4-[(1-金刚烷羰基)氨基]丁酸 | 35091-21-5

• 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
• 中文名称: 4-[(1-金刚烷羰基)氨基]丁酸
• 英文名称: adamantanylcarbonyl-GABA
• 英文别名: 4-[(1-Adamantylcarbonyl)amino]butanoic acid；4-(adamantane-1-carbonylamino)butanoic acid
• CAS: 35091-21-5
• 化学式: C₁₅H₂₃NO₃
• mdl: MFCD00194154
• 分子量: 265.353
• InChiKey: UXQXORHKKDWVER-UHFFFAOYSA-N

物化性质

• 沸点：
  508.2±29.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.866
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  4-[(1-金刚烷羰基)氨基]丁酸 、 齐多夫定 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到5'-O-{4-[(Adamantan-1-ylcarbonyl)amino]butanoyl}-3'-azido-3'-deoxythymidine
  参考文献：
  名称：

  金刚烷作为针对不良吸收药物的脑导向药物载体。2.与1-金刚烷部分缀合的AZT衍生物。

  摘要：

  合成了通过酯键与1-金刚烷部分缀合的5种AZT（叠氮胸苷）前药，以改善AZT向中枢神经系统（CNS）的转运。在用大鼠和人血浆进行的体外降解研究中，已证明前药被酶降解并定量转化为其母体药物。AZT。通过辛醇-缓冲液分配评估，前药比AZT亲脂性高得多，并且有望轻松穿透血脑屏障（BBB）。在体内研究中，将前药静脉内施用于大鼠，尽管脑脊液中前药的量可忽略不计，但在脑组织中的前药浓度却比AZT高7至18倍。这些结果表明1-金刚烷部分向AZT的引入导致BBB渗透的增强。这种药物方法对于有效治疗人免疫缺陷病毒引起的中枢神经系统感染将是有益的。

  DOI：

  10.1002/jps.2600830407
• 作为产物：
  描述：

  1-金刚烷甲酸 在 4-二甲氨基吡啶 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.17h， 生成 4-[(1-金刚烷羰基)氨基]丁酸
  参考文献：
  名称：

  Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility

  摘要：

  Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group on the right side of carbonyl group of the amide pharmacophore substituted with an adamantyl group (such as compound 14) and a methylene carbon present between the adamantyl and amide groups were essential to produce potent inhibition of sEH. The resulting amide inhibitors have 10-30-fold better solubility and lower melting point than the corresponding urea compounds. These findings will facilitate synthesis of sEH inhibitors that are easier to formulate and more bioavailable.

  DOI：

  10.1021/jm0500929

文献信息

• GUZHOVA, S. V.;ZAJTSEV, L. M.;DANILENKO, R. I., XIMIYA FIZIOL. AKTIV. SOED., CHERNOGOLOVKA,(1989) S. 79
  作者：GUZHOVA, S. V.、ZAJTSEV, L. M.、DANILENKO, R. I.

  DOI：——

  日期：——
• Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility
  作者：In-Hae Kim、Fenton R. Heirtzler、Christophe Morisseau、Kosuke Nishi、Hsing-Ju Tsai、Bruce D. Hammock

  DOI：10.1021/jm0500929

  日期：2005.5.1

  Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group on the right side of carbonyl group of the amide pharmacophore substituted with an adamantyl group (such as compound 14) and a methylene carbon present between the adamantyl and amide groups were essential to produce potent inhibition of sEH. The resulting amide inhibitors have 10-30-fold better solubility and lower melting point than the corresponding urea compounds. These findings will facilitate synthesis of sEH inhibitors that are easier to formulate and more bioavailable.
• Adamantane as a Brain-Directed Drug Carrier for Poorly Absorbed Drug. 2. AZT Derivatives Conjugated with the 1-Adamantane Moiety
  作者：Noriko Tsuzuki、Teruo Hama、Mitsuhiro Kawada、Akihiro Hasui、Ryoji Konishi、Satoshi Shiwa、Yoshihito Ochi、Shiroh Futaki、Kouki Kitagawa

  DOI：10.1002/jps.2600830407

  日期：1994.4

  Five AZT (azidothymidine) prodrugs conjugated with the 1-adamantane moiety via an ester bond were synthesized to improve the transport of AZT into the central nervous system (CNS). In in vitro degradation studies with rat and human plasma, it was demonstrated that the prodrugs were degraded enzymatically and converted quantitatively to their parent drug. AZT. As assessed by octanol-buffer partitioning

  合成了通过酯键与1-金刚烷部分缀合的5种AZT（叠氮胸苷）前药，以改善AZT向中枢神经系统（CNS）的转运。在用大鼠和人血浆进行的体外降解研究中，已证明前药被酶降解并定量转化为其母体药物。AZT。通过辛醇-缓冲液分配评估，前药比AZT亲脂性高得多，并且有望轻松穿透血脑屏障（BBB）。在体内研究中，将前药静脉内施用于大鼠，尽管脑脊液中前药的量可忽略不计，但在脑组织中的前药浓度却比AZT高7至18倍。这些结果表明1-金刚烷部分向AZT的引入导致BBB渗透的增强。这种药物方法对于有效治疗人免疫缺陷病毒引起的中枢神经系统感染将是有益的。