5-amino-3-(1-methylcyclopropyl)-pyrazole-1-carboxylic acid tert-butyl ester | 1229454-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-3-(1-methylcyclopropyl)-pyrazole-1-carboxylic acid tert-butyl ester
• 英文别名: 5-Amino-3-(1-methyl-cyclopropyl)-pyrazole-1-carboxylic acid tert-butyl ester；tert-butyl 5-amino-3-(1-methylcyclopropyl)pyrazole-1-carboxylate
• CAS: 1229454-46-9
• 化学式: C₁₂H₁₉N₃O₂
• 分子量: 237.302
• InChiKey: VSZLPQKYMBSQIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-3-(1-methylcyclopropyl)-pyrazole-1-carboxylic acid tert-butyl ester 在 2,6-二甲基吡啶 、 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 22.0h， 生成 5-((S)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-methylcyclopropyl)-2H-pyrazol-3-yl]amide
  参考文献：
  名称：

  Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

  摘要：

  The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.

  DOI：

  10.1021/acs.jmedchem.5b01227

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。
• [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
• 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
• US8242125B2
  申请人：——

  公开号：US8242125B2

  公开（公告）日：2012-08-14