zopolrestat | 1355612-71-3

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: zopolrestat
• 英文别名: 2-(8-oxo-7-((5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)-7,8-dihydropyrazino[2,3-d]pyridazin-5-yl)acetic acid；(2-(8-oxo-7-((5-trifluoromethyl)-1H-benzo[d]pyridazin-2-yl)methyl)-8-dihydropyrazin[2,3-d]pyridazine-5-yl)acetic acid；AT-001；Aldose reductase-IN-1；2-[5-oxo-6-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]pyrazino[2,3-d]pyridazin-8-yl]acetic acid
• CAS: 1355612-71-3
• 化学式: C₁₇H₁₀F₃N₅O₃S
• 分子量: 421.359
• InChiKey: YRGPAXAVTDMKDK-UHFFFAOYSA-N

物化性质

• 沸点：
  632.1±65.0 °C(Predicted)
• 密度：
  1.74±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  11

制备方法与用途

生物活性方面，Aldose reductase-IN-1 是一种醛糖还原酶抑制剂，其 IC50 值为 28.9 pM。

反应信息

• 作为反应物：
  描述：

  zopolrestat 在 sodium carbonate 作用下， 以 水 为溶剂， 反应 2.0h， 以82.2%的产率得到Sodium;2-[5-oxo-6-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]pyrazino[2,3-d]pyridazin-8-yl]acetate
  参考文献：
  名称：

  SALT OF ALDOSE REDUCTASE INHIBITOR, AND PREPARATION METHOD AND APPLICATION THEREOF

  摘要：

  The present invention sets forth a salt of an aldose reductase inhibitor shown in formula A-N. The salt being able to be prepared as a crystal form, having notably improved solubility relative to the compound of formula A, having lower hygroscopicity allowing for stable existence, and thus being more easily made into a medicine than are the formula A compound or other salts.

  公开号：

  US20220127273A1
• 作为产物：
  描述：

  2,3-吡嗪二酸酐 在 甲酸 、 potassium tert-butylate 、 水 、 N,N'-羰基二咪唑 、 肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 zopolrestat
  参考文献：
  名称：

  [EN] ALDOSE REDUCTASE INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE L'ALDOSE RÉDUCTASE ET LEURS UTILISATIONS

  摘要：

  本发明涉及新型化合物及其制药组合物，以及促进皮肤健康老化、治疗皮肤疾病、治疗心血管疾病、治疗肾脏疾病、治疗血管生成异常如癌症、治疗组织损伤如非心脏组织损伤、治疗急性心肌梗死的演变和使用本发明中的化合物和组合物治疗各种其他疾病，如糖尿病并发症等。其他疾病可以包括但不限于动脉粥样硬化、冠状动脉疾病、糖尿病肾病、糖尿病神经病变、糖尿病视网膜病变、皮肤感染、周围血管疾病、中风等。

  公开号：

  WO2012009553A1

文献信息

• [EN] INHIBITORS OF ALDOSE REDUCTASE<br/>[FR] INHIBITEURS DE L'ALDOSE RÉDUCTASE
  申请人：APPLIED THERAPEUTICS INC

  公开号：WO2020205846A1

  公开（公告）日：2020-10-08

  The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, cardiomyopathy, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, galactosemia, asthma, PMM2-CDG and the like.

  本公开涉及新颖化合物及其药物组合物，以及促进皮肤健康老化、治疗皮肤疾病、心血管疾病、肾脏疾病、血管生成障碍（如癌症）、组织损伤治疗（如非心脏组织损伤）、心肌梗死演变治疗、缺血性损伤治疗以及利用本发明的化合物和组合物治疗糖尿病引起的并发症等方法。其他疾病可能包括但不限于动脉粥样硬化、心肌病、冠状动脉疾病、糖尿病肾病、糖尿病神经病变、糖尿病视网膜病变、糖尿病心肌病、皮肤感染、外周血管疾病、中风、半乳糖血症、哮喘、PMM2-CDG等。
• ALDOSE REDUCTASE INHIBITORS AND USES THEREOF
  申请人：WASMUTH Andrew

  公开号：US20130225592A1

  公开（公告）日：2013-08-29

  The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, infections of the skin, peripheral vascular disease, stroke, and the like.

  本发明涉及新型化合物及其制药组合物，以及促进皮肤健康老化、治疗皮肤疾病、治疗心血管疾病、治疗肾脏疾病、治疗血管生成障碍（如癌症）、治疗组织损伤（如非心脏组织损伤）、治疗心肌梗死发展以及使用本发明的化合物和组合物治疗其他各种疾病（如糖尿病并发症）。其他疾病可以包括但不限于动脉粥样硬化、冠状动脉疾病、糖尿病肾病、糖尿病神经病、糖尿病视网膜病变、皮肤感染、外周血管疾病、中风等。
• [EN] SOLID STATE FORMS OF AT-001 AND PROCESS FOR PREPARATION THEREOF<br/>[FR] FORMES À L'ÉTAT SOLIDE D'AT-001 ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：TEVA PHARMACEUTICALS INT GMBH

  公开号：WO2022055836A1

  公开（公告）日：2022-03-17

  The present disclosure encompasses solid state forms of AT-001, in embodiments crystalline polymorphs of AT-001 or salts or co-crystals of AT-001, processes for preparation thereof, and pharmaceutical compositions thereof.

  本公开涵盖了AT-001的固态形式，包括AT-001的结晶多形体或AT-001的盐或共晶体，其制备过程以及制药组合物。
• Aldose reductase inhibitors and uses thereof
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US10052324B2

  公开（公告）日：2018-08-21

  The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, infections of the skin, peripheral vascular disease, stroke, and the like.

  本发明涉及新型化合物及其药物组合物，以及用本发明化合物和组合物促进皮肤健康老化、治疗皮肤疾病、治疗心血管疾病、治疗肾脏疾病、治疗血管生成疾病（如癌症）、治疗组织损伤（如非心脏组织损伤）、治疗不断发展的心肌梗塞以及治疗各种其他疾病（如糖尿病引起的并发症）的方法。其他疾病包括但不限于动脉粥样硬化、冠状动脉疾病、糖尿病肾病、糖尿病神经病变、糖尿病视网膜病变、皮肤感染、外周血管疾病、中风等。
• WATER SOLUBLE SALTS OF ALDOSE REDUCTASE INHIBITORS FOR TREATMENT OF DIABETIC COMPLICATIONS
  申请人：Mylari Banavara L.

  公开号：US20140228319A1

  公开（公告）日：2014-08-14

  The present invention relates to pharmaceutically acceptable water soluble salts of aldose reductase inhibitors, 2-(8-oxo-7-((5-trifluromethyl)-1H-benzo[d]imidazol-2-yl)methyl)7,8-dihydropyrazin[2,3-d]pyridazin-5-yl)acetic acid and [4-oxo-(5-trifluoromethyl-benzothaiazol-2-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid (also known as zopolrestat), pharmaceutical compositions thereof and methods of treating diabetic complications in mammals comprising administering to mammals these salt and compositions.