8-benzyloxy-5-bromo-7-chloro-quinoline

• 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: 8-benzyloxy-5-bromo-7-chloro-quinoline
• 英文别名: 8-Benzyloxy-5-bromo-7-chloro-quinoline；5-bromo-7-chloro-8-phenylmethoxyquinoline
• 化学式: C₁₆H₁₁BrClNO
• 分子量: 348.626
• InChiKey: YLFDGIHDJSIJEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 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：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-benzyloxy-5-bromo-7-chloro-quinoline 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 四丁基氟化铵 、 caesium carbonate 、 间氯过氧苯甲酸 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 0.17h， 生成 7-chloro-5-(p-tolylsulfonyl)quinolin-8-ol
  参考文献：
  名称：

  Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase

  摘要：

  A series of 8-hydroxy quinolines were identified as potent inhibitors of catechol O-methyltransferase (COMT) with selectivity for the membrane-bound form of the enzyme. Small substituents at the 7-position of the quinoline were found to increase metabolic stability without sacrificing potency. Compounds with good pharmacokinetics and brain penetration were identified and demonstrated in vivo modulation of dopamine metabolites in the brain. An X-ray cocrystal structure of compound 21 in the S-COMT active site shows chelation of the active site magnesium similar to catechol-based inhibitors. These compounds should prove useful for treatment of many neurological and psychiatric conditions associated with compromised cortical dopamine signaling.

  DOI：

  10.1021/acs.jmedchem.8b01126
• 作为产物：
  描述：

  5-溴-8-羟基喹啉 在 N-氯代丁二酰亚胺 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 52.0h， 生成 8-benzyloxy-5-bromo-7-chloro-quinoline
  参考文献：
  名称：

  [EN] COMT INHIBITING METHODS AND COMPOSITIONS
  [FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES

  摘要：

  本发明涉及一种抑制受体内COMT酶的方法，以及化合物I的公式，或其药用可接受的盐，用于治疗由COMT介导的各种疾病，包括帕金森病和/或精神分裂症。

  公开号：

  WO2016123577A1

文献信息

• [EN] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2016123577A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula (I), or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  本发明涉及一种抑制受体内COMT酶的方法，以及化合物I的公式，或其药用可接受的盐，用于治疗由COMT介导的各种疾病，包括帕金森病和/或精神分裂症。
• COMT Inhibiting Methods and Compositions
  申请人：Lieber Institute for Brain Development

  公开号：US20160222001A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  本发明涉及一种抑制受试者中COMT酶的方法，以及公式I的化合物或其药学上可接受的盐，其对于由COMT介导的各种疾病的治疗具有用处，包括帕金森病和/或精神分裂症。
• US9951057B2
  申请人：——

  公开号：US9951057B2

  公开（公告）日：2018-04-24
• Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol <i>O</i>-Methyltransferase
  作者：Ingrid Buchler、Daniel Akuma、Vinh Au、Gregory Carr、Pablo de León、Michael DePasquale、Glen Ernst、Yifang Huang、Martha Kimos、Anna Kolobova、Michael Poslusney、Huijun Wei、Dominique Swinnen、Florian Montel、Florence Moureau、Emilie Jigorel、Monika-Sarah E. D. Schulze、Martyn Wood、James C. Barrow

  DOI：10.1021/acs.jmedchem.8b01126

  日期：2018.11.8

  A series of 8-hydroxy quinolines were identified as potent inhibitors of catechol O-methyltransferase (COMT) with selectivity for the membrane-bound form of the enzyme. Small substituents at the 7-position of the quinoline were found to increase metabolic stability without sacrificing potency. Compounds with good pharmacokinetics and brain penetration were identified and demonstrated in vivo modulation of dopamine metabolites in the brain. An X-ray cocrystal structure of compound 21 in the S-COMT active site shows chelation of the active site magnesium similar to catechol-based inhibitors. These compounds should prove useful for treatment of many neurological and psychiatric conditions associated with compromised cortical dopamine signaling.