8-[2-[[(1R,3S,4S)-3-fluoro-4-hydroxycyclopentyl]amino]pyrimidin-4-yl]-2-[(1S)-2-hydroxy-1-phenylethyl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 8-[2-[[(1R,3S,4S)-3-fluoro-4-hydroxycyclopentyl]amino]pyrimidin-4-yl]-2-[(1S)-2-hydroxy-1-phenylethyl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one
• 化学式: C₂₅H₂₈FN₅O₃
• 分子量: 465.527
• InChiKey: BRNXJJBPGRMYLF-LBVMUVSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-2-(2-hydroxy-1-phenylethyl)-8-(2-(methylthio)pyrimidin-4-yl)-2,3,4,5-tetrahydro-1H-pyrrolo-[1,2-a][1,4]diazepin-1-one 在 Oxone 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.83h， 生成 8-[2-[[(1R,3S,4S)-3-fluoro-4-hydroxycyclopentyl]amino]pyrimidin-4-yl]-2-[(1S)-2-hydroxy-1-phenylethyl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one
  参考文献：
  名称：

  Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase

  摘要：

  A series of structure based drug design hypotheses and focused screening efforts led to the identification of tetrahydropyrrolo-diazepenones with striking potency against ERK2 kinase. The role of fluorination in mitigating microsomal clearance was systematically explored. Ultimately, it was found that fluorination of a cyclopentanol substructure provided significant improvement in both potency and human metabolic stability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.091

文献信息

• TREATMENT OF SQUAMOUS CELL CARCINOMAS WITH INHIBITORS OF ERK
  申请人：Kura Oncology, Inc.

  公开号：US20190192517A1

  公开（公告）日：2019-06-27

  The present disclosure provides methods and systems for identifying and/or treating subjects having cancer, such as squamous cell carcinoma, who are more likely to respond to treatment with an ERK inhibitor.
• [EN] TREATMENT OF ADENOCARCINOMAS WITH MAPK PATHWAY INHIBITORS<br/>[FR] TRAITEMENT D'ADÉNOCARCINOMES AVEC DES INHIBITEURS DE LA VOIE MAPK
  申请人：KURA ONCOLOGY INC

  公开号：WO2020046966A1

  公开（公告）日：2020-03-05

  The present disclosure provides methods and systems for identifying and/or treating subjects having cancer, such as adenocarcinoma, who are more likely to respond to treatment with a MAPK pathway inhibitor.