[[[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基]乙酰基]氨基]乙酸 | 2854-21-9

• 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
• 中文名称: [[[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基]乙酰基]氨基]乙酸
• 英文名称: Indomethacin glycine amide
• 英文别名: (2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetyl)-glycine；({[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl}amino)acetic acid；N-{[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl}glycine；indomethacin-glycine；N-<<1-(4-chlorbenzyoyl)-2-methyl-5-methoxy-indol-3-yl>-acetyl>glycin；N-{[1-(4-chlorbenzyoyl)-2-methyl-5-methoxy-indol-3-yl]-acetyl}glycin；N-((1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetyl)glycine；2-[[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]amino]acetic acid
• CAS: 2854-21-9
• 化学式: C₂₁H₁₉ClN₂O₅
• 分子量: 414.845
• InChiKey: NEAUYGMNRFJYLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  [[[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基]乙酰基]氨基]乙酸 、 C.I.酸性橙108 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 、 乙腈 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 4.0h， 以88%的产率得到indomethacin-glycine-ethanolamide
  参考文献：
  名称：

  Therapeutic compound-fatty acid conjugates

  摘要：

  本发明提供了治疗性结合物，其中包括一个治疗性化合物与来自脂肪酸的一个至三个酰基结合。这些治疗性化合物通常是非类固醇抗炎药物，包括一个羧酸基团。这些化合物涉及使用醋酸氢三甲胺或乙醇胺衍生物将来自脂肪酸的酰基与治疗性化合物连接起来。

  公开号：

  US06353124B1
• 作为产物：
  描述：

  吲哚美辛 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 三乙胺 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 [[[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基]乙酰基]氨基]乙酸
  参考文献：
  名称：

  Boltze; Brendler; Jacobi, Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 8 A, p. 1314 - 1325

  摘要：

  DOI：

文献信息

• Synthesis and characterisation of glucosamine–NSAID bioconjugates
  作者：Rachel A. Jones、Yann Thillier、Siva S. Panda、Nicole Rivera Rosario、C. Dennis Hall、Alan R. Katritzky

  DOI：10.1039/c4ob01681e

  日期：——

  Synthetic strategies to prepare non-steroidal anti-inflammatory drug–glucosamine bioconjugates.

  合成策略以制备非甾体抗炎药物 - 葡萄糖胺生物结合物。
• Synthesis of COX-2 and FAAH inhibitors
  申请人：Bartolini Wilmin

  公开号：US20050234244A1

  公开（公告）日：2005-10-20

  Methods for preparing indoles that are useful COX-2 inhibitors and intermediates useful in such methods are described.

  描述了制备对COX-2抑制剂有用的吲哚和在这些方法中有用的中间体的方法。
• Singh; Hingorani; Trivedi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 6, p. 551 - 555
  作者：Singh、Hingorani、Trivedi

  DOI：——

  日期：——
• 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.
• WO2006/99685
  申请人：——

  公开号：——

  公开（公告）日：——