1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(2-methyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-yl)urea | 1163719-72-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(2-methyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-yl)urea
• 英文别名: 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-[(2-methyl-3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]naphthalen-1-yl]urea
• CAS: 1163719-72-9
• 化学式: C₂₆H₁₇F₄N₅O₃
• 分子量: 523.446
• InChiKey: CSQZPTZTXIAXKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  8-(4-aminonaphthalen-1-yloxy)-2-methylpyrido[2,3-b]pyrazin-3(4H)-one 、 2-氟-5-三氟甲基苯基异氰酸酯 以 二甲基亚砜 为溶剂， 反应 3.0h， 以61%的产率得到1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(2-methyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-yl)urea
  参考文献：
  名称：

  Novel Hinge Binder Improves Activity and Pharmacokinetic Properties of BRAF Inhibitors

  摘要：

  Mutated BRAF serine/threonine kinase is implicated in several types of cancer, with particularly high frequency in melanoma and colorectal carcinoma. We recently reported on the development of BRAF inhibitors based on a tripartite A B C system featuring art imidazo[4,5]pyridin-2-one group hinge binder. Here we present the design, synthesis, and optimization of a new series of inhibitors with a different A B C system that has been modified by the introduction of a range of novel hinge binders (A ring). The optimization of the hinge binding moiety has enabled the development of compounds with low nanomolar potencies in both BRAF inhibition and cellular assays. These compounds display optimal pharmacokinetic properties that warrant further in vivo investigations.

  DOI：

  10.1021/jm100383b

文献信息

• [EN] PYRIDO[2,3-B]PYRAZINE-8-SUBSTITUTED COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS PYRIDO[2,3-B]PYRAZINE SUBSTITUÉS EN POSITION 8 ET LEUR UTILISATION
  申请人：CANCER REC TECH LTD

  公开号：WO2009077766A1

  公开（公告）日：2009-06-25

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted 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.

  本发明一般涉及用于治疗增殖性疾病、癌症等的治疗化合物领域，更具体地涉及到本文所述的某些吡啶并[2,3-b]吡嗪-8-取代化合物，该化合物在某些情况下抑制RAF（例如BRAF）活性。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体内外抑制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患，如癌症（例如结直肠癌、黑色素瘤）等。
• Pyrido[2,3-b]pyrazin-8-substituted compounds and their use
  申请人：Institute of Cancer Research: Royal Cancer Hospital (The)

  公开号：US08198279B2

  公开（公告）日：2012-06-12

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted 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.

  本发明一般涉及治疗增生性疾病、癌症等治疗化合物领域，更具体地涉及某些在此处描述的吡啶并[2,3-b]吡嗪-8-取代化合物，其抑制 RAF (例如 B-RAF) 活性等。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制 RAF (例如 BRAF) 活性、抑制受体酪氨酸激酶 (RTK) 活性、抑制细胞增殖，以及治疗通过抑制 RAF、RTK等而改善的疾病和紊乱，如增生性疾病（例如结肠直肠癌、黑色素瘤）等。
• Pyrido[2,3-b]pyrazin-8-substituted Compounds and Their Use
  申请人：Springer Caroline Joy

  公开号：US20120238568A1

  公开（公告）日：2012-09-20

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted 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.

  本发明涉及治疗增生性疾病、癌症等的治疗化合物领域，更具体地涉及某些在此处描述的吡啶并[2,3-b]吡嗪-8-取代化合物，它们在诸多方面抑制RAF（例如B-RAF）活性。本发明还涉及包含这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制RAF（例如BRAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并用于治疗由于抑制RAF、RTK等而改善的疾病和疾病，如增生性疾病（例如结直肠癌、黑色素瘤）等。
• Pyrido[2,3-B]pyrazin-8-substituted compounds and their use
  申请人：Cancer Research Technology Limited

  公开号：US08912191B2

  公开（公告）日：2014-12-16

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted 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.

  本发明涉及治疗增殖性疾病、癌症等治疗化合物领域，更具体地说，涉及某些在此处描述的吡啶并[2,3-b]吡嗪-8-取代化合物，其在其中包括抑制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，以及使用这种化合物和组合物，无论是体内还是体外，来抑制RAF（例如BRAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并用于治疗由于抑制RAF、RTK等而改善的疾病和疾病，如增殖性疾病（例如结直肠癌、黑色素瘤）等。
• PYRIDO[2,3-B]PYRAZIN-8-SUBSTITUTED COMPOUNDS AND THEIR USE
  申请人：INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

  公开号：US20150182526A1

  公开（公告）日：2015-07-02

  The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted 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.

  本发明涉及治疗增生性疾病、癌症等的治疗化合物领域，更具体地涉及某些在此处描述的吡啶并[2,3-b]吡嗪-8-取代化合物，它们在其他方面抑制RAF（例如B-RAF）活性。本发明还涉及包含这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制RAF（例如BRAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并治疗由于抑制RAF，RTK等而改善的疾病和疾患，如癌症（例如结直肠癌，黑色素瘤）等。