10-O-octyl-7-dimethylamino-6-demethyl-6-deoxytetracycline | 1042222-57-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 10-O-octyl-7-dimethylamino-6-demethyl-6-deoxytetracycline
• CAS: 1042222-57-0
• 化学式: C₃₁H₄₃N₃O₇
• 分子量: 569.698
• InChiKey: FSKVEUMHRRTYMN-DSYHTRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  41.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  153.63
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  1-碘辛烷 、 盐酸米诺环素 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以65%的产率得到10-O-octyl-7-dimethylamino-6-demethyl-6-deoxytetracycline
  参考文献：
  名称：

  Characterization of alkanoyl-10-O-minocyclines in micellar dispersions as potential agents for treatment of human neurodegenerative disorders

  摘要：

  Minocycline is a widely used antibacterial agent. Moreover, it is also demonstrated to be effective in several neurodegenerative disorders, due to its antioxidant and anti-inflammatory activities. However, the last activity is only apparent at very high doses. in fact, minocycline poorly crosses the blood-brain barrier (BBB) due to its low lipophilicity and half-life. The present work details the physicochemical characterization of a series of alkanoyl-10-O-minocycline derivatives (2-6), which are able to produce self-assembled aggregates in aqueous solution. The n-octanol/aqueous phase lipophilicity of minocycline and its derivatives were assessed by theoretical calculation, by shake-flask method, and by reversed-phase HPLC. Moreover, we determined their affinity for membrane phospholipids measuring their HPLC retention on phospholipid-based stationary phases, the so-called "Immobilized Artificial Membranes" (IAMs). Our results indicate high lipophilicity values for the minocycline derivatives (compounds 2-6); these values and the corresponding phospholipid affinities increase with the length of the hydrocarbon moiety substituent. Furthermore, the ability of the investigated alkanoyl-10-O-minocycline derivatives to self-assemble could allow a direct administration by oral and intraperitoneal routes as supramolecular systems. The advantages are an enhancement of drug solubilization, a sustained release, and the consequent less frequent drug administration. Moreover, we can hypothesize the potential solubilization in the micellar core of other poorly water soluble drugs which could improve the therapeutic effects of the pharmaceutical formulation in a combined therapy. Given the high lipophilicity of the title derivatives, they can be supposed to offer higher half-life and a better BBB penetration than minocycline. Since the new derivatives retain the structural features related to the antioxidant and anti-inflammatory effects of minocycline, they can be regarded not only as long-acting antimicrobial agents but also as candidate drugs for a targeted treatment of mental illness. (C) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2008.02.123