1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylamino)pyridin-4-yloxy)phenyl)urea | 1020226-02-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylamino)pyridin-4-yloxy)phenyl)urea
• 英文别名: 1-(5-Tert-butyl-2-quinolin-6-ylpyrazol-3-yl)-3-[2-fluoro-4-[2-(methylamino)pyridin-4-yl]oxyphenyl]urea
• CAS: 1020226-02-1
• 化学式: C₂₉H₂₈FN₇O₂
• 分子量: 525.585
• InChiKey: HSSVEGBPDJILAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(4-amino-3-fluorophenoxy)-N-methylpyridin-2-amine 、 2,2,2-trichloroethyl (3-(tert-butyl)-1-(quinolin-6-yl)-1H-pyrazol-5-yl)carbamate 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylamino)pyridin-4-yloxy)phenyl)urea
  参考文献：
  名称：

  KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES

  摘要：

  本发明涉及一种在治疗高增殖性疾病和哺乳动物癌症，尤其是人类癌症方面有用的新化合物。该发明还涉及调节激酶活性的方法、药物组合物以及治疗个体的方法，包括或使用这些化合物。优选的化合物是在公式Ia-Iww中列出的活性小分子。

  公开号：

  US20080090856A1

文献信息

• [EN] METHODS AND COMPOSITIONS FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES<br/>[FR] MÉTHODES ET COMPOSITIONS POUVANT ÊTRE UTILISÉES EN VUE DU TRAITEMENT DE MALADIES MYÉLOPROLIFÉRATIVES ET D'AUTRES MALADIES PROLIFÉRATIVES
  申请人：DECIPHERA PHARMACEUTICALS LLC

  公开号：WO2013036232A2

  公开（公告）日：2013-03-14

  Compounds of the present invention find utility in the treatment of hyperproliferative diseases, mammalian cancers and especially human cancers including but not limited to malignant, melanomas, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, cervical carcinomas, metastasis of primary tumor sites secondary sites, myeloproliferative diseases, chronic myelogenous leukemia, acute lymphocytic leukemia, papillary thyroid carcinoma, non small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, thyroid cancer, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, i.e. diabetic retinopathy and age-related macular degeneration, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, human inflammation, rheumatoid spondylitis, ostero-arthritis, asthma, gouty arthritis, sepsis, septic shock, endotoxic shock, Gram-negative sepsis, toxic shock syndrome, adult respiratory distress syndrome, stroke, reperfusion injury, neural trauma, neural ischemia, psoriasis, restenosis, chronic obstructive pulmonary disease, bone resorptive diseases, graft-versus-host reaction, Crohn's disease, ulcerative colitis, inflammatory bowel disease, pyresis, and combinations thereof, a disease caused by c-ABL kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, c-KIT kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, VEGFR kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, PDGFR kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, FLT-3 kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, TIE-2 kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, TRK kinases, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, c-MET kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by a HER kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.

  本发明的化合物在治疗增生性疾病、哺乳动物癌症，特别是人类癌症方面具有实用性，包括但不限于恶性黑色素瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、宫颈癌、原发肿瘤部位和转移部位的转移、骨髓增生性疾病、慢性髓性白血病、急性淋巴细胞白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合症、胃肠道间质瘤、结肠癌、甲状腺癌、眼部疾病，包括各种视网膜病变，如糖尿病性视网膜病变和老年性黄斑变性、类风湿性关节炎、哮喘、慢性阻塞性肺疾病、人类炎症、类风湿脊柱炎、骨关节炎、痛风性关节炎、败血症、脓毒症、内毒素性休克、革兰氏阴性菌感染、毒性休克综合症、成人呼吸窘迫综合症、中风、再灌注损伤、神经创伤、神经缺血、银屑病、再狭窄、慢性阻塞性肺疾病、骨吸收性疾病、移植物抗宿主反应、克罗恩病、溃疡性结肠炎、炎症性肠病、发热和以上疾病的组合，由c-ABL激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，c-KIT激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，VEGFR激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，PDGFR激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，FLT-3激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，TIE-2激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，TRK激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，c-MET激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病，或由HER激酶、其致癌形式、异常融合蛋白和多态形式引起的疾病。
• Kinase Inhibitors Useful for the Treatment of Myleoproliferative Diseases and other Proliferative Diseases
  申请人：Flynn Daniel L.

  公开号：US20110136760A1

  公开（公告）日：2011-06-09

  The present invention is concerned with novel compounds useful in the treatment of hyperproliferative diseases and mammalian cancers, especially human cancers. The invention also pertains to methods of modulating kinase activities, pharmaceutical compositions, and methods of treating individuals, incorporating or using the compounds. The preferred compounds are active small molecules set forth in formulae Ia-Iww.

  本发明涉及一种新型化合物，可用于治疗过度增殖性疾病和哺乳动物癌症，特别是人类癌症。本发明还涉及调节激酶活性的方法、制药组合物以及治疗个体的方法，包括或使用该化合物。优选的化合物是在公式Ia-Iww中列出的活性小分子。
• METHODS AND COMPOSITIONS FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES
  申请人：Flynn Daniel L.

  公开号：US20120225057A1

  公开（公告）日：2012-09-06

  Compounds of the present invention, alone and in combination with other active agents, find utility in the treatment of hyperproliferative diseases, mammalian cancers and especially human cancers including but not limited to for example malignant melanomas, myeloproliferative diseases, chronic myelogenous leukemia, acute lymphocytic leukemia, a disease caused by c-ABL kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.

  本发明的化合物，单独或与其他活性剂联合使用，可用于治疗过度增生性疾病、哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑色素瘤、骨髓增生性疾病、慢性粒细胞白血病、急性淋巴细胞白血病、由c-ABL激酶引起的疾病、其致癌形式、异常融合蛋白和多态性蛋白。
• Inhibitors of DUX4 induction for regulation of muscle function
  申请人：Sonic Master Limited

  公开号：US11065243B2

  公开（公告）日：2021-07-20

  Disclosed are methods and compositions for the treatment of facioscapulohumeral muscular dystrophy. In some cases, the methods and compositions involve the use of kinase inhibitors include Src, Syk, Abl, Tie, Flt, ErbB, Trk, PRKDC, and Yes families to repress DUX4 expression in muscle cells. Further disclosed are methods and cell based assays for screening compounds for the treatment of facioscapulohumeral muscular dystrophy.

  所公开的是治疗面肱骨肌营养不良症的方法和组合物。在某些情况下，这些方法和组合物涉及使用包括 Src、Syk、Abl、Tie、Flt、ErbB、Trk、PRKDC 和 Yes 家族在内的激酶抑制剂来抑制肌肉细胞中 DUX4 的表达。进一步公开了用于筛选治疗面肱骨肌营养不良症的化合物的方法和基于细胞的检测方法。
• KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND OTHER PROLIFERATIVE DISEASES
  申请人：Deciphera Pharmaceuticals, LLC.

  公开号：EP2073811B1

  公开（公告）日：2015-03-11