4-hydroxybutyl 2-(4-isobutylphenyl)propanoate

• 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: 4-hydroxybutyl 2-(4-isobutylphenyl)propanoate
• 英文别名: 4-Hydroxybutyl 2-[4-(2-methylpropyl)phenyl]propanoate
• 化学式: C₁₇H₂₆O₃
• 分子量: 278.392
• InChiKey: LHOOMJCOKSYNPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 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-hydroxybutyl 2-(4-isobutylphenyl)propanoate 在 silver hexafluoroantimonate 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 copper(II) acetate monohydrate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 4-((2-(4-isobutylphenyl)propanoyl)oxy)butyl (E)-3-(2-(2-oxopyridin-1(2H)-yl)phenyl)acrylate
  参考文献：
  名称：

  Pyridone Directed Ru-Catalyzed Olefination of sp²(C–H) Bond Using Michael Acceptors: Creation of Drug Analogues

  摘要：

  DOI：

  10.1021/acs.joc.2c00428
• 作为产物：
  描述：

  1,4-丁二醇 、 布洛芬 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-hydroxybutyl 2-(4-isobutylphenyl)propanoate
  参考文献：
  名称：

  Pegylation Improves the Pharmacokinetics and Bioavailability of Small-Molecule Drugs Hydrolyzable by Esterases: A Study of Phospho-Ibuprofen

  摘要：

  药物的酯酶水解会加速药物的排出，从而限制药物的疗效。众所周知，聚乙二醇（PEG）与药物共价连接（聚乙二醇化）可提高许多药物的药效。我们以新型磷布洛芬（PI）为试验药剂，研究了 PI 的聚乙二醇化是否能抑制酯酶对其的水解降解；已知 PI 能抑制结肠癌的生长，其羧酸酯可被羧酸酯酶（CES）水解。我们将 mPEG-2000 共价连接到 PI（PI-PEG）上，并通过将其暴露于过表达 CES 的细胞中和给小鼠注射来研究其稳定性。我们还评估了 PI-PEG 在人类结肠癌异种移植和 Apcmin/+ 小鼠体内的抗癌功效。PI-PEG 在过表达 CES1 或 CES2 的细胞中表现稳定，而 PI 则被广泛水解（90.2 ± 0.7%，14.3 ± 1.1%，平均值 ± S.E.M.）。在小鼠体内，PI 几乎完全水解。静脉注射 PI-PEG 后，血液和结肠癌异种移植物中的 PI-PEG 含量明显增加（括号内为异种移植物值）：0-24 小时的曲线下面积 = 2351 (2621) (nmol/g) ×小时；最大 C = 1965 (886) nmol/g；最大 T = 0.08 (2) 小时。其主要水解产物布洛芬的血药浓度极低。与对照组相比，PI-PEG 可抑制 74.8% 的异种移植生长（P < 0.01），并使 Apcmin/+ 小鼠的肠道肿瘤繁殖率降低 73.1% （P < 0.01），延长了小鼠的存活率（100% 对对照组的 55.1%；P = 0.013）。Pegylation能保护PI不被酯酶水解，并改善其药代动力学。在结肠癌临床前模型中，PI-PEG 是一种安全有效的药物，值得进一步评估。

  DOI：

  10.1124/jpet.114.217208

文献信息

• PHOSPHO-ESTER DERIVATIVES AND USES THEREOF
  申请人：RIGAS Basil

  公开号：US20130225529A1

  公开（公告）日：2013-08-29

  Phospho-ester compounds and pharmaceutical compositions thereof administered by the respiratory and other routes for the prevention and/or treatment of lung and brain cancer and precancerous conditions thereof, for the treatment of pain, for the treatment of skin disorders, for treating and/or preventing inflammation-related diseases, and for the treatment and prevention of cancer.

  磷酸酯化合物及其制剂可通过呼吸道及其他途径用于预防和/或治疗肺癌和脑癌及其癌前病变条件，用于疼痛治疗，用于皮肤疾病治疗，用于治疗和/或预防与炎症相关的疾病，以及用于癌症的治疗和预防。
• COMPOUNDS AND COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF INFLAMMATION-RELATED DISORDERS, PAIN AND FEVER, SKIN DISORDERS, CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Medicon Pharmaceuticals, Inc.

  公开号：US20140315834A1

  公开（公告）日：2014-10-23

  The present invention provides novel compounds and pharmaceutical compositions for the prevention and/or treatment of cancer and precancerous conditions thereof, for the treatment of pain and fever, for the treatment of skin disorders, and for treating and/or preventing inflammation-related diseases and/or cardiovascular diseases. The compounds of the invention also have analgesic properties and anti-platelet properties. The compounds of the invention may be provided to animals, including mammals and humans, by administering a suitable pharmaceutical dose in a suitable pharmaceutical dosage form. The compounds of the invention have improved efficacy and safety, including higher potency and/or fewer or less severe side effects, than conventional therapies. The compounds of the invention comprise a biologically active moiety or portion (A) that has, or is modified to have at least one carboxyl group. The moiety A is preferably an aliphatic, aromatic or alkylaryl group, preferably derived from a non-steroidal anti-inflammatory drug or NSAID (A). The moiety A is bound to a linker moiety (B) via the carboxyl of group A and a linking atom that is selected from oxygen, nitrogen, and sulphur, to form a carboxylic ester, and amide, or a thioester, bond (X 1 ) between groups A and B. Moiety B is a single bond, an aliphatic group, a substituted benzene, or an alkylene substituted hydrocarbon chain, which in turn is bound to functional moiety Z, which facilitates access of the compound into cells. The moiety Z can comprise, for example, a phosphorous-containing group, a nitrogen-containing group, or a folic acid residue.
• US7745424B2
  申请人：——

  公开号：US7745424B2

  公开（公告）日：2010-06-29
• [EN] PHOSPHO-ESTER DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHOSPHO-ESTER ET LEURS UTILISATIONS
  申请人：RIGAS BASIL

  公开号：WO2013130625A1

  公开（公告）日：2013-09-06

  Phospho-ester compounds and pharmaceutical compositions thereof administered by the respiratory and other routes for the prevention and/or treatment of lung and brain cancer and precancerous conditions thereof, for the treatment of pain, for the treatment of skin disorders, for treating and/or preventing inflammation-related diseases, and for the treatment and prevention of cancer.
• Pyridone Directed Ru-Catalyzed Olefination of <i>sp</i>²(C–H) Bond Using Michael Acceptors: Creation of Drug Analogues
  作者：Smruti Ranjan Mohanty、Namrata Prusty、Tanmayee Nanda、Shyam Kumar Banjare、Ponneri C. Ravikumar

  DOI：10.1021/acs.joc.2c00428

  日期：2022.5.6