N-(5-((2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide | 1005840-88-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(5-((2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide
• 英文别名: N-[5-(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy-2-methylphenyl]-2,5-dimethylpyrazole-3-carboxamide
• CAS: 1005840-88-9
• 化学式: C₁₉H₁₉N₇O₂
• 分子量: 377.406
• InChiKey: BYGRCFMSPMWPQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(5-((2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 N-[5-[2-[[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]acetyl]amino]imidazo[1,2-b]pyridazin-6-yl]oxy-2-methylphenyl]-2,5-dimethylpyrazole-3-carboxamide
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS AND USES THEREOF
  [FR] NOUVEAUX COMPOSÉS ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2014197313A3

文献信息

• [EN] CRYSTALLINE FORMS OF A THERAPEUTIC COMPOUND AND USES THEREOF<br/>[FR] FORMES CRISTALLINES D'UN COMPOSÉ THÉRAPEUTIQUE ET UTILISATIONS ASSOCIÉES
  申请人：KALA PHARMACEUTICALS INC

  公开号：WO2016086026A1

  公开（公告）日：2016-06-02

  Disclosed herein are certain crystalline forms of Compound 5, N-(5-((2-(4-(2-oxa-7- azaspiro[3.5]nonan-7-yl)butanamido)imidazo[1,2-0]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3- dimethyl-1 /-/-pyrazole-5-carboxamide, as well as pharmaceutical compositions comprising the crystalline forms. The present disclosure further relates to methods for treating or preventing diseases or disorders using the crystalline forms or pharmaceutical compositions thereof in a subject in need thereof, including diseases or disorders associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor signaling pathway (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases and ocular diseases.

  本文揭示了化合物5的某些晶体形式，化合物5是N-(5-((2-(4-(2-氧杂-7-氮杂螺[3.5]壬烷-7-基)丁酰)咪唑[1,2-0]吡啶-6-基)氧基)-2-甲基苯基)-1,3-二甲基-1/-/-吡唑-5-羧酰胺，以及包含这些晶体形式的制药组合物。本公开还涉及使用这些晶体形式或其制药组合物治疗或预防需要的受体中的疾病或障碍的方法，包括与异常或病理性血管生成和/或生长因子信号通路（例如，血管内皮生长因子（VEGF））的异常信号有关的增生性疾病和眼部疾病。
• FUSED HETEROCYCLIC DERIVATIVE AND USE THEREOF
  申请人：SAKAI Nozomu

  公开号：US20090306374A1

  公开（公告）日：2009-12-10

  The present invention provides a fused heterocyclic derivative having a potent kinase inhibitory activity and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the specification, except a particular compound, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, Raf) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, a cancer growth inhibitor or a cancer metastasis suppressor.

  本发明提供了一种具有强大的激酶抑制活性的融合杂环衍生物及其用途。该化合物由式(I)表示：其中除特定化合物或其盐外，每个符号如规范中定义，以及含有该化合物或其前药的药物剂量，该药物剂量是激酶（VEGFR、VEGFR2、PDGFR、Raf）抑制剂、血管生成抑制剂、预防或治疗癌症的药物剂量、癌症生长抑制剂或癌症转移抑制剂。
• Crystalline forms of a therapeutic compound and uses thereof
  申请人：Kala Pharmaceuticals, Inc.

  公开号：US10253045B2

  公开（公告）日：2019-04-09

  Disclosed herein are certain crystalline forms of Compound 5, N-(5-((2-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butanamido)imidazo[1,2-0]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3-dimethyl-1/-/-pyrazole-5-carboxamide, as well as pharmaceutical compositions comprising the crystalline forms. The present disclosure further relates to methods for treating or preventing diseases or disorders using the crystalline forms or pharmaceutical compositions thereof in a subject in need thereof, including diseases or disorders associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor signaling pathway (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases and ocular diseases.

  本文公开了化合物 5 N-(5-((2-(4-(2-氧杂-7-氮杂螺[3.5]壬烷-7-基)丁酰胺基)咪唑并[1,2-0]哒嗪-6-基)氧基)-2-甲基苯基)-1,3-二甲基-1/-/吡唑-5-甲酰胺的某些结晶形式，以及包含这些结晶形式的药物组合物。本公开进一步涉及在有需要的受试者中使用晶体形式或其药物组合物治疗或预防疾病或失调的方法，包括与异常或病理性血管生成和/或生长因子信号通路（如血管内皮生长因子（VEGF））的异常信号有关的疾病或失调，如增殖性疾病和眼部疾病。
• Compounds and uses thereof
  申请人：Kala Pharmaceuticals, Inc.

  公开号：US10351570B2

  公开（公告）日：2019-07-16

  The present invention provides novel compounds of any one of Formulae (I)-(IV), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of any one of Formulae (I)-(IV) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor signaling pathway (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.

  本发明提供了式(I)-(IV)中任一项的新型化合物及其药物组合物。本发明还提供了由式（I）-（IV）中任意一种化合物及其药物组合物组成的具有粘液渗透性的颗粒（如纳米颗粒）。本发明还提供了使用本发明化合物及其药物组合物治疗和/或预防与异常或病理性血管生成和/或生长因子信号通路异常信号转导（如......血管内皮生长因子）相关疾病的方法和试剂盒、血管内皮生长因子（VEGF））相关的疾病，如增殖性疾病（如癌症、良性肿瘤、炎症性疾病、自身免疫性疾病）和眼部疾病（如黄斑变性、青光眼、糖尿病视网膜病变、视网膜母细胞瘤、水肿、葡萄膜炎、干眼症、睑缘炎和手术后炎症）。
• HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF CANCER
  申请人：Kala Pharmaceuticals, Inc.

  公开号：EP3003314B1

  公开（公告）日：2019-05-15