6-amino-7-chloro-2H-isoquinolin-1-one | 143034-89-3

• 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: 6-amino-7-chloro-2H-isoquinolin-1-one
• CAS: 143034-89-3
• 化学式: C₉H₇ClN₂O
• 分子量: 194.62
• InChiKey: JDIXLWFCIZZRTC-UHFFFAOYSA-N

物化性质

• 沸点：
  508.4±50.0 °C(Predicted)
• 密度：
  1.427±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：
  0.0
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-amino-7-chloro-2H-isoquinolin-1-one 在 三氯氧磷 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 以55%的产率得到1,7-dichloro-isoquinolin-6-ylamine
  参考文献：
  名称：

  RHO KINASE INHIBITORS

  摘要：

  揭示了一种新颖的取代的2H-异喹啉-1-酮和3H-喹唑啉-4-酮衍生物，可用作Rho激酶的抑制剂，用于治疗通过Rho激酶活性介导或维持的各种疾病和疾病，包括心血管疾病，包含这些化合物的药物组合物，使用这些化合物的方法以及制备这些化合物的方法。

  公开号：

  US20080161297A1
• 作为产物：
  描述：

  6-乙酰氨基-7-氯-1,2-二氢异喹啉-1-酮 在 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 6-amino-7-chloro-2H-isoquinolin-1-one
  参考文献：
  名称：

  Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account

  摘要：

  Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vivo proof of concept for anti-hypertensive activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.070

文献信息

• Isoquinolinone Rho kinase inhibitors
  申请人：Bosanac Todd

  公开号：US08809326B2

  公开（公告）日：2014-08-19

  Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.

  本发明涉及一种新型的取代2H-异喹啉-1-酮和3H-喹唑啉-4-酮衍生物，可用作Rho激酶的抑制剂，用于治疗多种通过Rho激酶的活性介导或维持的疾病和疾病，包括心血管疾病，包括这些化合物的制药组合物，使用这些化合物的方法以及制备这些化合物的过程。
• Rho kinase inhibitors
  申请人：Aerie Pharmaceuticals, Inc.

  公开号：US10624882B2

  公开（公告）日：2020-04-21

  Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.

  所公开的是新型取代的 2H-isoquinolin-1-one 和 3H-quinazolin-4-one 衍生物，可作为 Rho 激酶的抑制剂，用于治疗通过 Rho 激酶的活性介导或维持的各种疾病和失调，包括心血管疾病；还公开了包含此类化合物的药物组合物、使用此类化合物的方法和制造此类化合物的工艺。
• Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 3, aryl substituted pyrrolidines
  作者：Todd Bosanac、Eugene R. Hickey、John Ginn、Mohammed Kashem、Steven Kerr、Stanley Kugler、Xiang Li、Alan Olague、Sabine Schlyer、Erick R.R. Young

  DOI：10.1016/j.bmcl.2010.04.069

  日期：2010.6

  The discovery and SAR of a series of beta-aryl substituted pyrrolidine 2H-isoquinolin-1-one inhibitors of Rho-kinase (ROCK) derived from 2 is herein described. SAR studies have shown that aryl groups in the beta-position are optimal for potency. Our efforts focused on improving the ROCK potency of this isoquinolone class of inhibitors which led to the identification of pyrrolidine 32 which demonstrated a 10-fold improvement in aortic ring (AR) potency over 2. (C) 2010 Elsevier Ltd. All rights reserved. NH
• Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 2, optimization for blood pressure reduction in spontaneously hypertensive rats
  作者：John D. Ginn、Todd Bosanac、Rhonda Chen、Charles Cywin、Eugene Hickey、Mohammed Kashem、Steven Kerr、Stanley Kugler、Xiang Li、Anthony Prokopowicz、Sabine Schlyer、James D. Smith、Michael R. Turner、Frank Wu、Erick R.R. Young

  DOI：10.1016/j.bmcl.2010.07.014

  日期：2010.9

  Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort. (C) 2010 Elsevier Ltd. All rights reserved.
• US8809326B2
  申请人：——

  公开号：US8809326B2

  公开（公告）日：2014-08-19