N-nicotinoyl dopamine | 84454-97-7

• 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: N-nicotinoyl dopamine
• 英文别名: N-nicotinoyldopamine；NND；N-[2-(3,4-dihydroxyphenyl)ethyl]pyridine-3-carboxamide
• CAS: 84454-97-7
• 化学式: C₁₄H₁₄N₂O₃
• 分子量: 258.277
• InChiKey: UNFZEXBBGOCRBZ-UHFFFAOYSA-N

物化性质

• 熔点：
  159-162 °C(Solv: isopropanol (67-63-0))
• 沸点：
  590.9±45.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  82.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 N-nicotinoyl dopamine 以 氯仿 为溶剂， 反应 6.0h， 生成 3-carbamoyl>pyridine
  参考文献：
  名称：

  通过生物膜改善递送。13.多巴胺与二氢吡啶的脑特异性递送，与吡啶鎓盐型氧化还原递送系统平衡。

  摘要：

  与吡啶鎓盐型氧化还原递送系统平衡的二氢吡啶用于脑特异性递送多巴胺。体内施用邻苯二酚保护的多巴胺与1,4-二氢甘油三苯胺作为载体，导致大脑特异性，高浓度和持续浓度的1-甲基-3- [N-β-（3,4-二羟基苯基）多巴胺的直接前体乙基] [氨基甲酰基]吡啶鎓盐在大脑中锁定了多个小时，而全身浓度迅速下降，不到30分钟以1/2的速度下降。在大脑中观察到了明显的多巴胺能活性，持续了几个小时。

  DOI：

  10.1021/jm00358a013
• 作为产物：
  描述：

  烟酸 、 盐酸多巴胺 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 反应 12.0h， 生成 N-nicotinoyl dopamine
  参考文献：
  名称：

  N-Nicotinoyl dopamine inhibits skin pigmentation by suppressing of melanosome transfer

  摘要：

  We investigated the inhibitory effects of a niacinamide derivative, N-Nicotinoyl dopamine (NND) on melanogenesis. NND inhibits melanosome transfer in a normal human melanocyte-keratinocyte coculture system and through phagocytic ability without affecting viability of cells while it did not show inhibitory effects of tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. In addition, safety of NND was verified through performing neural stem cell morphology assay. Our findings indicate that NND may potentially be used for cosmetic industry for improvement of skin whitening and therapies related with several skin disorders, and the effect of NND may be acquired via reduction of melanosome transfer. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2015.11.025
• 作为试剂：
  描述：

  、 N-[2-(4-hydroxyphenyl)ethyl]-3-pyridinecarboxamide 、 三甲基乙酰氯 在 N-nicotinoyl dopamine 、 水 、 氯离子 、 solution 、 碳酸氢钠 、 氯仿 、 ether pet. ether 作用下， 以 氯仿 为溶剂， 反应 16.0h， 生成 3-{N-[β-(4-pivalyloxyphenyl)ethyl]}carbamoyl pyridine
  参考文献：
  名称：

  Brain-specific drug delivery

  摘要：

  中央作用药物种类通过给予需要此类治疗的患者一种治疗有效量的目标药物种类[D]，该药物种类被系于一种二氢吡啶类型的还原、穿过血脑屏障的脂质形式[D-DHC]上，以特定部位/持续方式送达到大脑。体内二氢吡啶载体基团的氧化形成离子型吡啶盐型药物/载体实体[D-QC]⁺，防止其从大脑中消除，而从一般循环中的消除则加速，随后四级载体/药物种类的断裂导致药物[D]在大脑中持续释放，载体基团[QC]⁺则容易被消除。

  公开号：

  US04479932A1

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。
• Synthesis of nicotinamide derivatives having a hydroxy-substituted benzene ring and the influence of their structures on the apoptosis-inducing activity against leukemia cells
  作者：Tomoko Yamaguchi、Yuriko Matsumura、Takuya Ishii、Yoshikazu Tokuoka、Keisuke Kurita

  DOI：10.1002/ddr.20426

  日期：2011.5

  With the view of developing novel apoptosis‐inducing agents against malignant cells, nicotinamide derivatives containing substituted O‐benzoyl‐tyrosine, dopamine, and norepinephrine residues were synthesized. Antiproliferative activity measurements using leukemia U937 cells revealed that the benzoyl‐tyrosine derivative having two hydroxys at C‐2 and C‐3 on the benzoyl group, and the one having a hydroxy

  为了开发针对恶性细胞的新型凋亡诱导剂，合成了包含取代的O-苯甲酰基酪氨酸，多巴胺和去甲肾上腺素残基的烟酰胺衍生物。使用白血病U937细胞进行的抗增殖活性测量表明，苯甲酰基酪氨酸衍生物在C-2和C-3的苯甲酰基上有两个羟基，而在C-2羟基和C-4上有甲氧基的那个被证明是最多的。在9种烟酰胺衍生物中有效。IC 50这些化合物的值分别为0.87和3.15 µM，表明它们与表没食子儿茶素没食子酸酯相比具有显着的活性，没食子儿茶素没食子酸酯是绿茶中的儿茶素成分，以其显着的活性而闻名。琼脂糖凝胶电泳和染料染色证实细胞死亡过程是细胞凋亡的结果，表明这些化合物作为诱导细胞凋亡的抗癌剂具有很高的潜力。Drug Dev Res 72：289–297，2011.©2010 Wiley-Liss，Inc.
• Redox systems for brain-targeted drug delivery
  申请人：University of Florida

  公开号：US05017566A1

  公开（公告）日：1991-05-21

  Inclusion complexes of hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of .beta.- and .gamma.-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 redox 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、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。
• 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.-。