tert-butyl N-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]carbamate | 1163720-72-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl N-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]carbamate
• 英文别名: tert-butyl 2-(methylthio)-4-(3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenylcarbamate；tert-butyl 2-(methylthio)-4-(3-oxo-3,4-dihydropyrido[3,2-b]pyrazin-8-yloxy)phenylcarbamate
• CAS: 1163720-72-6
• 化学式: C₁₉H₂₀N₄O₄S
• 分子量: 400.458
• InChiKey: QLBGKQLSNZOKIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]carbamate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以76%的产率得到8-(4-amino-3-(methylthio)phenoxy)pyrido[3,2-b]pyrazin-3(4H)-one
  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
• 作为产物：
  描述：

  3-氟-4-硝基苯酚 在 indium(III) chloride 、 palladium on activated charcoal 、 potassium tert-butylate 、 氢气 、 铁粉 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 113.5h， 生成 tert-butyl N-[2-methylsulfanyl-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]carbamate
  参考文献：
  名称：

  [EN] POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES
  [FR] DÉRIVÉS D'URÉE POLYAROMATIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES MUSCULAIRES

  摘要：

  当前的发明提供尿素衍生物，特别是具有核心结构杂环基-NH-CO-NH-芳基-O-杂环基的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或症状，如杜兴氏肌肉萎缩症、贝克氏肌肉萎缩症、虚弱或肌肉萎缩症。

  公开号：

  WO2021013712A1

文献信息

• [EN] POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES<br/>[FR] DÉRIVÉS D'URÉE POLYAROMATIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES MUSCULAIRES
  申请人：ANAGENESIS BIOTECHNOLOGIES S A S

  公开号：WO2021013712A1

  公开（公告）日：2021-01-28

  The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.

  当前的发明提供尿素衍生物，特别是具有核心结构杂环基-NH-CO-NH-芳基-O-杂环基的化合物，用于治疗、改善、延缓、治愈和/或预防与肌肉细胞和/或卫星细胞相关的疾病或症状，如杜兴氏肌肉萎缩症、贝克氏肌肉萎缩症、虚弱或肌肉萎缩症。
• [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。
• [EN] PROCESS FOR THE PREPARATION OF 8-(4-AMINOPHENOXY)-4H-PYRIDO[2,3-B]PYRAZIN-3-ONE DERIVATIVES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE 8-(4-AMINOPHÉNOXY)- 4H-PYRIDO[2,3-B]PYRAZIN-3-ONE
  申请人：CANCER REC TECH LTD

  公开号：WO2015075482A1

  公开（公告）日：2015-05-28

  The present invention pertains generally to the field of organic chemical synthesis, and in particular to certain methods for the synthesis of 8-(4-aminophenyoxy)- 4H-pyrido[2,3-b]pyrazin-3-one and related compounds (denoted herein as (3)) from 4-(4-aminophenyoxy)pyridine-2,3-diamine and related compounds (denoted herein as (1)), by reaction with glyoxylic acid (denoted herein as (2)). The compounds (3) are useful in the synthesis of known anti-cancer agents, such as 1-(5-tert-butyl-2-(4-methyl- phenyl)-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea.

  本发明一般涉及有机化学合成领域，特别是涉及从4-(4-氨基苯氧基)吡啶-2,3-二胺及相关化合物（以下简称为（1））与甘氧酸（以下简称为（2））反应，合成8-(4-氨基苯氧基)-4H-吡啶并[2,3-b]吡嗪-3-酮及相关化合物（以下简称为（3））的某些方法。这些化合物（3）在合成已知的抗癌药物中起到作用，例如1-(5-叔丁基-2-(4-甲基苯基)-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。
• 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：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。