4-hydroxy-benzoic acid-(2-methyl-pentyl ester) | 855369-54-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-hydroxy-benzoic acid-(2-methyl-pentyl ester)
• 英文别名: 4-Hydroxy-benzoesaeure-(2-methyl-pentylester)；2-Methylpentyl 4-hydroxybenzoate
• CAS: 855369-54-9
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: ZCOWKFVVYVBLAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-benzoic acid-(2-methyl-pentyl ester) 、 3-[4-(4-Heptoxyphenyl)phenyl]propanoic acid 在 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 生成 4-[3-(4'-Heptyloxy-biphenyl-4-yl)-propionyloxy]-benzoic acid 2-methyl-pentyl ester
  参考文献：
  名称：

  Hall, A. W.; Lacey, D.; Holmes, D., Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 1994, vol. 250, p. 333 - 346

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基-1-戊醇 、 对羟基苯甲酸 在 硫酸 作用下， 以 甲苯 为溶剂， 生成 4-hydroxy-benzoic acid-(2-methyl-pentyl ester)
  参考文献：
  名称：

  Hall, A. W.; Lacey, D.; Holmes, D., Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 1994, vol. 250, p. 333 - 346

  摘要：

  DOI：

文献信息

• Metabolism and Pharmacokinetics of Oxazaphosphorines
  作者：Alan V. Boddy、S. Murray Yule

  DOI：10.2165/00003088-200038040-00001

  日期：2000.4

  The 2 most commonly used oxazaphosphorines are cyclophosphamide and ifosfamide, although other bifunctional mustard analogues continue to be investigated. The pharmacology of these agents is determined by their metabolism, since the parent drug is relatively inactive. For cyclophosphamide, elimination of the parent compound is by activation to the 4-hydroxy metabolite, although other minor pathways of inactivation also play a role. Ifosfamide is inactivated to a greater degree by dechloroethylation reactions. More robust assay methods for the 4-hydroxy metabolites may reveal more about the clinical pharmacology of these drugs, but at present the best pharmacodynamic data indicate an inverse relationship between plasma concentration of parent drug and either toxicity or antitumour effect. The metabolism of cyclophosphamide is of particular relevance in the application of high dose chemotherapy. The activation pathway of metabolism is saturable, such that at higher doses (greater than 2 to 4 g/m2) a greater proportion of the drug is eliminated as inactive metabolites. However, both cyclophosphamide and ifosfamide also act to induce their own metabolism. Since most high dose regimens require a continuous infusion or divided doses over several days, saturation of metabolism may be compensated for, in part, by auto-induction. Although a quantitative distinction may be made between the cytochrome P450 isoforms responsible for the activating 4-hydroxylation reaction and those which mediate the dechloroethylation reactions, selective induction of the activation pathway, or inhibition of the inactivating pathway, has not been demonstrated clinically. Mathematical models to describe and predict the relative contributions of saturation and autoinduction to the net activation of cyclophosphamide have been developed. However, these require careful validation and may not be applicable outside the exact regimen in which they were derived. A further complication is the chiral nature of these 2 drugs, with some suggestion that one enantiomer may have a favourable profile of metabolism over the other. That the oxazaphosphorines continue to be the subject of intensive investigation over 30 years after their introduction into clinical practice is partly because of their antitumour activity. Further advances in analytical and molecular pharmacological techniques may further optimise their use and allow rational design of more selective analogues.

  最常用的两种噁唑磷酰胺类药物是环磷酰胺和异环磷酰胺，尽管其他双功能烷化剂仍在研究中。这些药物的药理学特性由其代谢途径决定，因为母体药物相对不活跃。环磷酰胺通过激活生成4-羟基代谢物来消除母体化合物，尽管其他次要的失活途径也起作用。异环磷酰胺通过脱氯乙基化反应更大幅度地失活。更强大的4-羟基代谢物检测方法可能揭示这些药物的临床药理学更多信息，但目前最佳药效学数据显示，母体药物血浆浓度的逆向关系与毒性或抗肿瘤效应相关。环磷酰胺的代谢在应用高剂量化疗时尤为相关。代谢激活途径是可饱和的，因此在高剂量（大于2至4 g/m²）下，药物以失活代谢物的形式排出的比例更大。然而，环磷酰胺和异环磷酰胺都能诱导自身代谢。由于大多数高剂量方案需要连续输注或几天的分次给药，代谢饱和可通过自诱导部分得到补偿。尽管可以对负责激活4-羟基化反应的细胞色素P450同工酶和介导脱氯乙基化反应的同工酶进行定量区分，但临床上尚未证明选择性诱导激活途径或抑制失活途径的能力。描述和预测饱和和自诱导对环磷酰胺净激活相对贡献的数学模型已开发出来。然而，这些模型需要仔细验证，并且可能不适用于它们所衍生的给药方案之外。另一个复杂之处在于这两种药物的手性本质，有迹象表明一种对映体可能比另一种具有更有利的代谢特征。由于其抗肿瘤活性，噁唑磷酰胺类药物在引入临床实践30多年后，仍然是广泛研究的主题。进一步发展分析和分子药理学技术可能进一步优化它们的使用，并允许设计更具选择性的类似物。