1-(5-(6-(hydroxymethyl)pyrimidin-4-yloxy)-1H-indol-1-yl)ethanone | 1229456-44-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-(6-(hydroxymethyl)pyrimidin-4-yloxy)-1H-indol-1-yl)ethanone
• 英文别名: 1-[5-(6-hydroxymethyl-pyrimidin-4-yloxy)-indol-1-yl]ethanone；1-(5-((6-(hydroxymethyl)pyrimidin-4-yl)oxy)-1H-indol-1-yl)ethan-1-one；1-[5-[6-(hydroxymethyl)pyrimidin-4-yl]oxyindol-1-yl]ethanone
• CAS: 1229456-44-3
• 化学式: C₁₅H₁₃N₃O₃
• 分子量: 283.287
• InChiKey: CPVYHUUDOXPBSD-UHFFFAOYSA-N

物化性质

• 沸点：
  498.3±40.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5-(6-(hydroxymethyl)pyrimidin-4-yloxy)-1H-indol-1-yl)ethanone 在 4-二甲氨基吡啶 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 33.17h， 生成 N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide
  参考文献：
  名称：

  [EN] PYRIMIDIN-4-YL)OXY)-1H-INDOLE-1-CARBOXAMIDE DERIVATIVES AND USE THEREOF
  [FR] DÉRIVÉS DE PYRIMIDINE-4-YL)OXY)-1 H-INDOLE-1-CARBOXAMIDE ET LEUR UTILISATION

  摘要：

  这项发明涉及N-(1-甲基-5-(三氟甲基)-1H-吡唑-3-基)-5-((6-((甲氨基)甲基)嘧啶-4-基)氧基)-1H-吲哚-1-甲酰胺的某些代谢产物。具体地说，本发明涉及包括这些代谢产物的药物组合物，以及其制备过程及在治疗疾病中的用途。

  公开号：

  WO2014184778A1
• 作为产物：
  描述：

  1-(5-(6-(benzyloxymethyl)pyrimidin-4-yloxy)-1H-indol-1-yl)ethanone 在 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以37.4 g的产率得到1-(5-(6-(hydroxymethyl)pyrimidin-4-yloxy)-1H-indol-1-yl)ethanone
  参考文献：
  名称：

  [EN] PYRIMIDIN-4-YL)OXY)-1H-INDOLE-1-CARBOXAMIDE DERIVATIVES AND USE THEREOF
  [FR] DÉRIVÉS DE PYRIMIDINE-4-YL)OXY)-1 H-INDOLE-1-CARBOXAMIDE ET LEUR UTILISATION

  摘要：

  这项发明涉及N-(1-甲基-5-(三氟甲基)-1H-吡唑-3-基)-5-((6-((甲氨基)甲基)嘧啶-4-基)氧基)-1H-吲哚-1-甲酰胺的某些代谢产物。具体地说，本发明涉及包括这些代谢产物的药物组合物，以及其制备过程及在治疗疾病中的用途。

  公开号：

  WO2014184778A1

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。
• PYRIMIDIN-4-YL)OXY)-1H-INDOLE-1-CARBOXAMIDE DERIVATIVES AND USE THEREOF
  申请人：GLAENZEL Ulrike

  公开号：US20150018376A1

  公开（公告）日：2015-01-15

  This invention relates to certain metabolites of N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide In particular, the present invention relates to pharmaceutical compositions comprising these metabolites, as well as processes for their preparation and their use in the treatment of diseases.

  本发明涉及N-(1-甲基-5-(三氟甲基)-1H-吡唑-3-基)-5-((6-((甲氨基)甲基)嘧啶-4-基)氧基)-1H-吲哚-1-羧酰胺的某些代谢物。具体而言，本发明涉及包含这些代谢物的制药组合物，以及它们的制备过程和在治疗疾病中的应用。
• [EN] PYRIDYLOXYINDOLES INHIBITORS OF VEGF-R2 AND USE THEREOF FOR TREATMENT OF DISEASE<br/>[FR] INHIBITEURS PYRIDYLOXYINDOLES DE VEGF-R2 ET UTILISATION THÉRAPEUTIQUE DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2010066684A3

  公开（公告）日：2010-10-14
• The Discovery of <i>N</i>-(1-Methyl-5-(trifluoromethyl)-1<i>H</i>-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1<i>H</i>-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration
  作者：Christopher M. Adams、Karen Anderson、Gerald Artman、Jean-Claude Bizec、Rosemarie Cepeda、Jason Elliott、Elizabeth Fassbender、Malay Ghosh、Shawn Hanks、Leo A. Hardegger、Vinayak P. Hosagrahara、Bruce Jaffee、Keith Jendza、Nan Ji、Leland Johnson、Wendy Lee、Donglei Liu、Fang Liu、Debby Long、Fupeng Ma、Nello Mainolfi、Erik L. Meredith、Karl Miranda、Yao Peng、Stephen Poor、James Powers、Yubin Qiu、Chang Rao、Siyuan Shen、Jeremy M. Sivak、Catherine Solovay、Peter Tarsa、Amber Woolfenden、Chun Zhang、Yiqin Zhang

  DOI：10.1021/acs.jmedchem.7b01731

  日期：2018.2.22

  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.