2-(6-methoxy-2-naphthyl)propionic acid N-oxysuccinimide ester | 129612-71-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(6-methoxy-2-naphthyl)propionic acid N-oxysuccinimide ester
• 英文别名: naproxen N-hydroxysuccinimide ester；N-[(+)-6-Methoxy-α-methyl-2-naphthaleneacetyloxy]-succinimide；d-2-(6-methoxy-2-naphthyl)-propionic acid N-hydroxysuccinimide ester；(2,5-Dioxopyrrolidin-1-yl) 2-(6-methoxynaphthalen-2-yl)propanoate
• CAS: 129612-71-1
• 化学式: C₁₈H₁₇NO₅
• 分子量: 327.337
• InChiKey: RGQJSRAYQQBAFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(6-methoxy-2-naphthyl)propionic acid N-oxysuccinimide ester 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 36.0h， 生成 2-(6-methoxy-2-naphthyl)propionylglycine
  参考文献：
  名称：

  布洛芬和萘普生的酯和酰胺前药：合成，抗炎活性和胃肠道毒性。

  摘要：

  合成了布洛芬（1）和萘普生（16）的酯和酰胺前药，并评估其抗炎活性和胃肠道毒性。前药的化学结构在亲脂性和对水解的反应性方面有所不同。小鼠中乙酸诱导的扭体的抑制表明前药7、15、19和20表现出比母体化合物明显更好的活性（p小于0.01）。确定大鼠口服1和16以及前药5、18、21和22后在胃粘膜中形成的平均溃疡数。除甘氨酸酰胺21外，所有前药对胃粘膜的刺激​​性均显着低于1或16。

  DOI：

  10.1002/jps.2600810210
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 2-(6-甲氧基-2-萘基)丙酸 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 2-(6-methoxy-2-naphthyl)propionic acid N-oxysuccinimide ester
  参考文献：
  名称：

  布洛芬和萘普生的酯和酰胺前药：合成，抗炎活性和胃肠道毒性。

  摘要：

  合成了布洛芬（1）和萘普生（16）的酯和酰胺前药，并评估其抗炎活性和胃肠道毒性。前药的化学结构在亲脂性和对水解的反应性方面有所不同。小鼠中乙酸诱导的扭体的抑制表明前药7、15、19和20表现出比母体化合物明显更好的活性（p小于0.01）。确定大鼠口服1和16以及前药5、18、21和22后在胃粘膜中形成的平均溃疡数。除甘氨酸酰胺21外，所有前药对胃粘膜的刺激​​性均显着低于1或16。

  DOI：

  10.1002/jps.2600810210

文献信息

• Acylated sugar derivatives, processes for their manufacture, and their
  申请人：Ciba-Geigy Corporation

  公开号：US04640911A1

  公开（公告）日：1987-02-03

  There are described sugar derivatives of the formula I ##STR1## that have immuno-stimulating action and that contain as inventive element at least one radical A.sup.1 or A.sup.2. These radicals A.sup.1 and A.sup.2, which may be constituents of the radicals R.sup.1, R.sup.2, R.sup.4, R.sup.6, R.sup.9, R.sup.10 or R.sup.12 according to formula I, are defined as follows: A.sup.1 represents lower alkanoyl that is substituted by aryl, heteroaryl or heteroarylthio and that may be additionally substituted by an ethylene radical which, with the above-mentioned aryl or heteroaryl substituent, forms a five-membered ring or represents ortho- or ortho/meta-substituted aroyl. A.sup.2 represents lower alkoxy substituted by aryl heteroaryl or heteroarylthio. Also described are processes for the manufacture of the compounds of the formula I and novel intermediates.

  描述了具有免疫刺激作用的I式糖衍生物##STR1##，其中包含至少一个基团A.sup.1或A.sup.2作为创新元素。根据式I，这些基团A.sup.1和A.sup.2可能是基团R.sup.1、R.sup.2、R.sup.4、R.sup.6、R.sup.9、R.sup.10或R.sup.12的组分，并定义如下：A.sup.1代表被芳基、杂芳基或杂芳硫取代的低碳酰基，可以附加地被乙烯基取代，该乙烯基与上述芳基或杂芳基取代物形成五元环，或者代表邻位或邻位/间位取代的芳酰基。A.sup.2代表被芳基、杂芳基或杂芳硫取代的低烷氧基。还描述了制备式I化合物和新中间体的方法。
• 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：——
• High molecular weight prodrug derivatives of antiinflammatory drugs
  申请人：Larsen, Claus Selch

  公开号：EP0331471B1

  公开（公告）日：1992-12-16
• 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.
• SINGH, PRITPAL;HINGORANI, L. L.;TRIVEDI, G. K., INDIAN J. CHEM. B , 29,(1990) N, C. 551-555
  作者：SINGH, PRITPAL、HINGORANI, L. L.、TRIVEDI, G. K.

  DOI：——

  日期：——