β-apo-8'-carotenoic acid | 1962-15-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: β-apo-8'-carotenoic acid
• 英文别名: Apo-8'-carotenoic Acid；(2E,4E,6E,8E,10E,12E,14E,16E)-2,6,11,15-tetramethyl-17-(2,6,6-trimethylcyclohexen-1-yl)heptadeca-2,4,6,8,10,12,14,16-octaenoic acid
• CAS: 1962-15-8
• 化学式: C₃₀H₄₀O₂
• 分子量: 432.646
• InChiKey: MREKHRDVEZGVPJ-CUIXVSHYSA-N

物化性质

• 熔点：
  189-191 °C
• 沸点：
  609.8±24.0 °C(Predicted)
• 密度：
  0.991±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  β-apo-8'-carotenoic acid 在 4-二甲氨基吡啶 、 氢溴酸 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 75.0h， 生成 2-(N,N-di(2-hydroxyethyl)amino)ethyl-β-apo-8‘-carotenoate hydrobromide
  参考文献：
  名称：

  [EN] NOVEL CATIONIC CAROTENOID-BASED LIPIDS FOR CELLULAR NUCLEIC ACID UPTAKE
  [FR] NOUVEAUX LIPIDES CATIONIQUES À BASE DE CAROTÉNOÏDE POUR LA CAPTURE CELLULAIRE D'ACIDE NUCLÉIQUE

  摘要：

  公开号：

  WO2014071072A3
• 作为产物：
  描述：

  (2E,4E,6E,8E,10E,12E,14E,16E)-2,6,11,15-四甲基-17-(2,6,6-三甲基-1-环己烯-1-基)-2,4,6,8,10,12,14,16-十七碳八烯酸乙酯 在 水 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 为溶剂， 以69%的产率得到β-apo-8'-carotenoic acid
  参考文献：
  名称：

  天然类胡萝卜素及其合成糖肽结合物抑制 SARS-CoV-2 复制

  摘要：

  旷日持久的全球 COVID-19 大流行促使开发针对病原体 SARS-CoV-2 的新药。临床上使用的糖肽类抗生素替考拉宁成为一种潜在的抗病毒药物，并且通过亲脂性修饰提高了其疗效。这促使我们制备替考拉宁、其假糖苷配基和相关瑞斯托霉素糖苷配基的新型亲脂性类胡萝卜素缀合物。使用细胞活力测定和病毒 RNA 的定量 PCR 在 Vero E6 细胞中测试了它们对 SARS-CoV-2 的抗病毒作用，证实了它们对病毒复制的微摩尔抑制活性。有趣的是，母体类胡萝卜素中的两种，bixin 和 β-apo-8'胡萝卜素酸，发挥了显着的抗 SARS-CoV-2 活性。机制研究涉及组织蛋白酶 L 和 B，以及主要蛋白酶 3CLPro，并且通过计算研究使结果合理化。糖肽缀合物显示双重抑制作用，而类胡萝卜素主要具有组织蛋白酶 B 和 L 亲和力。由于替考拉宁是一种上市抗生素，而天然碧玺是一种经批准、廉价且广泛使用的

  DOI：

  10.3390/ph14111111

文献信息

• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Novel Cationic Carotenoid Lipids as Delivery Vectors of Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy
  作者：Linda J. Popplewell、Aseel Abu-Dayya、Tushar Khanna、Marcella Flinterman、Nada Abdul Khalique、Liji Raju、Christer L. Øpstad、Hans-Richard Sliwka、Vassilia Partali、George Dickson、Michael D. Pungente

  DOI：10.3390/molecules17021138

  日期：——

  Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

  杜氏肌营养不良症(Duchenne Muscular Dystrophy, DMD)是一种常见、遗传性且无法治愈的致命肌肉萎缩疾病,由破坏DMD基因阅读框架的缺失引起,导致无法产生功能性dystrophin蛋白。反义寡核苷酸(antisense oligonucleotide, AO)介导的剪接位点跳跃可以恢复DMD基因的阅读框架,并表达截短但具有功能的dystrophin蛋白。本研究的目的是评估两种新型刚性阳离子类胡萝卜素脂质C30-20和C20-20在正常人骨骼肌原代细胞(human skeletal muscle primary cells, hSkMCs)中递送针对DMD mRNA外显子45跳跃设计的磷酸二酰胺吗啉(phosphorodiamidate morpholino, PMO)AO的效率。阳离子类胡萝卜素脂质/PMO-AO脂质体复合物相对于已知的商业脂质1,2-二肉豆蔻酰-sn-甘油-3-乙基磷酰胆碱(1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine, EPC)显著提高了外显子45的跳跃效率。
• Glucuronidated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014734A1

  公开（公告）日：2007-01-18

  This invention provides glucuronidated nebivolol metabolites and pharmaceutical compositions of glucuronidated nebivolol metabolites for treatment of cardiovascular diseases. In addition, this invention also provides compositions comprising nebivolol and/or at least one glucuronidated metabolite of nebivolol and/or at least one other active compound in a pharmaceutically acceptable carrier. This invention also provides methods of treating and/or preventing vascular diseases, by administering at least one glucuronidated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one glucuronidated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  这项发明提供了葡萄糖醛酸化的尼布ivolol代谢物以及用于治疗心血管疾病的葡萄糖醛酸化的尼布ivolol代谢物的制药组合物。此外，该发明还提供了包含尼布ivolol和/或至少一种尼布ivolol的葡萄糖醛酸化代谢物和/或至少一种其他活性化合物的药用可接受载体的组合物。该发明还提供了通过向受影响血管疾病的靶位点投与至少一种能释放治疗有效量一氧化氮的尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防血管疾病的方法。此外，该发明旨在通过投与至少一种尼布ivolol的葡萄糖醛酸化代谢物来治疗和/或预防偏头痛。该发明还可与代谢综合征紊乱的单一治疗或联合治疗一起使用。
• HYDROXYLATED NEBIVOLOL METABOLITES
  申请人：O'Donnell John P.

  公开号：US20110065783A1

  公开（公告）日：2011-03-17

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化的内比洛尔代谢物在急性给药后以浓度依赖的方式增加人类内皮细胞制备的一氧化氮释放。此外，羟基化的内比洛尔代谢物，包括但不限于4-羟基-6,6′-二氟-、4-羟基-5-酚-6,6′-二氟-和4-羟基-8-苯基-6,6′-二氟-，具有在慢性给药后增加人类内皮细胞释放一氧化氮能力的能力。本发明提供了羟基化的内比洛尔代谢物和包含内比洛尔和/或至少一种内比洛尔羟基化代谢物和/或至少一种用于治疗心血管疾病的其他化合物或其药学上可接受的盐的组合物。此外，本发明提供了通过给靶向受影响的血管疾病的部位至少给予一种能够释放治疗有效量一氧化氮的内比洛尔羟基化代谢物的方法来治疗和/或预防血管疾病的方法。此外，本发明还涉及通过至少给予一种内比洛尔羟基化代谢物来治疗和/或预防偏头痛。此发明还可与代谢综合征疾病的单个治疗或联合治疗一起使用。
• Compositions comprising nebivolol
  申请人：MYLAN LABORATORIES, INC

  公开号：EP2808015A1

  公开（公告）日：2014-12-03

  The active ingredients of the pharmaceutical composition described consist of nebivolol, one or more ACE inhibitors and one or more ARB.

  所述药物组合物的活性成分包括奈必洛尔、一种或多种 ACE 抑制剂和一种或多种 ARB。