(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one | 1453847-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
• 英文别名: 1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]pyridin-2-one
• CAS: 1453847-59-0
• 化学式: C₂₁H₁₈ClFN₆O₂
• 分子量: 440.864
• InChiKey: TYDMCOHVPUYYGK-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-3-氟苯甲醛 在 咪唑 、 AD-mix-β 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 仲丁醇 、 mineral oil 、 叔丁醇 为溶剂， 反应 35.67h， 生成 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  [EN] SERINE/THREONINE KINASE INHIBITORS
  [FR] INHIBITEURS DE LA SÉRINE / THRÉONINE KINASE

  摘要：

  提供了公式I或其立体异构体、互变异构体、前药或药用盐，这些化合物可用于治疗高增殖、疼痛和炎症性疾病。公开了使用公式I或其立体异构体、互变异构体、前药或药用盐在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗这些疾病或相关病理状况的方法。

  公开号：

  WO2013130976A1

文献信息

• SERINE/THREONINE KINASE INHIBITORS
  申请人：Array BioPharma Inc.

  公开号：US20180127393A1

  公开（公告）日：2018-05-10

  Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  提供了公式I或其立体异构体、互变异构体、前药或药物可接受的盐的化合物，用于治疗过度增殖、疼痛和炎症性疾病。公开了使用公式I或其立体异构体、互变异构体、前药或药物可接受的盐的化合物的方法，用于哺乳动物细胞中的体外、体内或原位诊断、预防或治疗此类疾病或相关病理条件。
• USE OF A COMBINATION OF A MEK INHIBITOR AND AN ERK INHIBITOR FOR TREATMENT OF HYPERPROLIFERATIVE DISEASES
  申请人：Genentech, Inc.

  公开号：US20150111869A1

  公开（公告）日：2015-04-23

  The invention provides combinations comprising a MEK inhibitor (such as GDC-0973 or GDC-0623), or a pharmaceutically acceptable salt thereof and an ERK inhibitor (such as GDC-0994). The combinations are particularly useful for treating hyperproliferative disorders, such as cancer.

  本发明提供了一种包含MEK抑制剂（例如GDC-0973或GDC-0623）或其药学上可接受的盐和ERK抑制剂（例如GDC-0994）的组合物。该组合物特别适用于治疗高增殖性疾病，如癌症。
• Serine/threonine kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US08697715B2

  公开（公告）日：2014-04-15

  Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  提供了公式I的化合物或其立体异构体、互变异构体、前药或药学上可接受的盐，用于治疗过度增殖、疼痛和炎症性疾病。本文还揭示了使用公式I的化合物或其立体异构体、互变异构体、前药或药学上可接受的盐的方法，用于哺乳动物细胞中的体外、体内和原位诊断、预防或治疗此类疾病或相关病理条件。
• Discovery of (<i>S</i>)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1<i>H</i>-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1<i>H</i>)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development
  作者：James F. Blake、Michael Burkard、Jocelyn Chan、Huifen Chen、Kang-Jye Chou、Dolores Diaz、Danette A. Dudley、John J. Gaudino、Stephen E. Gould、Jonas Grina、Thomas Hunsaker、Lichuan Liu、Matthew Martinson、David Moreno、Lars Mueller、Christine Orr、Patricia Pacheco、Ann Qin、Kevin Rasor、Li Ren、Kirk Robarge、Sheerin Shahidi-Latham、Jeffrey Stults、Francis Sullivan、Weiru Wang、Jianping Yin、Aihe Zhou、Marcia Belvin、Mark Merchant、John Moffat、Jacob B. Schwarz

  DOI：10.1021/acs.jmedchem.6b00389

  日期：2016.6.23

  The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small molecule inhibitor selective for ERK kinase activity.
• US8697715B2
  申请人：——

  公开号：US8697715B2

  公开（公告）日：2014-04-15