N-(4-hydroxy-2-methylquinolin-6-yl)acetamide | 501653-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(4-hydroxy-2-methylquinolin-6-yl)acetamide
• 英文别名: 6-acetamide-4-hydroxy-2-methylquinoline；N-(4-hydroxy-2-methyl-[6]quinolyl)-acetamide；N-(4-Hydroxy-2-methyl-[6]chinolyl)-acetamid；N-(4-hydroxy-2-methylquinolin-6-yl) acetamide；N-(4-hydroxy-2-methyl-6-quinolyl)acetamide；N-(2-methyl-4-oxo-1H-quinolin-6-yl)acetamide
• CAS: 501653-43-6
• 化学式: C₁₂H₁₂N₂O₂
• mdl: MFCD00455299
• 分子量: 216.239
• InChiKey: INGXYDNOMOPBLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxy-2-methylquinolin-6-yl)acetamide 在 氢溴酸 、 sodium ethanolate 作用下， 生成 2,4-dimethyl-2,3-dihydro-furo[3,2-c]quinolin-8-ylamine
  参考文献：
  名称：

  Furo and thieno quinaldines and process for making same

  摘要：

  公开号：

  US02650226A1
• 作为产物：
  描述：

  4′-氨基乙酰苯胺 以 甲醇 、 二苯醚 为溶剂， 反应 7.0h， 生成 N-(4-hydroxy-2-methylquinolin-6-yl)acetamide
  参考文献：
  名称：

  嘧啶基氨基喹啉衍生物作为DOT1L抑制剂的设计，合成及抗白血病细胞增殖活性

  摘要：

  通过在DOT1L铅抑制剂3a上进行结构修饰，设计并合成了一系列含有氨基侧链的新型嘧啶基氨基喹啉衍生物8（ai）和9（ai），以及双氨基喹啉类似物3（be）。已经评估了所有化合物的DOT1L抑制活性。结果表明，大多数化合物具有很强的抗DOT1L活性。化合物3e，8h和9e是IC 50每种类别中最有潜力的化合物值分别为1.06±0.35μM，5.72±1.56μM和3.55±1.28μM。此类抑制剂通过基于表面等离振子共振（SPR）的结合测定表达了与DOT1L的显着结合相互作用。分子对接实验的结果表明它们可以占据DOT1L的SAM结合口袋。与3a和3e的化合物相比，化合物8h和9e对MLL重排的MV4-11细胞和非MLL重排的Kasumi-1细胞均表现出更好的抑制活性，但选择性较差。，这表明引入氨基侧链可能有助于其抗白血病细胞的增殖活性，这可能是由于脂肪溶解度的提高所致。此外，在qRT-PCR

  DOI：

  10.1016/j.bioorg.2018.07.022

文献信息

• Small molecule antagonists of cell-surface heparan sulfate and heparin–protein interactions
  作者：Ryan J. Weiss、Philip L. S. M. Gordts、Dzung Le、Ding Xu、Jeffrey D. Esko、Yitzhak Tor

  DOI：10.1039/c5sc01208b

  日期：——

  A series of rationally designed surfen analogs were synthesized and utilized as antagonists of glycosaminoglycan–protein interactions, including the neutralization of the anticoagulant activity of fondaparinux, a synthetic pentasaccharide analog of heparin.

  一系列经过合理设计的硫烯类似物被合成并用作糖胺聚糖-蛋白质相互作用的拮抗剂，包括中和法度帕肝素（一种肝素的合成五糖类似物）的抗凝活性。
• [EN] GTPASE INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE GTPASE ET PROCEDES D'UTILISATION CORRESPONDANTS
  申请人：CHILDRENS HOSP MEDICAL CENTER

  公开号：WO2005051392A1

  公开（公告）日：2005-06-09

  The preferred embodiments generally relate to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac (Rac1, Rac2 and/or Rac3), such compositions include compounds that modulate the GTP/GDP exchange activity, along with uses for the compounds including screening for compounds which recognize Rac GTPase, and methods of treating pathological conditions associated or related to a Rho family GTPase, including Rac. The preferred embodiments also relate to methods of using such compounds, or derivatives thereof, e.g., in therapeutics, diagnostics, and as research tools.

  首选实施例通常涉及影响Rho家族GTP酶成员的GTP结合活性的方法和组合物，最好是Rac（Rac1、Rac2和/或Rac3），这些组合物包括调节GTP/GDP交换活性的化合物，以及这些化合物的用途，包括筛选识别Rac GTP酶的化合物，并用于治疗与Rho家族GTP酶（包括Rac）相关或相关的病理条件的方法。首选实施例还涉及使用这些化合物或其衍生物的方法，例如在治疗学、诊断学和作为研究工具中的用途。
• GTPase inhibitors and methods of use and crystal structure of RAC-1 GTPase
  申请人：Zheng Yi

  公开号：US20070155766A1

  公开（公告）日：2007-07-05

  The preferred embodiments generally relate to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac (Rac1, Rac2 and/or Rac3), such compositions include compounds that modulate the GTP/GDP exchange activity, along with uses for the compounds including screening for compounds which recognize Rac GTPase, and methods of treating pathological conditions associated or related to a Rho family GTPase, including Rac. The preferred embodiments also relate to methods of using such compounds, or derivatives thereof, e.g., in therapeutics, diagnostics, and as research tools.

  首选实施例通常涉及影响Rho家族GTP酶成员的GTP结合活性的方法和组合物，优选是Rac（Rac1、Rac2和/或Rac3），这些组合物包括调节GTP/GDP交换活性的化合物，以及这些化合物的用途，包括筛选识别Rac GTP酶的化合物，并用于治疗与Rho家族GTP酶（包括Rac）相关或相关的病理条件的方法。首选实施例还涉及使用这些化合物或其衍生物的方法，例如在治疗学、诊断学和作为研究工具中。
• Amide derivatives and nociceptin antagonists
  申请人：Japan Tobacco Inc.

  公开号：US06410561B1

  公开（公告）日：2002-06-25

  The present invention relates to a compound of the formula [1′] wherein R2 is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, —O—, —S— and the like, ring G is aryl, heterocyclic group and the like, R5 is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R5 may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1′] as an active ingredient. The compound [1′] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1′] as a nociceptin antagonist or analgesic.

  本发明涉及一种化合物的公式为[1′]，其中R2是可选择地由羟基、氨基等取代的较低烷基，环B是苯基、噻吩基等，E是单键，—O—，—S—等，环G是芳基、杂环基等，R5是卤原子、羟基、可选择地由卤原子等取代的较低烷基等，t为0或1至5的整数，当t为2至5的整数时，每个R5可以相同或不同，m为0或1至8的整数，n为0或1至4的整数，以及包含化合物[1′]作为活性成分的一种痛觉受体拮抗剂。该化合物[1′]由于痛觉受体拮抗作用，对于术后疼痛等剧痛具有镇痛效果。本发明还涉及某些酰胺衍生物的使用，包括化合物[1′]作为痛觉受体拮抗剂或镇痛剂。
• Process for the manufacture of diquaternary salts of pyrimidylaminoquinolines
  申请人：MURIEL RUTH CURD

  公开号：US02585972A1

  公开（公告）日：1952-02-19

  Quaternary salts of pyrimidylaminoquinolines in which either the 2-position of the pyrimidine nucleus or the 4-position of the quinoline nucleus, or both, are substituted by an amino- or lower alkylamino-group, the -NH- linking is in the 4 : 61-positions respectively, and each nucleus may be optionally substituted by alkyl groups, are obtained by heating the quaternary compound bearing ether and/or thioether groups in the above-mentioned 2- and/or 4-positions with ammonia or lower alkylamines in a solvent. In examples, pyrimidylaminoquinoline quaternary salts having methyl thio-, or benzylthio in the 2-pyrimidyl, and 4-quinoline, positions, and/or having methoxy, ethoxy, or phenoxy in the 4-quinoline position, with amino and methyl groups as other substituents are converted into the corresponding amine or alkylamine with ammonia or ethylamine in various solvents. There is described also the preparation, as starting materials, of the quaternary satls of pyrimidylamino-quinolines substituted as required above by amino, and methyl groups and having methylthio, benzylthio, alkoxy or phenoxy groups in the required positions by the condensation of the corresponding halogenated pyrimidine ether or thioether with an aminoquinoline, or the halogenated pyrimidine with an aminoquinoline ether or thioether, non-reacting amino groups being acetylated and later hydrolysed, if necessary, and with intermediate or subsequent conversion to the quaternary salts. 6-Acetylamino and 6-amino-4-methyl, 4-benzylthio-ethers, or 4-methyl, ethyl and phenyl ethers of quinoline or quinaldine are obtained by the action of the corresponding mercaptan-, alcohol- or phenol-sodium salt or a mixture producing these, on the 4-halogen- or 4-hydroxy-quinoline compound, followed if necessary by hydrolysing the acetylamino-group. Specifications 634,531, 634,818, 658,203 and 658,204 are referred to.

  2-吡咯啉基氨基喹啉的第四价盐，在其中吡咯啉核的2-位置或喹啉核的4-位置或两者都被氨基或较低的烷基氨基取代，-NH-连接分别在4:6或1-位置，每个核也可以选择性地被烷基取代。通过在溶剂中用氨或较低的烷基胺加热带有醚和/或硫醚基团的第四价化合物，可以获得这些盐。例如，具有2-吡咯啉中甲硫基或苄基硫基和4-喹啉位置的吡咯啉基氨基喹啉四价盐，并/或具有4-喹啉位置的甲氧基、乙氧基或苯氧基，具有氨基和甲基基团作为其他取代基的盐，可以用氨或乙基胺在各种溶剂中转化为相应的胺或烷基胺。还描述了作为起始材料的吡咯啉基氨基喹啉的第四价盐，这些盐如上所述被氨基和甲基基团取代，并在所需位置具有甲硫基、苄基硫基、烷氧基或苯氧基，通过相应卤代吡咯啉醚或硫醚和氨基喹啉的缩合或卤代吡咯啉和氨基喹啉醚或硫醚，非反应性氨基被乙酰化，如果需要，后来水解，并通过中间或后续转化成第四价盐。通过在4-卤代或4-羟基喹啉化合物上作用相应的巯基醇盐、醇盐或酚盐或产生这些的混合物，然后如有必要水解乙酰氨基基团，可以获得6-乙酰氨基和6-氨基-4-甲基、4-苄基硫醚、或4-甲基、乙基和苯基醚的喹啉或喹啉醛醚。参考规范634,531、634,818、658,203和658,204。