(R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine | 1035096-91-3

• 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: (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine
• 英文别名: N-[(3R)-pyrrolidin-3-yl]isoquinolin-5-amine
• CAS: 1035096-91-3
• 化学式: C₁₃H₁₅N₃
• 分子量: 213.282
• InChiKey: HOTGJYAYVQJOMO-LLVKDONJSA-N

物化性质

• 沸点：
  414.4±40.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine 在 三乙酰氧基硼氢化钠 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 26.0h， 生成 (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethanol L-tartaric acid salt
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF RHO-KINASE INHIBITOR COMPOUNDS
  [FR] PROCESSUS DE PRÉPARATION DE COMPOSÉS INHIBITEURS DE RHO-KINASE

  摘要：

  本发明旨在提供实用的高产率合成工艺，用于制备一般化学式III、IV、V、VII、VIII、IX、X、XII、XIV和XV的化合物。这些化合物可用作最终产品，也可用作中间体，并可进一步修改以制备其他所需产品，如rho-激酶抑制剂。本发明还涉及某些新颖化合物和/或某些化合物的新颖固体形式。

  公开号：

  WO2009154940A1
• 作为产物：
  描述：

  5-氨基异喹啉 在 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 醋酸异丙酯 、 异丙醇 为溶剂， 反应 6.5h， 生成 (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF RHO-KINASE INHIBITOR COMPOUNDS
  [FR] PROCESSUS DE PRÉPARATION DE COMPOSÉS INHIBITEURS DE RHO-KINASE

  摘要：

  本发明旨在提供实用的高产率合成工艺，用于制备一般化学式III、IV、V、VII、VIII、IX、X、XII、XIV和XV的化合物。这些化合物可用作最终产品，也可用作中间体，并可进一步修改以制备其他所需产品，如rho-激酶抑制剂。本发明还涉及某些新颖化合物和/或某些化合物的新颖固体形式。

  公开号：

  WO2009154940A1

文献信息

• [EN] METHOD FOR TREATING OPHTHALMIC DISEASES USING KINASE INHIBITOR COMPOUNDS IN PRODRUG FORMS<br/>[FR] MÉTHODE DE TRAITEMENT DE MALADIES OPHTALMIQUES À L'AIDE DE COMPOSÉS D'INHIBITEURS DE KINASE SOUS FORME DE PROMÉDICAMENTS
  申请人：INSPIRE PHARMACEUTICALS INC

  公开号：WO2012015760A1

  公开（公告）日：2012-02-02

  This invention is directed to prodrugs of rho kinase (ROCK) inhibitors. These prodrugs are in general the ester or the amide derivatives of the parent compounds. These prodrugs are often weak inhibitors of ROCK, but their parent compounds have good activities. Upon instillation into the eyes, the ester or the amide group of these prodrugs is rapidly hydrolyzed into alcohol, amine, or acid, and the prodrugs are converted into the active base compounds. The prodrugs of ROCK inhibitors provide several advantages such as delivery of higher concentrations of the active species into the target site and reduction of ocular discomfort. The invention is also directed to a method of treating ophthalmic diseases such as glaucoma, allergic conjunctivitis, macular edema, macular degeneration, and blepharitis, by administering an effective amount of a ROCK prodrug compound of Formula (I) to the eyes of the patient in need of.

  这项发明涉及罗激酶（ROCK）抑制剂的前药。这些前药通常是母化合物的酯或酰胺衍生物。这些前药通常是ROCK的弱抑制剂，但它们的母化合物具有良好的活性。将这些前药滴入眼中后，其酯或酰胺基团会迅速水解成醇、胺或酸，前药会转化为活性的基本化合物。ROCK抑制剂的前药提供了几个优点，如将更高浓度的活性物质传递到目标部位，减少眼部不适。该发明还涉及通过向需要的患者眼部给予公式（I）的ROCK前药化合物的有效量来治疗青光眼、过敏性结膜炎、黄斑水肿、黄斑变性和睑缘炎等眼科疾病的方法。
• CYTOSKELETAL ACTIVE RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
  申请人：Lampe John W.

  公开号：US20080214614A1

  公开（公告）日：2008-09-04

  The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

  本发明涉及一种合成的细胞骨架活性化合物，其为rho相关蛋白激酶的抑制剂。本发明还涉及包含此类化合物和药用载体的制药组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或病症的方法。在本发明的一个实施例中，该方法治疗增加的眼内压，如原发性开角型青光眼。该方法包括向受体施用公式I或公式II的细胞骨架活性化合物的治疗有效量，其中该量能够影响肌动蛋白相互作用，例如通过导致细胞松弛和细胞基质附着的改变。
• PROCESS FOR THE PREPARATION OF RHO-KINASE INHIBITOR COMPOUNDS
  申请人：She Jin

  公开号：US20100022775A1

  公开（公告）日：2010-01-28

  The present invention is directed to practical high-yielding synthetic processes to prepare compounds of general Formula III, IV, V, VII, VIII, IX, X, XII, XIV, and XV. Such compounds are useful as final products or can be used as intermediates and be further modified to prepare other desired products such as rho-kinase inhibitors. The present invention is also directed to certain novel compounds and/or novel solid forms of certain compounds.

  本发明涉及实用的高产率合成过程，用于制备通式III、IV、V、VII、VIII、IX、X、XII、XIV和XV的化合物。这些化合物可用作最终产品，也可用作中间体，并进一步改性以制备其他所需产品，如rho-激酶抑制剂。本发明还涉及某些新颖化合物和/或某些化合物的新颖固态形式。
• Process for the preparation of Rho-kinase inhibitor compounds
  申请人：Inspire Pharmaceuticals, Inc.

  公开号：US08158796B2

  公开（公告）日：2012-04-17

  The present invention is directed to practical high-yielding synthetic processes to prepare compounds of general Formula III, IV, V, VII, VIII, IX, X, XII, XIV, and XV. Such compounds are useful as final products or can be used as intermediates and be further modified to prepare other desired products such as rho-kinase inhibitors. The present invention is also directed to certain novel compounds and/or novel solid forms of certain compounds.

  本发明旨在提供实用的高产率合成过程，以制备通式III、IV、V、VII、VIII、IX、X、XII、XIV和XV的化合物。这些化合物可用作最终产品，也可以用作中间体，并进一步改性以制备其他所需产品，如Rho激酶抑制剂。本发明还涉及某些新颖化合物和/或某些化合物的新颖固体形式。
• Cytoskeletal active rho kinase inhibitor compounds, composition and use
  申请人：Inspire Pharmaceuticals, Inc.

  公开号：US08071779B2

  公开（公告）日：2011-12-06

  The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

  本发明涉及合成的细胞骨架活性化合物，其为rho相关蛋白激酶的抑制剂。本发明还涉及包含这种化合物和药学上可接受的载体的制药组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或症状的方法。在本发明的一种实施方式中，该方法治疗增加的眼内压，例如原发性开角型青光眼。该方法包括向受试者施用公式I或公式II的细胞骨架活性化合物的治疗有效量，其中该量有效地影响肌动蛋白相互作用，例如通过导致细胞松弛和细胞-基质粘附的改变。