4-[(5-oxy-quinolinyl-8-amino)carbonyl-amino-(1-N-phenyl-3-t-butyl-pyrazol-5-yl)]-pyridin-5,6-imidazolone | 1192261-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[(5-oxy-quinolinyl-8-amino)carbonyl-amino-(1-N-phenyl-3-t-butyl-pyrazol-5-yl)]-pyridin-5,6-imidazolone
• 英文别名: 1-(5-Tert-butyl-2-phenylpyrazol-3-yl)-3-[5-[(2-oxo-1,3-dihydroimidazo[4,5-b]pyridin-7-yl)oxy]quinolin-8-yl]urea
• CAS: 1192261-30-5
• 化学式: C₂₉H₂₆N₈O₃
• 分子量: 534.577
• InChiKey: PXVWKAMYEXONBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(8-N-BOC-amino-quinolinyl-5-oxy)-5,6-diamino-pyridine 在 吡啶 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 22.5h， 生成 4-[(5-oxy-quinolinyl-8-amino)carbonyl-amino-(1-N-phenyl-3-t-butyl-pyrazol-5-yl)]-pyridin-5,6-imidazolone
  参考文献：
  名称：

  [EN] ARYL-QUINOLYL COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS ARYL-QUINOLÉYLE ET LEUR UTILISATION

  摘要：

  本发明一般涉及治疗增殖性疾病、癌症等的治疗化合物领域，更具体地涉及本文所述的某些芳基喹啉化合物，该化合物在诸多方面抑制了RAF（例如B-RAF）活性。本发明还涉及包含这种化合物的药物组合物，以及利用这种化合物和组合物在体外和体内抑制RAF（例如BRAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并用于治疗通过抑制RAF、RTK等而得到改善的疾病和疾病，如癌症（例如结直肠癌、黑色素瘤）等。

  公开号：

  WO2009130487A1

文献信息

• [EN] 1 -(5-TERT-BUTYL-2-ARYL-PYRAZOL-3-YL)-3-[2-FLUORO-4-[(3-OXO-4H-PYRIDO[2, 3-B]PYRAZIN-8-YL)OXY]PHENYL]UREA DERIVATIVES AS RAF INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE 1-(5-TERT-BUTYL-2-ARYL-PYRAZOL-3-YL)-3-[2-FLUORO-4-[(3-OXO-4H-PYRIDO[2, 3-B]PYRAZIN-8-YL)OXY]PHÉNYL]URÉE EN TANT QU'INHIBITEURS DE RAF POUR LE TRAITEMENT D'UN CANCER
  申请人：CANCER REC TECH LTD

  公开号：WO2015075483A1

  公开（公告）日：2015-05-28

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)- 3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as "TBAP compounds") that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of mutant BRAF; disorders ameliorated by the inhibition of BRAF and CRAF; disorders associated with RAS mutations and/or MAPK pathway activation; disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK; etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些1-(5-叔丁基-2-芳基吡唑-3-基)-3-[2-氟-4-[(3-氧代-4H-吡啶[2,3-b]吡嗪-8-基)氧基]苯基]脲类化合物（以下简称“TBAP化合物”），其中包括抑制RAF（例如BRAF，CRAF等）的化合物。本发明还涉及包含这样的化合物的制药组合物，以及使用这样的化合物和组合物在体内外抑制RAF（例如BRAF，CRAF等）和治疗包括增生性疾病、癌症（包括恶性黑色素瘤、结肠直肠癌、胰腺腺癌）、炎症、免疫性疾病、病毒感染、纤维化疾病、与RAF突变形式相关的疾病（例如BRAF，CRAF等）、通过抑制RAF改善的疾病（例如BRAF，CRAF等）、通过抑制突变BRAF改善的疾病、通过抑制BRAF和CRAF改善的疾病、与RAS突变和/或MAPK途径激活相关的疾病、通过抑制SRC、p38、FGFRA、VEGFR-2（KDR）和/或LCK改善的疾病等。
• 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido [2, 3-B]pyrazin- 8-yl)oxy]phenyl]urea derivatives as RAF inhibitors for the treatment of cancer
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US10167282B2

  公开（公告）日：2019-01-01

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as “TBAP compounds”) that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of mutant BRAF; disorders ameliorated by the inhibition of BRAF and CRAF; disorders associated with RAS mutations and/or MAPK pathway activation; disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK; etc.

  本发明一般涉及治疗化合物领域。更具体地说，本发明涉及某些 1-(5-叔丁基-2-芳基-吡唑-3-基)-3-[2-氟-4-[(3-氧代-4H-吡啶并[2,3-b]吡嗪-8-基)氧基]苯基]脲化合物（本文称为 "TBAP 化合物"），除其他外，这些化合物可抑制 RAF（如 BRAF、CRAF 等）。本发明还涉及包含此类化合物的药物组合物，以及此类化合物和组合物在体外和体内抑制 RAF（如 BRAF、CRAF 等）和治疗包括以下疾病在内的疾病的用途：增殖性疾病；癌症（包括如恶性黑色素瘤、结肠癌等）、恶性黑色素瘤、结肠直肠癌、胰腺腺癌）；炎症；免疫紊乱；病毒感染；纤维化紊乱；与 RAF（如 BRAF、CRAF 等）突变形式相关的紊乱、BRAF、CRAF 等）；抑制 RAF（如 BRAF、CRAF 等）可改善的疾病；抑制突变型 BRAF 可改善的疾病；抑制 BRAF 和 CRAF 可改善的疾病；与 RAS 突变和/或 MAPK 通路激活相关的疾病；抑制 SRC、p38、FGFRA、VEGFR-2（KDR）和/或 LCK 可改善的疾病等。
• ARYL-QUINOLYL COMPOUNDS AND THEIR USE
  申请人：Cancer Research Technology Limited

  公开号：EP2285805B1

  公开（公告）日：2014-07-23
• 1-(5-TERT-BUTYL-2-ARYL-PYRAZOL-3-YL)-3-[2-FLUORO-4-[(3-OXO-4H-PYRIDO[2, 3-B]PYRAZIN-8-YL)OXY]PHENYL]UREA DERIVATIVES AS RAF INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Cancer Research Technology Ltd

  公开号：EP3074396B1

  公开（公告）日：2019-05-01
• Aryl-Quinolyl Compounds and Their Use
  申请人：Niculescu-Duvaz Ion

  公开号：US20110053946A1

  公开（公告）日：2011-03-03

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain aryl-quinolyl compounds, as described herein, which, inter alia, inhibit RAF (e.g., B-RAF) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and disorders that are ameliorated by the inhibition of RAF, RTK, etc., proliferative disorders such as cancer (e.g., colorectal cancer, melanoma), etc.