5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine | 1173204-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine
• 英文别名: 4-(5-chloro-3-ethyltriazolo[4,5-d]pyrimidin-7-yl)morpholine
• CAS: 1173204-21-1
• 化学式: C₁₀H₁₃ClN₆O
• 分子量: 268.706
• InChiKey: ASSCJONSBSHJNW-UHFFFAOYSA-N

物化性质

• 熔点：
  168 °C
• 沸点：
  439.5±45.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  69
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine 、 4-氨基苯硼酸频哪醇酯 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.75h， 以92%的产率得到4-(3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenylamine
  参考文献：
  名称：

  Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402

  摘要：

  Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3K alpha and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating Suppression of PI3K/mTOR signaling as a potential anticancer therapy.

  DOI：

  10.1021/jm9014982
• 作为产物：
  描述：

  2-chloro-N4-ethyl-6-morpholin-4-ylpyrimidine-4,5-diamine 在 sodium nitrite 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 2.0h， 以76%的产率得到5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine
  参考文献：
  名称：

  Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402

  摘要：

  Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3K alpha and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating Suppression of PI3K/mTOR signaling as a potential anticancer therapy.

  DOI：

  10.1021/jm9014982
• 作为试剂：
  描述：

  (2-chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)ethylamine 、 sodium nitrite 在 5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine 作用下， 以to give the final product (250 mg, 64% yield)的产率得到5-chloro-3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine
  参考文献：
  名称：

  3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  本发明涉及式1的3H-[1,2,3]三唑并[4,5-d]嘧啶化合物或其药学上可接受的盐，其中构成变量如本文所定义，以及包含该化合物的组合物和制备和使用该化合物的方法。

  公开号：

  US20090181963A1

文献信息

• 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Wyeth LLC

  公开号：EP2252296A1

  公开（公告）日：2010-11-24
• [EN] 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES<br/>[FR] COMPOSÉS DE 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE, UTILISATIONS DE CEUX-CI EN TANT QU'INHIBITEURS DE LA MTOR KINASE ET DE LA PI3 KINASE, ET SYNTHÈSES DE CEUX-CI
  申请人：WYETH CORP

  公开号：WO2009091788A1

  公开（公告）日：2009-07-23

  The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1 or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
• Lead Optimization of N-3-Substituted 7-Morpholinotriazolopyrimidines as Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of PKI-402
  作者：Christoph M. Dehnhardt、Aranapakam M. Venkatesan、Efren Delos Santos、Zecheng Chen、Osvaldo Santos、Semiramis Ayral-Kaloustian、Natasja Brooijmans、Robert Mallon、Irwin Hollander、Larry Feldberg、Judy Lucas、Inder Chaudhary、Ker Yu、Jay Gibbons、Robert Abraham、Tarek S. Mansour

  DOI：10.1021/jm9014982

  日期：2010.1.28

  Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3K alpha and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating Suppression of PI3K/mTOR signaling as a potential anticancer therapy.
• 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Dehnhardt Christoph Martin

  公开号：US20090181963A1

  公开（公告）日：2009-07-16

  The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  这项发明涉及Formula 1中的3H-[1,2,3]三唑并[4,5-d]嘧啶化合物或其药用可接受的盐，其中构成变量如本文所定义，包括这些化合物的组合物，以及制备和使用这些化合物的方法。