(2-chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)ethylamine | 1173204-22-2

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: (2-chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)ethylamine
• 英文别名: (2-Chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)-ethyl-amine；2-chloro-N-ethyl-6-morpholin-4-yl-5-nitropyrimidin-4-amine
• CAS: 1173204-22-2
• 化学式: C₁₀H₁₄ClN₅O₃
• 分子量: 287.706
• InChiKey: YJBTZZNXBVFUKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)ethylamine 在 一水合肼 作用下， 以 甲醇 为溶剂， 以73%的产率得到2-chloro-N4-ethyl-6-morpholin-4-ylpyrimidine-4,5-diamine
  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：

  4-吗啉代-5-硝基-2,6-二氯嘧啶 、 乙胺 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 以100%的产率得到(2-chloro-6-morpholin-4-yl-5-nitro-pyrimidin-4-yl)ethylamine
  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

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：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。
• 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.