5-((6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)oxy)-N-(5-cyclopropylisoxazol-3-yl)-1H-indole-1-carboxamide | 1229453-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-((6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)oxy)-N-(5-cyclopropylisoxazol-3-yl)-1H-indole-1-carboxamide
• 英文别名: 5-(6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (5-cyclopropyl-isoxazol-3-yl)-amide；5-[(6-acetyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl)oxy]-N-(5-cyclopropyl-1,2-oxazol-3-yl)indole-1-carboxamide
• CAS: 1229453-47-7
• 化学式: C₂₃H₂₀N₆O₄
• 分子量: 444.45
• InChiKey: YUVGBIYMUASXPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (5-cyclopropylisoxazol-3-yl)amide 、 乙酸酐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以72%的产率得到5-((6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)oxy)-N-(5-cyclopropylisoxazol-3-yl)-1H-indole-1-carboxamide
  参考文献：
  名称：

  The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration

  摘要：

  A noninvasive topical ocular therapy for the treatment of neovascular or "wet" age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAP. related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile.

  DOI：

  10.1021/acs.jmedchem.7b01731

文献信息

• HETEROBICYCLIC CARBOXAMIDES AS INHIBITORS FOR KINASES
  申请人：ARTMANN, III Gerald David

  公开号：US20120245187A1

  公开（公告）日：2012-09-27

  The invention relates to novel organic compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in the treatment of tumour diseases and ocular neovascular diseases.

  本发明涉及一种新型有机化合物(I)及其在动物或人体治疗中的应用，包括含有化合物I的制药组合物以及利用化合物I制备用于治疗蛋白激酶依赖性疾病的制药组合物的应用，特别是在治疗增殖性疾病，如肿瘤疾病和眼部新生血管疾病方面的应用。
• Heterobicyclic Carboxamides as inhibitors for kinases
  申请人：Artmann, III Gerald David

  公开号：US20100168082A1

  公开（公告）日：2010-07-01

  The invention relates to novel organic compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in the treatment of tumour diseases and ocular neovascular diseases.

  本发明涉及一种新型有机化合物(I)及其在动物或人体治疗中的应用，包括含有化合物I的药物组合物，以及利用化合物I制备用于治疗蛋白激酶依赖性疾病的药物组合物，特别是用于治疗增殖性疾病，如肿瘤疾病和眼部新生血管疾病的治疗。
• Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease
  申请人：Novartis AG

  公开号：US10174006B2

  公开（公告）日：2019-01-08

  The present invention is directed to the provision of a multi-dose topical ophthalmic composition containing a 1H-indole-1-carboxamide and use thereof for treatment of ophthalmic disease. More specifically the present invention is directed to a multi-dose aqueous ophthalmic composition (e.g., a solution, a suspension, an emulsion or the like) containing a 1H-indole-1-carboxamide (e.g., N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide) and use thereof for treatment of an ophthalmic disease at the back of the eye such as age related macular degeneration (AMD).

  本发明旨在提供一种含有1H-吲哚-1-甲酰胺的多剂量局部眼科组合物，并将其用于治疗眼科疾病。更具体地说，本发明涉及一种含有 1H-吲哚-1-甲酰胺（例如、N-(1-甲基-5-(三氟甲基)-1H-吡唑-3-基)-5-((6-((甲基氨基)甲基)嘧啶-4-基)氧基)-1H-吲哚-1-甲酰胺)，并将其用于治疗眼球后部的眼科疾病，如年龄相关性黄斑变性(AMD)。
• PYRIDYLOXYINDOLES INHIBITORS OF VEGF-R2 AND USE THEREOF FOR TREATMENT OF DISEASE
  申请人：Novartis AG

  公开号：EP2376478B1

  公开（公告）日：2017-04-19
• TOPICAL AQUEOUS OPHTHALMIC COMPOSITIONS CONTAINING A 1H-INDOLE-1-CARBOXAMIDE DERIVATIVE AND USE THEREOF FOR TREATMENT OF OPHTHALMIC DISEASE
  申请人：Novartis AG

  公开号：US20140364392A1

  公开（公告）日：2014-12-11

  The present invention is directed to the provision of a multi-dose topical ophthalmic composition containing a 1H-indole-1-carboxamide and use thereof for treatment of ophthalmic disease. More specifically the present invention is directed to a multi-dose aqueous ophthalmic composition (e.g., a solution, a suspension, an emulsion or the like) containing a 1H-indole-1-carboxamide (e.g., N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino) methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide) and use thereof for treatment of an ophthalmic disease at the back of the eye such as age related macular degeneration (AMD).