1-methyl-3-{N-[[β-[3,4-bis(isobutyryloxy)phenyl]ethyl]]}carbamoylpyridinium trifluoroacetate | 118453-76-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 1-methyl-3-{N-[[β-[3,4-bis(isobutyryloxy)phenyl]ethyl]]}carbamoylpyridinium trifluoroacetate
• 英文别名: 1-methyl-3-{N-[[beta-[3,4-bis(isobutyryloxy)phenyl]ethyl]]carbamoyl}-pyridinium trifluoroacetate；[2-(2-methylpropanoyloxy)-4-[2-[(1-methylpyridin-1-ium-3-carbonyl)amino]ethyl]phenyl] 2-methylpropanoate;2,2,2-trifluoroacetate
• CAS: 118453-76-2
• 化学式: C₂F₃O₂*C₂₃H₂₉N₂O₅
• 分子量: 526.51
• InChiKey: GOGOVVARJAWFOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-methyl-3-{N-[[β-[3,4-bis(isobutyryloxy)phenyl]ethyl]]}carbamoylpyridinium trifluoroacetate 生成 1-methyl-3-{N-[[β-[3,4-bis(isobutyryloxy)phenyl]ethyl]]}carbamoyl-1,4-dihydropyridine
  参考文献：
  名称：

  BODOR, NICHOLAS S.

  摘要：

  DOI：
• 作为产物：
  描述：

  1-methyl-3-carbamoyl>pyridinium iodide 以 trifluoroacetic acid, isobutyryl chloride 为溶剂， 以1.2 g (30.4%)的产率得到1-methyl-3-{N-[[β-[3,4-bis(isobutyryloxy)phenyl]ethyl]]}carbamoylpyridinium trifluoroacetate
  参考文献：
  名称：

  Redox systems for brain-targeted drug delivery

  摘要：

  羟丙基、羟乙基、葡萄糖基、麦芽糖基和麦芽三糖基衍生物与β-和γ-环糊精的包含复合物，与还原的、可生物氧化的、能穿透血脑屏障的、脂质形式的二氢吡啶.反应.pyridinium盐氧化还原系统形成脑靶向药物输送的一种手段，用于稳定氧化还原系统，特别是对抗氧化作用。氧化还原包含复合物还提供了一种减少系统给药后肺部初始药物浓度的手段，从而降低毒性。在某些情况下，复合作用显著提高了氧化还原系统的水溶性。

  公开号：

  US05017566A1

文献信息

• Pharmaceutical formulations for parenteral use
  申请人：University of Florida

  公开号：US04983586A1

  公开（公告）日：1991-01-08

  Aqueous parenteral solutions of drugs which are insoluble or only sparingly soluble in water and/or which are unstable in water, combined with hydroxypropyl-.beta.-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.

  将不溶或在水中仅微溶或在水中不稳定的药物与羟丙基-β-环糊精结合，提供了一种缓解与药物在注射部位沉淀以及/或在注射后在肺部或其他器官中沉淀相关问题的方法。
• 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.-。
• Brain-specific dopaminergic activity involving dihydropyridine
  申请人：University of Florida

  公开号：US04727079A1

  公开（公告）日：1988-02-23

  A brain-specific dopaminergic response is elicited in a patient in need of such treatment, e.g., a patient afflicted with Parkinson's disease of hyperprolactinemia, by administering thereto a therapeutically effective amount of preferably catechol protected dopamine tethered to a reduced, blood-brain barrier penetrating lipoidal form [D-DHC] of a dihydropyridine.revreaction.pyridinium salt type redox carrier, e.g., 1,4-dihydrotrigonelline. Oxidation of the dihydropyridine carrier moiety in vivo to the ionic pyridinium salt type dopamine/carrier entity [D-QC].sup.+ prevents elimination thereof from the brain, while elimination from the general circulation is accelerated, resulting in significant and prolongedly sustained brain-specific dopaminergic activity.

  一种特定于大脑的多巴胺反应被引发，以治疗有需要的患者，例如，患有帕金森病或垂体高泌乳素血症的患者，通过向其投予一定量的治疗有效的優選的優選的優選的優選的優選的多巴胺，其被连接到一种降低的，穿透血脑屏障的脂质形式[D-DHC]的二氢吡啶盐型氧化还原载体，例如，1,4-二氢三甲基咖啡碱。体内二氢吡啶载体基团的氧化形成离子型吡啶盐型多巴胺/载体实体[D-QC].sup.+，防止其从大脑中排泄，同时加速其从一般循环中的排泄，导致显著且持续时间较长的大脑特异性多巴胺活性。
• Brain-specific drug delivery of steroid sex hormones cleaved from
  申请人：University of Florida

  公开号：US04900837A1

  公开（公告）日：1990-02-13

  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.

  这些化合物适用于特定部位/持续性地将中枢神经系统药物物种传递到大脑，其中包括：（a）公式[D--DHC]（I）的化合物，其中[D]是中枢神经系统药物物种，[DHC]是二氢吡啶盐氧化还原载体的还原、可生物氧化、穿过血脑屏障的脂质形式，但当[DHC]为##STR1##其中R为低级烷基或苄基，[D]为含有单个NH.sub.2或OH官能团的药物物种，当存在单个OH官能团时，其为一级或二级OH官能团，该药物物种通过NH.sub.2或OH功能团直接连接到[DHC]的羰基功能团，则[D]必须不是交感神经兴奋剂、类固醇性激素或长链烷醇；以及（b）公式（I）的化合物的非毒性药用可接受盐，其中[D]是中枢神经系统药物物种，[DHC]是二氢吡啶盐氧化还原载体的还原、可生物氧化、穿过血脑屏障的脂质形式。还公开了相应的离子吡啶盐型药物/载体[D--QC].sup.+ X.sup.-。
• Improvements in redox systems for brain-targeted drug delivery
  申请人：University of Florida

  公开号：US05002935A1

  公开（公告）日：1991-03-26

  Inclusion complexes of hydroxypropyl-.beta.-cyclodextrin with the reduced biooxidizable, blood-brain barrier penetrating, lipoidal forms of dihydropyridine.revreaction.pyridinium salt redox systems for brain-targeted drug delivery provide a means for stabilizing the redox systems, particularly against oxidation. The reodox inclusion complexes also provide a means for decreasing initial drug concentrations in the lungs after administration of the systems, leading to decreased toxicity. In selected instances, complexation results in substantially improved water solubility of the redox systems as well.

  羟丙基-β-环糊精与可还原、可氧化的穿过血脑屏障的脂质型二氢吡啶盐氧化还原系统形成的包合物，可用于脑靶向药物传递，提供了一种稳定氧化还原系统的手段，特别是对抗氧化反应。包合物还可用于降低系统给药后肺部初始药物浓度，从而降低毒性。在某些情况下，包合物也可显著提高氧化还原系统的水溶性。