6-羟基-7-甲基异喹啉-1(2H)-酮 | 940890-82-4

• 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: 6-羟基-7-甲基异喹啉-1(2H)-酮
• 英文名称: 6-hydroxy-7-methyl-2H-isoquinolin-1-one
• 英文别名: 6-Hydroxy-7-methylisoquinolin-1(2H)-one
• CAS: 940890-82-4
• 化学式: C₁₀H₉NO₂
• 分子量: 175.187
• InChiKey: YIBFKSWETOWCJC-UHFFFAOYSA-N

物化性质

• 沸点：
  499.3±45.0 °C(Predicted)
• 密度：
  1.280±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933790090

反应信息

• 作为反应物：
  描述：

  6-羟基-7-甲基异喹啉-1(2H)-酮 在 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (S)-7-methyl-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one
  参考文献：
  名称：

  Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors

  摘要：

  Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.104
• 作为产物：
  描述：

  ferulic acid 在 二苯基甲烷 、 二苯基膦叠氮化物 、 三溴化硼 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 6-羟基-7-甲基异喹啉-1(2H)-酮
  参考文献：
  名称：

  Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors

  摘要：

  Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.104

文献信息

• Isoquinoline derivatives
  申请人：Ray Christopher Peter

  公开号：US20070135479A1

  公开（公告）日：2007-06-14

  The invention relates to isoquinoline derivatives having the general Formula I wherein X is O, S or NH; Y is OH or NH 2 ; m is 0, 1 or 2; n is 1 or 2; R 1 is H, when Y is NH 2 ; or R. is H, (C 1-4 )alkyl or halogen, when Y is OH; R 2 and R 3 are independently H, (C 1-4 )alkyl or halogen; R is H or (C 1-6 )alkyl, optionally substituted with OH, (C 1-4 )-alkyloxy, (C 1-4 )alkyloxycarbonyl, (C 3-7 )cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C 6-10 )aryl, (C 6-10 )aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, (C 1-4 )alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of the isoquinoline derivatives in the treatment of ROCK-I related disorders such as hypertension, atherosclerosis and glaucoma.

  本发明涉及具有通式I的异喹啉衍生物，其中X为O、S或NH；Y为OH或NH2；m为0、1或2；n为1或2；当Y为NH2时，R1为H；或当Y为OH时，R为H、(C1-4)烷基或卤素；R2和R3独立地为H、(C1-4)烷基或卤素；R为H或(C1-6)烷基，可选地取代为OH、(C1-4)烷氧基、(C1-4)烷氧羰基、(C3-7)环烷基，可选地包含从O和S中选择的杂原子，(C6-10)芳基、(C6-10)芳氧基或包含1-3个从O、N和S中独立选择的杂原子的5-或6成员杂芳基，每个芳基或杂芳基可选地取代为1-3个从(C1-4)烷基、(C1-4)烷氧基、(C1-4)烷基磺酰基和卤素中独立选择的取代基；或其药学上可接受的盐，以及包含相同的药物组合物，以及在治疗ROCK-I相关疾病如高血压、动脉粥样硬化和青光眼中使用异喹啉衍生物。
• WO2007/65916
  申请人：——

  公开号：——

  公开（公告）日：——
• ISOQUINOLINE DERIVATIVES
  申请人：N.V. Organon

  公开号：EP1963304A1

  公开（公告）日：2008-09-03
• US7618985B2
  申请人：——

  公开号：US7618985B2

  公开（公告）日：2009-11-17
• [EN] ISOQUINOLINE DERIVATIVES<br/>[FR] DERIVES D'ISOQUINOLINE
  申请人：ORGANON NV

  公开号：WO2007065916A1

  公开（公告）日：2007-06-14

  [EN] The invention relates to isoquinoline derivatives having the general Formula (I) wherein X is O, S or NH; Y is OH or NH₂; m is 0, 1 or 2; n is 1 or 2; R₁ is H, when Y is NH₂; or R₁ is H, (C_1-4)alkyl or halogen, when Y is OH; R₂ and R₃ are independently H, (C_1-4)alkyl or halogen; R is H or (C_1-6)alkyl, optionally substituted with OH, (C_1-4)- alkyloxy, (C_1-4)alkyloxycarbonyl, (C_3-7)cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C_6-10)aryl, (C_6-10)aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C_1-4)alkyl, (C_1-4)alkyloxy, (C_1-4)alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of the isoquinoline derivatives in the treatment of ROCK-I related disorders such as hypertension, atherosclerosis and glaucoma.
  [FR] L'invention concerne des dérivés d'isoquinoline de formule générale (I), dans laquelle X représente O, S ou NH; Y représente OH ou NH₂; m vaut 0, 1 ou 2; n vaut 1 ou 2; R₁ représente H, quand Y représente NH₂; ou R₁ représente H, un alkyle (C₁-C₄) ou un halogène, quand Y représente OH; R₂ et R₃ représentent indépendamment H, un alkyle (C₁-C₄) ou un halogène; R représente H ou un alkyle (C₁-C₆) éventuellement substitué par OH, un alkyloxy (C₁-C-₄), un alkyloxycarbonyle (C_1-C₄), un cycloalkyle (C₃-C₇) qui peut éventuellement comprendre un hétéroatome choisi parmi O et S, un aryle (C₆-C₁₀), un aryloxy (C₆-C₁₀) ou un groupe hétéroaryle à cinq ou six chaînons comprenant un à trois hétéroatomes indépendamment choisis parmi O, N et S, chaque groupe aryle ou un groupe hétéroaryle étant éventuellement substitué par un à trois substituants indépendamment choisis parmi les groupes alkyle (C₁-C₄), alkyloxy (C₁-C₄), akylsulfonyle (C₁-C₄) et un halogène. L'invention porte sur les dérivés d'isoquinoline ou sur un sel pharmaceutiquement acceptable de ceux-ci. Cette invention concerne également des compositions pharmaceutiques qui comprennent ces dérivés ainsi que l'utilisation des dérivés d'isoquinoline dans le traitement de troubles liés à ROCK-I tels que l'hypertension, l'athérosclérose et le glaucome.