1-Isoquinolinamidoxim | 17954-33-5

• 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
• 英文名称: 1-Isoquinolinamidoxim
• 英文别名: 1-Oximinocarbonyl-isochinolin；N-hydroxy-isoquinoline-1-carboximidic acid amide；(1,2-Dihydroisoquinolin-1-ylidene)(nitroso)methanamine；N'-hydroxyisoquinoline-1-carboximidamide
• CAS: 17954-33-5
• 化学式: C₁₀H₉N₃O
• mdl: MFCD07776379
• 分子量: 187.201
• InChiKey: PEFSLZSCHFLCTH-UHFFFAOYSA-N

物化性质

• 熔点：
  127-128.5 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  390.9±34.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 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：
  71.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Isoquinolinamidoxim 在 TEA 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 (R)-N-(1-cyclohexylethyl)-5,6-dihydroxy-2-(isoquinolin-1-yl)pyrimidine-4-carboxamide
  参考文献：
  名称：

  5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein

  摘要：

  The HIV-1 nucleocapsid (NC) protein is a small basic DNA and RNA binding protein that is absolutely necessary for viral replication and thus represents a target of great interest to develop new anti-HIV agents. Moreover, the highly conserved sequence offers the opportunity to escape the drug resistance (DR) that emerged following the highly active antiretroviral therapy (HAART) treatment. On the basis of our previous research, nordihydroguaiaretic acid 1 acts as a NC inhibitor showing moderate antiviral activity and suboptimal drug-like properties due to the presence of the catechol moieties. A bioisosteric catechol replacement approach led us to identify the S-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. Hit validation efforts led to the identification of optimized analogs, as represented by compound 28, showing improved NC inhibition and antiviral activity as well as good ADME and PK properties.

  DOI：

  10.1021/acsmedchemlett.9b00608
• 作为产物：
  描述：

  1-氰基异喹啉 在 盐酸羟胺 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 1-Isoquinolinamidoxim
  参考文献：
  名称：

  5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein

  摘要：

  The HIV-1 nucleocapsid (NC) protein is a small basic DNA and RNA binding protein that is absolutely necessary for viral replication and thus represents a target of great interest to develop new anti-HIV agents. Moreover, the highly conserved sequence offers the opportunity to escape the drug resistance (DR) that emerged following the highly active antiretroviral therapy (HAART) treatment. On the basis of our previous research, nordihydroguaiaretic acid 1 acts as a NC inhibitor showing moderate antiviral activity and suboptimal drug-like properties due to the presence of the catechol moieties. A bioisosteric catechol replacement approach led us to identify the S-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. Hit validation efforts led to the identification of optimized analogs, as represented by compound 28, showing improved NC inhibition and antiviral activity as well as good ADME and PK properties.

  DOI：

  10.1021/acsmedchemlett.9b00608

文献信息

• 3-heterocyclylpropanohydroxamic acid PCP inhibitors
  申请人：——

  公开号：US20030069291A1

  公开（公告）日：2003-04-10

  Compounds of formula (I): 1 and their salts, solvates, hydrates and prodrugs are useful PCP inhibitors, processes for making the same, compositions comprising the same, and methods of treating a PCP-mediated condition or disease using the same.

  式(I)的化合物及其盐、溶剂合物、水合物和前药是有用的PCP抑制剂，制备这些化合物的方法，包含这些化合物的组合物，以及使用这些化合物治疗PCP介导的疾病或病症的方法。
• Heterocyclic compounds for treating hepatitis C virus
  申请人：Vourloumis Dionisios

  公开号：US20050075375A1

  公开（公告）日：2005-04-07

  The invention is directed to heterocyclic compounds and pharmaceutical compositions of the same for treating Hepatitis C virus.

  这项发明涉及杂环化合物和其制备的药物组合物，用于治疗丙型肝炎病毒。
• Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors
  作者：Jesus M. Ontoria、Laura Llauger Bufi、Caterina Torrisi、Alberto Bresciani、Claudia Giomini、Michael Rowley、Sergio Serafini、Hu Bin、Wu Hao、Christian Steinkühler、Philip Jones

  DOI：10.1016/j.bmcl.2011.07.031

  日期：2011.9

  The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway. (C) 2011 Elsevier Ltd. All rights reserved.
• Iwao,M.; Kuraishi,T., Journal of Heterocyclic Chemistry, 1979, vol. 16, p. 689 - 698
  作者：Iwao,M.、Kuraishi,T.

  DOI：——

  日期：——
• IWAO M.; KURAISHI T., J. HETEROCYCL. CHEM., 1979, 16, NO 4, 689-698
  作者：IWAO M.、 KURAISHI T.

  DOI：——

  日期：——