3,5-dipentadecyloxybenzenecarboxamidine hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,5-dipentadecyloxybenzenecarboxamidine hydrochloride
• 英文别名: 3,5-dipentadecyloxybenzamidine hydrochloride；TRX-20；3,5-dipentacyloxybenzamidine hydrochloride；3,5-di(pentadecoxy)benzenecarboximidamide;hydrochloride
• 化学式: C₃₇H₆₈N₂O₂*ClH
• 分子量: 609.42
• InChiKey: IWOPYKUVKWBHOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.33
• 重原子数：
  42
• 可旋转键数：
  31
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  68.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  溴代十五烷 在 盐酸 、 氨 、 potassium carbonate 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3,5-dipentadecyloxybenzenecarboxamidine hydrochloride
  参考文献：
  名称：

  Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

  摘要：

  Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios - 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP)-of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-a from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.

  DOI：

  10.2147/ijn.s141095

文献信息

• LIPOSOMES
  申请人：TERUMO KABUSHIKI KAISHA

  公开号：EP1044679A1

  公开（公告）日：2000-10-18

  This invention provides a liposome having a drug included therein, which has active targeting property and ensured stability in blood and can be used effectively in the diagnosis and/or treatment of diseases, particularly renal diseases, that accompany production of proteoglycan, comprising (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 1 to 20 mol% of (1) based on (3) and from 0.2 to 5 mol% of (2) based on the total of (1) and (3).

  本发明提供了一种含有药物的脂质体，该脂质体具有活性靶向性，并确保在血液中的稳定性，可有效用于诊断和/或治疗伴随蛋白多糖产生的疾病，特别是肾脏疾病、包括(1)在生理 pH 值范围内带正电荷的碱性化合物，(2)亲水性聚合物的脂质衍生物和(3)构成脂质体的脂质，作为其膜构成成分，其中它们的构成比例为(1)占(3)的 1 至 20 摩尔%，(2)占(3)的 0.2至5 摩尔%的(2)，以(1)和(3)的总和为基准。
• LIPOSOME PREPARATION CONTAINING SLIGHTLY WATER-SOLUBLE CAMPTOTHECIN
  申请人：TERUMO KABUSHIKI KAISHA

  公开号：EP1759699A1

  公开（公告）日：2007-03-07

  The present invention aims at providing a slightly water-soluble camptothecin liposome preparation with an excellent retention in blood for a drug, which can stably hold a slightly water-soluble camptothecin compound for a long period of time, whereby hydrolysis of an α-hydroxylactone ring in blood is suppressed and the slightly water-soluble camptothecin compound is kept in a structure in which the ring is not opened and which makes the compound effective as an antitumor-active drug, and, moreover, the liability of the drug to leave a liposome is advantageously reduced, so that it is possible to maintain the drug concentration in plasma for a long period of time after administration. This object is achieved by the liposome preparation as described in the specification. The liposome preparation according to the present invention includes a liposome preparation including as lipid components for forming a membrane a phospholipid and a fatty acid, and containing as a drug a lightly water-soluble camptothecin compound.

  本发明旨在提供一种在血液中对药物具有良好保留作用的微水溶性喜树碱脂质体制剂，该制剂可长期稳定地保留微水溶性喜树碱化合物、其中，α-羟基内酯环在血液中的水解被抑制，微水溶性喜树碱化合物被保持在环不被打开的结构中，从而使该化合物作为抗肿瘤活性药物有效，此外，药物离开脂质体的可能性被有利地降低，因此，在给药后，血浆中的药物浓度可以保持很长一段时间。本说明书所述的脂质体制剂可实现这一目标。根据本发明的脂质体制剂包括一种脂质体制剂，其中包括作为形成膜的脂质成分的磷脂和脂肪酸，并含有作为药物的轻水溶性喜树碱化合物。
• IRINOTECAN PREPARATION
  申请人：TERUMO KABUSHIKI KAISHA

  公开号：EP1752150A1

  公开（公告）日：2007-02-14

  Provided is an irinotecan formulation capable of supporting irinotecan and/or a salt thereof in a closed vesicle carrier at a high concentration and existing in blood for a long period of time by dramatically improved retentivity in blood compared to a conventionally known irinotecan liposome formulation. That is, an irinotecan formulation including a closed vesicle formed by a lipid membrane, in which irinotecan and/or a salt thereof is encapsulated at a concentration of at least 0.07 mol/mol (drug mol/membrane total lipid mol). There is an ion gradient between an inner aqueous phase and an outer aqueous phase in the irinotecan formulation. The closed vesicle is preferably liposome, in which only the outer surface of the liposome is preferably modified with a surface-modifying agent containing a hydrophilic polymer.

  本发明提供了一种伊立替康制剂，与传统已知的伊立替康脂质体制剂相比，该制剂能够在封闭的囊泡载体中以高浓度支持伊立替康和/或其盐，并通过显著提高在血液中的滞留性而长期存在于血液中。也就是说，伊立替康制剂包括由脂质膜形成的封闭囊泡，其中封装的伊立替康和/或其盐的浓度至少为 0.07 摩尔/摩尔（药物摩尔/膜总脂质摩尔）。在伊立替康制剂中，内水相和外水相之间存在离子梯度。封闭的囊泡最好是脂质体，其中只有脂质体的外表面最好用含有亲水性聚合物的表面修饰剂进行修饰。
• AMPHIPHILIC COMPOUND, AND RESIN COMPOSITION FOR MEDICAL USE AND DRUG ADDITIVE EACH USING SAME
  申请人：Nippon Shokubai Co., Ltd.

  公开号：EP3950735A1

  公开（公告）日：2022-02-09

  Provided is means capable of reducing the adsorptivity to plastics while suppressing a decrease in intracellular uptake efficiency in an amphiphilic compound that can be applied to long-term blood-retaining liposomes or the like as a drug carrier. The above problem can be solved by an amphiphilic compound comprising a moiety (I) including a constitutional unit (A) derived from a monomer (a) having two or more hydroxyl groups and having 2 to 10 carbon atoms constituting the side chain among the carbon atoms of the constitutional unit, and a hydrocarbon group having 8 or more carbon atoms.

  本发明提供了一种方法，能够降低两亲化合物对塑料的吸附性，同时抑制细胞内吸收效率的降低，这种两亲化合物可用作长期留血脂质体或类似药物载体。 上述问题可以通过一种两亲化合物来解决，该化合物包含一个分子（I），该分子（I）包括一个由单体（a）衍生的构型单元（A），该单体（a）具有两个或两个以上羟基，在构型单元的碳原子中具有 2 至 10 个碳原子构成侧链，以及一个具有 8 个或 8 个以上碳原子的烃基。
• Liposome
  申请人：Terumo Kabushiki Kaisha

  公开号：US20030211142A1

  公开（公告）日：2003-11-13

  This invention provides a liposome having a drug included therein, which has active targeting property and ensured stability in blood and can be used effectively in the diagnosis and/or treatment of diseases, particularly renal diseases, that accompany production of proteoglycan, comprising (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 1 to 20 mol % of (1) based on (3) and from 0.2 to 5 mol % of (2) based on the total of (1) and (3).

  本发明提供了一种含有药物的脂质体，该脂质体具有活性靶向性，并确保在血液中的稳定性，可有效用于诊断和/或治疗伴随蛋白多糖产生的疾病，特别是肾脏疾病、包括(1)在生理 pH 值范围内带正电荷的碱性化合物，(2)亲水性聚合物的脂质衍生物和(3)构成脂质体的脂质，作为其膜构成成分，其中它们的构成比例为：(1)占(3)的 1 至 20 摩尔%，(2)占(3)的 0.以(1)和(3)的总和为基准，(2)的比例为 0.2 至 5 摩尔%。