(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-ethyl-3-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one | 1453849-92-7

• 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-ethyl-3-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
• 英文别名: 1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(2-ethyl-5-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one
• CAS: 1453849-92-7
• 化学式: C₂₃H₂₂ClFN₆O₂
• 分子量: 468.918
• InChiKey: GHZDYDZCPLVBIW-HXUWFJFHSA-N

物化性质

• 沸点：
  732.0±70.0 °C(predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 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：

  在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.25h， 生成 (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-ethyl-3-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.6b00389

文献信息

• [EN] SERINE/THREONINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA SÉRINE / THRÉONINE KINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2013130976A1

  公开（公告）日：2013-09-06

  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。
• 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。
• US8697715B2
  申请人：——

  公开号：US8697715B2

  公开（公告）日：2014-04-15
• US9259470B2
  申请人：——

  公开号：US9259470B2

  公开（公告）日：2016-02-16
• US9708290B2
  申请人：——

  公开号：US9708290B2

  公开（公告）日：2017-07-18