1-氯-4-羟基异喹啉-3-羧酸 | 223388-21-4

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 1-氯-4-羟基异喹啉-3-羧酸
• 英文名称: 1-chloro-4-hydroxyisoquinoline-3-carboxylic acid
• 英文别名: 1-chloro-4-hydroxyisoquinoline-3-carboxlic acid；1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid
• CAS: 223388-21-4
• 化学式: C₁₀H₆ClNO₃
• 分子量: 223.616
• InChiKey: OBWMAIKNSCFJKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-氯-4-羟基异喹啉-3-羧酸 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 36.0h， 生成 (R)-2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido)succinic 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
• 作为产物：
  描述：

  1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 1-氯-4-羟基异喹啉-3-羧酸
  参考文献：
  名称：

  Novel nitrogen-containing heteroaryl compounds and methods of use thereof

  摘要：

  本发明涉及适用于介导缺氧诱导因子和治疗与促红细胞生成素相关疾病的化合物，通过在体外和体内增加内源性促红细胞生成素来实现。

  公开号：

  US20040254215A1

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：ISIS INNOVATION

  公开号：WO2015092412A1

  公开（公告）日：2015-06-25

  A compound which is a pyridine or isoquinoline derivative of formula (I), or a pharmaceutically acceptable salt thereof, which is useful in the inhibition of γ- butyrobetaine hydroxylase (BBOX). The compounds are particularly useful in treatment of cardiovascular disease and diabetes. (I)

  一种化合物，是公式(I)的吡啶或异喹啉衍生物，或其药学上可接受的盐，用于抑制γ-丁酰甜菜碱羟化酶（BBOX）。这些化合物在治疗心血管疾病和糖尿病方面特别有用。
• Application of a Proteolysis/Mass Spectrometry Method for Investigating the Effects of Inhibitors on Hydroxylase Structure
  作者：Christopher J. Stubbs、Christoph Loenarz、Jasmin Mecinović、Kar Kheng Yeoh、Nicola Hindley、Benoît M. Liénard、Frank Sobott、Christopher J. Schofield、Emily Flashman

  DOI：10.1021/jm900285r

  日期：2009.5.14

  Limited proteolysis coupled to matrix-assisted laser desorption/ionization (MALDI) mass spectrometric analyses can be used to screen for compounds that alter protein structure by monitoring stabilizing/destabilizing effects with respect to the rate and nature of proteolysis. When applied to prolyl hydroxylase 2, a key enzyme involved in human oxygen sensing, the method efficiently revealed differential

  有限的蛋白水解与基质辅助激光解吸/电离 (MALDI) 质谱分析相结合，可用于通过监测与蛋白水解速率和性质有关的稳定/去稳定效应来筛选改变蛋白质结构的化合物。当应用于脯氨酰羟化酶 2（一种参与人体氧感应的关键酶）时，该方法有效地揭示了结构相似化合物和不同底物对蛋白水解稳定性的不同影响。
• Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibition
  作者：Guo-Bo Li、Jürgen Brem、Robert Lesniak、Martine I. Abboud、Christopher T. Lohans、Ian J. Clifton、Sheng-Yong Yang、Juan-Carlos Jiménez-Castellanos、Matthew B. Avison、James Spencer、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1039/c7cc02394d

  日期：——

  Crystallographic analyses of the VIM-5 metallo-β-lactamase (MBL) with isoquinoline inhibitors reveal non zinc ion binding modes. Comparison with other MBL–inhibitor structures directed addition of a zinc-binding thiol enabling identification of potent B1 MBL inhibitors. The inhibitors potentiate meropenem activity against clinical isolates harboring MBLs.

  含异喹啉抑制剂的VIM-5金属-β-内酰胺酶（MBL）的晶体学分析显示非锌离子结合模式。与其他MBL抑制剂结构的比较可直接添加锌结合的硫醇，从而鉴定出有效的B1 MBL抑制剂。抑制剂可增强美罗培南对具有MBL的临床分离株的活性。
• [EN] INHIBITORS OF NF-KB<br/>[FR] INHIBITEURS DU FACTEUR NF-KB
  申请人：PROFECTUS BIOSCIENCES INC

  公开号：WO2010111460A1

  公开（公告）日：2010-09-30

  The invention relates to compounds of formulae (1) and (2), and pharmaceutically acceptable salts thereof for the treatment of cancer, inflammation, auto-immune diseases, diabetes and diabetic complications, infection, cardiovascular disease and ischemia-reperfusion injuries.

  该发明涉及式（1）和式（2）的化合物，以及其药学上可接受的盐，用于治疗癌症、炎症、自身免疫性疾病、糖尿病和糖尿病并发症、感染、心血管疾病和缺血再灌注损伤。
• [EN] NITROGEN-CONTAINING HETEROARYL COMPOUNDS AND THEIR USE IN INCREASING ENDOGENOUS ERYTHROPOIETIN<br/>[FR] COMPOSES HETEROARYLIQUES CONTENANT DE L'AZOTE ET LEUR UTILISATION DANS L'AUGMENTATION DE L'ERYTHROPOIETINE ENDOGENE
  申请人：FIBROGEN INC

  公开号：WO2004108681A1

  公开（公告）日：2004-12-16

  The present invention relates to compounds suitable for use in mediating hypoxia inducible factor and for treating erythropoietin-associated conditions by increasing endogenous erythropoietin in vitro and in vivo.

  本发明涉及一种适用于介导缺氧诱导因子和治疗与促红细胞生成素相关疾病的化合物，通过在体外和体内增加内源性促红细胞生成素。