L-α-谷氨酰-S-(1,4-二羟基-3-甲基萘-2-基)-L-半胱氨酰甘氨酸 | 88467-65-6

• 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: L-α-谷氨酰-S-(1,4-二羟基-3-甲基萘-2-基)-L-半胱氨酰甘氨酸
• 英文名称: 2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone
• 英文别名: (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(1,4-dihydroxy-3-methylnaphthalen-2-yl)sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 88467-65-6
• 化学式: C₂₁H₂₅N₃O₈S
• 分子量: 479.511
• InChiKey: AELCICNFWFTRPE-KBPBESRZSA-N

物化性质

• 沸点：
  920.0±65.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  225
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  甲萘醌 、 谷胱甘肽杂质08 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 以57%的产率得到L-α-谷氨酰-S-(1,4-二羟基-3-甲基萘-2-基)-L-半胱氨酰甘氨酸
  参考文献：
  名称：

  Indoleamine 2,3-Dioxygenase Is the Anticancer Target for a Novel Series of Potent Naphthoquinone-Based Inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K-i = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation.

  DOI：

  10.1021/jm7014155

文献信息

• Mechanism of antifeedant activity of plumbagin, a compound concerning the chemical defense in carnivorous plant
  作者：Takashi Tokunaga、Noboru Takada、Minoru Ueda

  DOI：10.1016/j.tetlet.2004.07.094

  日期：2004.9

  Dionaea muscipula Ellis accumulates a large amount of plumbagin (1), which operates as an antifeedant against predators. Content of I reached 0.5% weight of the fresh trap lobes. It was found that other carnivorous plants also accumulated similar naphthoquinone-type strong antifeedant. Thus, naphthoquinone analogs are widely used as an antifeedant among the carnivorous plants. By using several analogs of 1, we clarified that both the high volatility and high redox potential of I are important for its strong antifeedant activity. It was known that plumbagin stimulates the mitochondrial electron transport system as a result of intercepting electrons. These results suggested that the Droseraceae family possesses a universal defensive mechanism against predators, that is, accumulation of volatile naphthoquinone with high redox potential as defensive substance. Thus, it is estimated that highly volatile naphthoquinone of moderately high redox potential would be used as an antifeedant of weak toxicity. (C) 2004 Elsevier Ltd. All rights reserved.
• Indoleamine 2,3-Dioxygenase Is the Anticancer Target for a Novel Series of Potent Naphthoquinone-Based Inhibitors
  作者：Sanjeev Kumar、William P. Malachowski、James B. DuHadaway、Judith M. LaLonde、Patrick J. Carroll、Daniel Jaller、Richard Metz、George C. Prendergast、Alexander J. Muller

  DOI：10.1021/jm7014155

  日期：2008.3.1

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K-i = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation.