Indo-Leu | 87270-41-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Indo-Leu
• 英文别名: (2S)-2-[[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]amino]-4-methylpentanoic acid
• CAS: 87270-41-5
• 化学式: C₂₅H₂₇ClN₂O₅
• 分子量: 470.953
• InChiKey: JPDAIRKBZYBYNL-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  盐酸金刚烷胺 、 Indo-Leu 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Salt metathesis for developing injectable supramolecular metallohydrogelators as a multi-drug-self-delivery system

  摘要：

  盐交换法已被利用来生成一系列基于非甾体类抗炎药物（NSAID）的锌（II）金属水凝胶，具有抗炎和抗菌特性。

  DOI：

  10.1039/c6cc07712a
• 作为产物：
  描述：

  吲哚美辛 在 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.17h， 生成 Indo-Leu
  参考文献：
  名称：

  Salt metathesis for developing injectable supramolecular metallohydrogelators as a multi-drug-self-delivery system

  摘要：

  盐交换法已被利用来生成一系列基于非甾体类抗炎药物（NSAID）的锌（II）金属水凝胶，具有抗炎和抗菌特性。

  DOI：

  10.1039/c6cc07712a

文献信息

• Multidrug-Containing, Salt-Based, Injectable Supramolecular Gels for Self-Delivery, Cell Imaging and Other Materials Applications
  作者：Rajdip Roy、Parthasarathi Dastidar

  DOI：10.1002/chem.201602429

  日期：2016.10.10

  were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary

  分子和晶体工程方法都被用于合成一类新型的多药物超分子凝胶剂。将一种著名的非甾体抗炎药吲哚美辛与6种不同的l-氨基酸偶联，生成相应的具有游离羧酸官能团的肽，然后与抗病毒药金刚烷胺，伯胺进一步反应，以1：1的比例产生六种伯一元羧酸铵盐。一半的合成盐显示出凝胶化能力，包括水凝胶化，有机凝胶化和灵巧的凝胶化。凝胶的特点是具有台式和动态流变学特性以及不同的显微技术。通过依赖温度1进一步了解凝胶化机理1 H NMR光谱，FTIR光谱，光致发光和动态光散射。对两种胶凝剂盐的单晶X射线衍射研究表明存在2D氢键网络。一种这样的灵巧的胶凝剂（能够使纯净水和水杨酸甲酯胶凝，这对于生物学应用是重要的溶剂）在机械（可逆转和可注射）和生物学（自递送）应用中都有望用于未来的含多药的可注射递送载体。
• Low-molecular-weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates
  作者：Eric J. F. Franssen、Jaco Koiter、Caroline A. M. Kuipers、Andries P. Bruins、Frits Moolenaar、Dick De Zeeuw、Wim H. Kruizinga、Richard M. Kellogg、Dirk K. F. Meijer

  DOI：10.1021/jm00085a012

  日期：1992.4

  Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)alpha-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond, and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis, using acid-sensitive linkers, is suggested as a viable alternative approach.
• Salt metathesis for developing injectable supramolecular metallohydrogelators as a multi-drug-self-delivery system
  作者：Rajdip Roy、Meduri Bhagyalalitha、Pritam Choudhury、Parthasarathi Dastidar

  DOI：10.1039/c6cc07712a

  日期：——

  Salt metathesis has been exploited to generate a series of non-steroidal anti-inflammatory drug (NSAID) based Zn(ii) metallohydrogels displaying both anti-inflammatory and anti-bacterial properties.

  盐交换法已被利用来生成一系列基于非甾体类抗炎药物（NSAID）的锌（II）金属水凝胶，具有抗炎和抗菌特性。