3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanamide | 1253955-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanamide
• 英文别名: 3-(1,3-dioxoisoindol-2-yl)-N-isoquinolin-6-yl-2-[4-tri(propan-2-yl)silyloxyphenyl]propanamide
• CAS: 1253955-01-9
• 化学式: C₃₅H₃₉N₃O₄Si
• 分子量: 593.798
• InChiKey: OEJFCITVEXQLFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.81
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanamide 在 盐酸 、 四丁基氟化铵 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma

  摘要：

  Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (K-i = 0.2 nM) and demonstrated an effective and sustained IOP reduction for 24 h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.104
• 作为产物：
  描述：

  4-羟基苯乙酸甲酯 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 3-(1,3-dioxoisoindolin-2-yl)-N-(isoquinolin-6-yl)-2-(4-(triisopropylsilyloxy)phenyl)propanamide
  参考文献：
  名称：

  [EN] BETA-AMINO-ISOQUINOLINYL AMIDE COMPOUNDS
  [FR] COMPOSÉS AMIDES BETA-AMINO-ISOQUINOLÉINE

  摘要：

  本发明揭示了α-氧基-β-氧基-异喹啉酰胺化合物和取代苯甲酰胺化合物。具体而言，本发明提供了影响细胞中激酶功能的化合物，这些化合物可用作治疗剂或与治疗剂一起使用。本发明的化合物在治疗多种疾病和病况方面具有用途，包括眼部疾病如青光眼、心血管疾病以及以异常生长为特征的疾病，如癌症。本发明还提供含有异喹啉酰胺化合物的组合物。

  公开号：

  WO2018034702A1

文献信息

• [EN] DUAL-ACTION INHIBITORS AND METHODS OF USING SAME<br/>[FR] INHIBITEURS À DOUBLE ACTION ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AERIE PHARMACEUTICALS INC

  公开号：WO2010127329A1

  公开（公告）日：2010-11-04

  Provided are compounds, compositions, and methods for treating diseases and conditions wherein an inhibitor of a kinase, such as rho kinase (ROCK), and an inhibitor of one or more of the monoamine transporters, such as NET or SERT, act in concert to improve the condition.

  提供了治疗疾病和症状的化合物、组合物和方法，其中一种激酶抑制剂（如rho激酶（ROCK））和一种或多种单胺转运体抑制剂（如NET或SERT）共同作用以改善病情。
• [EN] BETA-AMINO-ISOQUINOLINYL AMIDE COMPOUNDS<br/>[FR] COMPOSÉS AMIDES BETA-AMINO-ISOQUINOLÉINE
  申请人：AERIE PHARMACEUTICALS INC

  公开号：WO2018034702A1

  公开（公告）日：2018-02-22

  Disclosed are alpha-axyl-beta-axmno isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing isoquinoline amide compounds.

  本发明揭示了α-氧基-β-氧基-异喹啉酰胺化合物和取代苯甲酰胺化合物。具体而言，本发明提供了影响细胞中激酶功能的化合物，这些化合物可用作治疗剂或与治疗剂一起使用。本发明的化合物在治疗多种疾病和病况方面具有用途，包括眼部疾病如青光眼、心血管疾病以及以异常生长为特征的疾病，如癌症。本发明还提供含有异喹啉酰胺化合物的组合物。
• Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma
  作者：Jill M. Sturdivant、Susan M. Royalty、Cheng-Wen Lin、Lori A. Moore、Jeffrey D. Yingling、Carmen L. Laethem、Bryan Sherman、Geoffrey R. Heintzelman、Casey C. Kopczynski、Mitchell A. deLong

  DOI：10.1016/j.bmcl.2016.03.104

  日期：2016.5

  Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (K-i = 0.2 nM) and demonstrated an effective and sustained IOP reduction for 24 h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension. (C) 2016 Elsevier Ltd. All rights reserved.