射给狗，并在50分钟内监测血液中T-CDS及其对应的季铵（T-Q+）形式的浓度。在整个研究过程中监测药物对关键心脏参数的影响。实验结束时，狗被牺牲，并在不同心脏组织以及肾脏、肝脏、肺脏、大脑、尿液和脑脊液中确定了四级吡啶形式（T-Q+）的浓度。发现该化合物选择性地结合到心肌上，并在不同的心脏组织中显示出不同的浓度。在给予二氢吡啶形式（T-CDS）后，心脏中T-Q+的浓度要比直接给予T-Q+后高得多。该化合物对心血管系统的某些关键指标具有活性，可能是一种有效且安全的抗心律失常药物。

  DOI：

  10.1211/0022357011776054

文献信息

• Brain-specific drug delivery
  申请人：University of Florida

  公开号：US04824850A1

  公开（公告）日：1989-04-25

  The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are: (a) compounds of the formula [D--DHC] (I) wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine.revreaction.pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.2 or OH function group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and (b) non-toxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine.revreaction.pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entitles [D--QC].sup.+ X.sup.- are also disclosed.

  这些适用于将中枢作用药物种类定向/持续释放到大脑的主体化合物是：(a) 公式[D--DHC] (I)的化合物，其中[D]是中枢作用药物种类，[DHC]是二氢吡啶盐氧化还原、穿透血脑屏障的脂质形式，带有二氢吡啶盐氧化还原载体，但当[DHC]是##STR1##其中R是较低的烷基或苄基，[D]是含有单个NH.sub.2或OH官能团的药物种类，当存在单个OH官能团时，该OH官能团为一次或二次OH官能团，该药物种类通过NH.sub.2或OH官能团直接连接到[DHC]的羰基官能团，则[D]不能是交感神经刺激剂、类固醇性激素或长链烷醇；以及(b) 公式(I)的化合物的无毒的药用可接受盐，其中[D]是中枢作用药物种类，[DHC]是二氢吡啶盐氧化还原、穿透血脑屏障的脂质形式，带有二氢吡啶盐氧化还原载体。还披露了相应的离子式吡啶盐型药物/载体[D--QC].sup.+ X.sup.-。
• Pharmaceutical formulations for parenteral use
  申请人：UNIVERSITY OF FLORIDA

  公开号：EP0335545A2

  公开（公告）日：1989-10-04

  Aqueous parenteral solutions of drugs which are insoluble or only sparingly'soluble in water and/or which are unstable in water, combined with a hydroxypropyl,hydroxyethyl, glucosyl, maltosyl or maltotriosyl derivative of 3-or γ-cyclodextrin, provide a means for alleviating problems associated with drug precipitation at the injection site and/or in the lungs or other organs following parenteral administration.

  不溶于水或只能少量溶于水和/或在水中不稳定的药物的肠外水溶液与 3-或 γ-环糊精的羟丙基、羟乙基、葡糖基、麦芽糖基或麦芽三糖基衍生物结合使用，可以缓解肠外给药后药物在注射部位和/或肺部或其他器官沉淀的问题。
• Cyclodextrin complexation
  申请人：CYCLOPS h.f.

  公开号：EP0579435A1

  公开（公告）日：1994-01-19

  The invention provides a method for enhancing the complexation of a cyclodextrin with a lipophilic and/or water-labile drug, comprising combining from about 0.1 to about 70% (weight/volume) of a cyclodextrin and from about 0.001 to about 5% (weight/volume) of a pharmaceutically acceptable, pharmacologically inactive, water-soluble polymer in an aqueous medium, the polymer and cyclodextrin being dissolved in the aqueous medium before the drug is added, the aqueous medium which comprises the polymer and cyclodextrin being maintained at from about 30 to about 150°C for a period of from about 0.1 to about 100 hours before, during and/or after the drug is added, optionally followed by removal of water. Related methods, co-complexes of drug/cyclodextrin/polymer, pharmaceutical compositions and cyclodextrin/polymer complexing agents are also provided. Analogous methods, co-complexes and compositions in which the drug is replaced with a food additive, cosmetic additive or agrochemical are also described.

  本发明提供了一种增强环糊精与亲脂性和/或水溶性药物复配的方法，包括将约 0.1%至约 70%（重量/体积）的环糊精和约 0.001至约5%（重量/体积）的药学上可接受的、药理上无活性的水溶性聚合物在水介质中，聚合物和环糊精在添加药物之前溶解在水介质中，包含聚合物和环糊精的水介质在添加药物之前、期间和/或之后在约30至约150°C的温度下保持约0.1至约100小时，可选地随后除去水。还提供了相关的方法、药物/环糊精/聚合物的共复合物、药物组合物和环糊精/聚合物复配剂。此外，还介绍了用食品添加剂、化妆品添加剂或农用化学品替代药物的类似方法、共混物和组合物。
• BODOR, NICHOLAS S.
  作者：BODOR, NICHOLAS S.

  DOI：——

  日期：——
• BRAIN-SPECIFIC DRUG DELIVERY
  申请人：UNIVERSITY OF FLORIDA

  公开号：EP0110955A1

  公开（公告）日：1984-06-20