meso-Inosit-hexanicotinat | 497820-05-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: meso-Inosit-hexanicotinat
• 英文别名: Mesoinositol-nicotinat；Mesonex；1,2,3,4,5,6-hexakis-nicotinoyloxy-cyclohexane；inositol hexanicotinate；Inositol niacinate；[2,3,4,5,6-pentakis(pyridine-3-carbonyloxy)cyclohexyl] pyridine-3-carboxylate
• CAS: 497820-05-0
• 化学式: C₄₂H₃₀N₆O₁₂
• 分子量: 810.733
• InChiKey: MFZCIDXOLLEMOO-UHFFFAOYSA-N

物化性质

• 溶解度：
  Insoluble

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  60
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  235
• 氢给体数：
  0
• 氢受体数：
  18

ADMET

代谢

肌醇烟酸酯通过血浆酯酶的水解作用，以持续的方式释放出游离的烟酸和肌醇。这个过程需要超过48小时，其中发现肌醇六烟酸酯的血浆酶水解在肌醇六烟酸酯的第一个酯键比后续的键慢。肌醇烟酸酯的逐步水解每一步形成一个烟酸分子，最终产生六个烟酸分子和一个肌醇部分。

Inositol nicotinate undergoes hydrolysis by plasma esterases, releasing free nicotinic acid and inositol in a sustained manner. The process takes more than 48hours, where the bloodstream enzymatic hydrolysis of inositol hexanicotinate was found to be slower in the first ester linkage of inositol hexanicotinate than in subsequent linkages. Sequential hydrolytic steps of inositol nicotinate forms one nicotinic acid molecule in each step, producing eventually six molecules of nicotinic acid and one inositol moiety.

来源:DrugBank

吸收、分配和排泄

• 吸收

肌醇六烟酸酯的胃肠道吸收差异很大，平均而言，口服剂量的70%从胃和上段小肠以完整形式吸收进入血液。服用后，烟酸的最大血药浓度在大约6-10小时后达到。在低浓度时，烟酸和烟酰胺的吸收是通过钠离子依赖的促进扩散介导的。在高浓度时，被动扩散占主导，3到4克烟酸的剂量几乎被完全吸收。

Gastrointestinal absorption of inositol hexanicotinate varies widely, with an average of 70% of an orally ingested dose absorbed from stomach and upper small intestines into the bloodstream as intact form. The maximum serum levels of nicotinic acid is reached approximately 6-10 hours after oral ingestion. At low concentrations, the absorption of nicotinic acid and nicotinamide is mediated by sodium ion-dependent facilitated diffusion. At higher concentrations, passive diffusion predominates with doses of 3 to 4 g of niacin being almost completely absorbed.

来源:DrugBank

吸收、分配和排泄

• 消除途径

未吸收的烟酸肌醇在粪便中被检测到。

Unabsorbed inositol nicotinate is detected in feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

静脉注射50mg/kg肌醇烟酸酯后，大鼠的平均分布体积为1051±250 mL/kg。

Mean Vd following intravenous administration of 50mg/kg of inositol nicotinate in rats is 1051±250 mL/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

在大鼠中，静脉注射50mg/kg肌醇烟酸后的平均清除率为65.4±19 mL/min/kg。

Mean clearance rate following intravenous administration of 50mg/kg of inositol nicotinate in rats is 65.4±19 mL/min/kg.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  meso-Inosit-hexanicotinat 、 碘甲烷 生成 [2,3,4,5,6-pentakis[(1-methylpyridin-1-ium-3-carbonyl)oxy]cyclohexyl] 1-methylpyridin-1-ium-3-carboxylate;hexaiodide
  参考文献：
  名称：

  STACPOOLE, PETER W.;BODOR, NICHOLAS S.

  摘要：

  DOI：
• 作为产物：
  描述：

  烟酸 、 1L-手性纤维醇 、 三氯氧磷 生成 meso-Inosit-hexanicotinat
  参考文献：
  名称：

  STACPOOLE, PETER W.;BODOR, NICHOLAS S.

  摘要：

  DOI：

文献信息

• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• GLUTATHIONE-CHOLESTEROL DERIVATIVES AS BRAIN TARGETING AGENTS
  申请人：South Dakota Board of Regents

  公开号：US20200048305A1

  公开（公告）日：2020-02-13

  The present invention describes compositions containing cholesterol-linker-glutathione conjugates for targeting the brain by overcoming barrier entry to the CNS through the blood brain barrier (BBB), including micelle and liposome forms of such compositions. In addition, methods for treating subjects by administering such compositions are also disclosed.

  本发明描述了含有胆固醇-连接剂-谷胱甘肽共轭物的组合物，通过克服血脑屏障（BBB）进入中枢神经系统的屏障入口，包括这些组合物的胶束和脂质体形式。此外，还公开了通过给予这些组合物治疗受试者的方法。
• SUBSTITUTED AMIDE COMPOUNDS
  申请人：Pfizer Inc.

  公开号：US20140315928A1

  公开（公告）日：2014-10-23

  The present invention is directed at substituted amide compounds, pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

  本发明涉及替代酰胺化合物，含有这种化合物的药物组合物以及利用这种化合物降低血浆脂质水平，如LDL-胆固醇和甘油三酯，并据此治疗由高水平的LDL-胆固醇和甘油三酯加重的疾病，如动脉粥样硬化和心血管疾病，在哺乳动物，包括人类中的应用。
• Tyrosine kinase inhibitors
  申请人：——

  公开号：US20020137755A1

  公开（公告）日：2002-09-26

  The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

  本发明涉及抑制、调节和/或调控酪氨酸激酶信号传导的化合物，含有这些化合物的组合物，以及使用它们治疗依赖于酪氨酸激酶的疾病和病况的方法，如在哺乳动物中的血管生成、癌症、肿瘤生长、动脉粥样硬化、老年性黄斑变性、糖尿病视网膜病变、炎症性疾病等。
• 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。