methyl-(S)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)-3-phenylpropanoic acid | 1446253-08-2

• 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
• 英文名称: methyl-(S)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)-3-phenylpropanoic acid
• 英文别名: methyl (2S)-2-[(1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino]-3-phenylpropanoate
• CAS: 1446253-08-2
• 化学式: C₂₀H₁₇ClN₂O₄
• 分子量: 384.819
• InChiKey: WMZJPMICGYFSSY-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl-(S)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)-3-phenylpropanoic acid 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以92%的产率得到(S)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)-3-phenylpropanoic acid
  参考文献：
  名称：

  Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)

  摘要：

  The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallo-graphic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors.

  DOI：

  10.1021/jm400193d
• 作为产物：
  描述：

  1-氯-4-羟基异喹啉-3-羧酸甲酯 在 lithium hydroxide monohydrate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 methyl-(S)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)-3-phenylpropanoic acid
  参考文献：
  名称：

  Assay Platform for Clinically Relevant Metallo-β-lactamases

  摘要：

  Metallo-beta-lactamases (MBLs) are a growing threat to the use of almost all clinically used beta-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-beta-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (Sao Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic,substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4- chloroisoquinolinols as potential pan MBL inhibitors.

  DOI：

  10.1021/jm400769b