6-(7-Amino-6-methoxy-5,8-dioxoquinolin-2-yl)pyridine-2-carboxylic acid | 454476-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(7-Amino-6-methoxy-5,8-dioxoquinolin-2-yl)pyridine-2-carboxylic acid
• CAS: 454476-14-3
• 化学式: C₁₆H₁₁N₃O₅
• 分子量: 325.28
• InChiKey: SXDGBNGFCMZCTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Methyl 7-bromo-2-(2'-pyridyl)quinoline-5,8-quinone-6'-carboxylate 在 sodium azide 、 sodium dithionite 、 cerium(III) chloride 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 6-(7-Amino-6-methoxy-5,8-dioxoquinolin-2-yl)pyridine-2-carboxylic acid
  参考文献：
  名称：

  Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation

  摘要：

  Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity and human disease, we initiated a program to develop PAD inhibitors as potential therapeutics for these and other diseases in which the PADs are thought to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial activity was later identified as a highly potent PAD4 inhibitor. In an effort to understand why streptonigrin is such a potent and selective PAD4 inhibitor, we explored its structure-activity relationships by examining the inhibitory effects of several analogues that mimic the A, B, C, and/or D rings of streptonigrin. We report the identification of the 7-amino-quinoline-5,8-dione core of streptonigrin as a highly potent pharmacophore that acts as a pan-PAD inhibitor. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.064

文献信息

• Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation
  作者：Christina J. Dreyton、Erin D. Anderson、Venkataraman Subramanian、Dale L. Boger、Paul R. Thompson

  DOI：10.1016/j.bmc.2013.12.064

  日期：2014.2

  Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity and human disease, we initiated a program to develop PAD inhibitors as potential therapeutics for these and other diseases in which the PADs are thought to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial activity was later identified as a highly potent PAD4 inhibitor. In an effort to understand why streptonigrin is such a potent and selective PAD4 inhibitor, we explored its structure-activity relationships by examining the inhibitory effects of several analogues that mimic the A, B, C, and/or D rings of streptonigrin. We report the identification of the 7-amino-quinoline-5,8-dione core of streptonigrin as a highly potent pharmacophore that acts as a pan-PAD inhibitor. (C) 2014 Elsevier Ltd. All rights reserved.