methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(((triisopropylsilyl)oxy)methyl)phenyl)propanoate | 1253955-09-7

• 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: methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(((triisopropylsilyl)oxy)methyl)phenyl)propanoate
• 英文别名: Methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-((triisopropylsilyloxy) methyl)phenyl)propanoate；methyl 3-(1,3-dioxoisoindol-2-yl)-2-[4-[tri(propan-2-yl)silyloxymethyl]phenyl]propanoate
• CAS: 1253955-09-7
• 化学式: C₂₈H₃₇NO₅Si
• 分子量: 495.691
• InChiKey: ZVXBFYNEEWHDPI-UHFFFAOYSA-N

物化性质

• 沸点：
  560.4±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.93
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(((triisopropylsilyl)oxy)methyl)phenyl)propanoate 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 四丁基氟化铵 、 1,2-二氯乙烷 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 tert-butyl 2-(4-(hydroxymethyl)phenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate
  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-(羟甲基)苯醋酸 在 2,6-二甲基吡啶 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 4.75h， 生成 methyl 3-(1,3-dioxoisoindolin-2-yl)-2-(4-(((triisopropylsilyl)oxy)methyl)phenyl)propanoate
  参考文献：
  名称：

  SS-AMINO ACID DERIVATIVE, KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, AND USE OF THE SAME

  摘要：

  提供由Formula（I）表示的化合物，其为药用盐或酯，水合物，溶剂合物或结晶形式：Formula（I）表示的化合物为β-氨基酸衍生物，在Formula（I）中：X为单键或O；Y为NH或C=O；Z为C=O，C=S，NH，W为C或N；A为单键，O，OH，OCH2，杂环或N3；R1为H或F；R2为H，F，OH，CF3，CH2OH，CHO或；R3为H；n为0或1；m为0或1。

  公开号：

  EP3845276A1

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。
• DUAL MECHANISM INHIBITORS FOR THE TREATMENT OF DISEASE
  申请人：Aerie Pharmaceuticals, Inc.

  公开号：US20130158015A1

  公开（公告）日：2013-06-20

  Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

  提供了一些既能抑制rho激酶又能抑制单胺转运体（MAT）的化合物，这些化合物用于改善疾病状态或病情。此外，还提供了包含这些化合物的组合物。进一步提供了根据本发明给药的治疗疾病或病情的方法。其中一种疾病可能是青光眼，除了其他有益的效果外，还可以实现显著降低眼内压（IOP）的效果。
• Dual mechanism inhibitors for the treatment of disease
  申请人：Aerie Pharmaceuticals, Inc.

  公开号：US10316029B2

  公开（公告）日：2019-06-11

  Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

  提供了同时抑制rho激酶和单胺转运体（MAT）的化合物，用于改善疾病状态或病情。此外还提供了包含这些化合物的组合物。进一步提供了使用该发明的化合物治疗疾病或病情的方法。其中一种疾病可能是青光眼，除了其他有益的效果外，还可以显著降低眼内压（IOP）。
• DUAL-ACTION INHBITORS AND METHODS OF USING SAME
  申请人：deLong Mitchell A.

  公开号：US20120135984A1

  公开（公告）日：2012-05-31

  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.

  提供了化合物、组合物和方法，用于治疗疾病和情况，其中激酶抑制剂，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。
• SS-AMINO ACID DERIVATIVE, KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, AND USE OF THE SAME
  申请人：Industrial Technology Research Institute

  公开号：EP3845276A1

  公开（公告）日：2021-07-07

  A compound represented by Formula (I), a pharmaceutically acceptable salt or ester, hydrate, solvate or crystalline form thereof is provided: The compound represented by Formula (I) is a β-amino acid derivative, and in Formula (I): X is a single bond or O; Y is NH or C=O; Z is C=O, C=S, NH, W is C or N; A is a single bond, O, OH, OCH2, a heterocycle or N3; R1 is H or F; R2 is H, F, OH, CF3, CH2OH, CHO or ; R3 is H; n is 0 or 1; and m is 0 or 1.

  提供由Formula（I）表示的化合物，其为药用盐或酯，水合物，溶剂合物或结晶形式：Formula（I）表示的化合物为β-氨基酸衍生物，在Formula（I）中：X为单键或O；Y为NH或C=O；Z为C=O，C=S，NH，W为C或N；A为单键，O，OH，OCH2，杂环或N3；R1为H或F；R2为H，F，OH，CF3，CH2OH，CHO或；R3为H；n为0或1；m为0或1。