1-[4-[7-cyclopentyl-4-[(3S)-3-methylmorpholin-4-yl]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea | 1207367-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 1-[4-[7-cyclopentyl-4-[(3S)-3-methylmorpholin-4-yl]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea
• CAS: 1207367-21-2
• 化学式: C₂₆H₃₆N₆O₂
• 分子量: 464.611
• InChiKey: DVGJQKJHFIBNOB-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  82.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea 、 环戊酮 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 1-[4-[7-cyclopentyl-4-[(3S)-3-methylmorpholin-4-yl]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea
  参考文献：
  名称：

  Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

  摘要：

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.

  DOI：

  10.1021/ml3003132

文献信息

• PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：EP2318377B1

  公开（公告）日：2013-08-21
• US8163763B2
  申请人：——

  公开号：US8163763B2

  公开（公告）日：2012-04-24
• Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349
  作者：Zhonghua Pei、Elizabeth Blackwood、Lichuan Liu、Shiva Malek、Marcia Belvin、Michael F. T. Koehler、Daniel F. Ortwine、Huifen Chen、Frederick Cohen、Jane R. Kenny、Philippe Bergeron、Kevin Lau、Cuong Ly、Xianrui Zhao、Anthony A. Estrada、Tom Truong、Jennifer A. Epler、Jim Nonomiya、Lan Trinh、Steve Sideris、John Lesnick、Linda Bao、Ulka Vijapurkar、Sophie Mukadam、Suzanne Tay、Gauri Deshmukh、Yung-Hsiang Chen、Xiao Ding、Lori S. Friedman、Joseph P. Lyssikatos

  DOI：10.1021/ml3003132

  日期：2013.1.10

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.