1,4-dichloro-5-nitroisoquinoline | 928665-18-3

• 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: 1,4-dichloro-5-nitroisoquinoline
• 英文别名: 1,4-Dichloro-5-nitroisoquinoline
• CAS: 928665-18-3
• 化学式: C₉H₄Cl₂N₂O₂
• 分子量: 243.049
• InChiKey: CLLCZHHQZKCOHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  15
• 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：
  58.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-dichloro-5-nitroisoquinoline 在 吡啶 、 盐酸 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， -5.0~80.0 ℃ 、103.42 kPa 条件下， 反应 16.5h， 生成 N-(1-((4-chloro-1-methoxyisoquinolin-5-yl)sulfonyl)-6-cyanoindolin-4-yl)acetamide
  参考文献：
  名称：

  ROCK KINASE INHIBITORS

  摘要：

  本发明涉及抑制ROCK活性的化合物。具体来说，本发明涉及化合物、药物组合物和使用方法，例如抑制ROCK活性的方法和利用本发明的化合物和药物组合物治疗脑室性血管畸形综合征（CCM）和心血管疾病的方法。

  公开号：

  US20200140412A1
• 作为产物：
  描述：

  4-氯异喹啉 在 硫酸 、 potassium nitrate 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 氯仿 、 Petroleum ether 为溶剂， 反应 36.0h， 生成 1,4-dichloro-5-nitroisoquinoline
  参考文献：
  名称：

  ROCK KINASE INHIBITORS

  摘要：

  本发明涉及抑制ROCK活性的化合物。具体来说，本发明涉及化合物、药物组合物和使用方法，例如抑制ROCK活性的方法和利用本发明的化合物和药物组合物治疗脑室性血管畸形综合征（CCM）和心血管疾病的方法。

  公开号：

  US20200140412A1

文献信息

• Sulfonamide compound
  申请人：Matsubara Koki

  公开号：US20090048223A1

  公开（公告）日：2009-02-19

  A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G 1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G 2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; G 3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an acyl group, an acyloxy group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; Y represents a single bond, or —C(R 3 )(R 4 )— (R 3 and R 4 represent hydrogen atom, or an alkyl group, or alkylene groups which combine together to form a saturated hydrocarbon ring group); G 4 represents hydroxyl group (Y is a single group), or —N(R 1 )(R 2 ) (R 1 and R 2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a saturated heterocyclic group, an alkylsulfonyl group, an acyl group, or an amidino group); G 5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

  由以下化学式表示的化合物：[A代表含氮饱和环；m表示0到2的整数；n表示1到4的整数；G1代表氢原子、氯原子、羟基、烷氧基或氨基；G2代表卤原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷氧羰基、酰基、乙酰氧基、烷基磺基、烷基磺酰基或芳基；G3代表氢原子、卤原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷氧羰基、酰基、乙酰氧基、烷基磺基、烷基磺酰基或芳基；Y代表单键，或-C(R3)(R4)-（R3和R4代表氢原子、烷基或烷烯基，它们结合在一起形成饱和碳氢环基）；G4代表羟基（Y是单个基），或-N(R1)(R2)（R1和R2代表氢原子、烷基、芳基、烯基、炔基、饱和杂环基、烷基磺酰基、酰基或胺基）；G5是A的环构成碳原子上的取代基，代表氢原子、氟原子或烷基]或其盐、或作为前药的衍生物，其强力抑制Rho激酶。
• SULFONAMIDE COMPOUND
  申请人：Yamada Rintaro

  公开号：US20100093789A1

  公开（公告）日：2010-04-15

  A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G 1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G 2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G 3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G 4 represents hydroxyl group, or —N(R 1 )(R 2 ) (R 1 and R 2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G 5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

  化合物由以下公式表示(1) [A代表含氮饱和环；m表示0到2的整数；n表示1到4的整数；G1代表氢原子、氯原子、羟基、烷氧基或氨基；G2代表卤原子、羟基、氰基、羧基、烷基、烯基等；G3代表氢原子、卤原子、羟基、氰基、羧基、烷基、烯基等；G4代表羟基，或-N(R1)(R2) (R1和R2代表氢原子、烷基、芳基烷基、烯基、炔基或饱和杂环基)；G5是A的环构成碳原子上的取代基，代表氢原子、氟原子或烷基]或其盐，或其作为前药的衍生物，强力抑制Rho激酶。
• SULFONAMIDE DERIVATIVE
  申请人：Asahi Kasei Pharma Corporation

  公开号：EP2130828A1

  公开（公告）日：2009-12-09

  A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an acyl group, an acyloxy group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; Y represents a single bond, or -C(R3)(R4)- (R3 and R4 represent hydrogen atom, or an alkyl group, or alkylene groups which combine together to form a saturated hydrocarbon ring group); G4 represents hydroxyl group (Y is a single group), or - N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a saturated heterocyclic group, an alkylsulfonyl group, an acyl group, or an amidino group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

  由式(1)代表的化合物[A 代表含氮饱和环；m 代表 0 至 2 的整数；n 代表 1 至 4 的整数；G1 代表氢原子、氯原子、羟基、烷氧基或氨基；G2 代表卤素原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷基亚磺酰基、烷基磺酰基或芳基；G3 代表氢原子、卤素原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷氧基羰基、酰基、酰氧基、烷基亚磺酰基、烷基磺酰基或芳基；Y 代表单键，或-C(R3)(R4)-（R3 和 R4 代表氢原子，或烷基，或结合在一起形成饱和烃环基的亚烷基）； G4 代表羟基（Y 为单个基团），或-N(R1)(R2)（R1 和 R2 代表氢原子，或烷基，或芳烷基，或烯基，或炔基，或饱和杂环基，或烷基磺酰基，或酰基，或脒基）；G5 是 A 的成环碳原子上的取代基，代表氢原子、氟原子或烷基]或其盐或其衍生物，它们是原药，能有效抑制 Rho 激酶。
• Substituted isoquinolines and phthalazines as rock kinase inhibitors
  申请人：Cervello Therapeutics LLC

  公开号：US10745381B2

  公开（公告）日：2020-08-18

  The present invention relates to indoline-based compounds that inhibit Rho-associated protein kinase (ROCK) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention.

  本发明涉及抑制Rho相关蛋白激酶（ROCK）活性的吲哚啉基化合物。特别是，本发明涉及化合物、药物组合物和使用方法，例如抑制 ROCK 活性的方法和使用本发明化合物和药物组合物治疗例如脑海绵畸形综合征（CCM）和心血管疾病的方法。
• Substituted isoquinolines as rock kinase inhibitors
  申请人：Cervello Therapeutics LLC

  公开号：US11248004B2

  公开（公告）日：2022-02-15

  The present invention relates to indoline-based compounds that inhibit Rho-associated protein kinase (ROCK) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention.

  本发明涉及抑制Rho相关蛋白激酶（ROCK）活性的吲哚啉基化合物。特别是，本发明涉及化合物、药物组合物和使用方法，例如抑制 ROCK 活性的方法和使用本发明化合物和药物组合物治疗例如脑海绵畸形综合征（CCM）和心血管疾病的方法。