Tert-butyl 4-[2-methyl-5-(phenylcarbamoyl)-3-(2-pyrrolidin-1-ylethylamino)phenyl]piperazine-1-carboxylate | 871340-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Tert-butyl 4-[2-methyl-5-(phenylcarbamoyl)-3-(2-pyrrolidin-1-ylethylamino)phenyl]piperazine-1-carboxylate
• CAS: 871340-92-0
• 化学式: C₂₉H₄₁N₅O₃
• 分子量: 507.676
• InChiKey: XBQOFHFBVGNBGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[2-methyl-5-(phenylcarbamoyl)-3-(2-pyrrolidin-1-ylethylamino)phenyl]piperazine-1-carboxylate 在 盐酸 、 甲醇 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.03h， 生成
  参考文献：
  名称：

  Pyrazolopyrimidines as dual Akt/p70S6K inhibitors

  摘要：

  Activation of the PI3K/Akt/mTOR kinase pathway is frequently associated with human cancer. Selective inhibition of p70S6Kinase, which is the last kinase in the PI3K pathway, is not sufficient for strong tumor growth inhibition and can lead to activation of upstream proteins including Akt through relief of a negative feedback loop. Targeting multiple sites in the PI3K pathway might be beneficial for optimal activity. In this manuscript we report the design of dual Akt/p70S6K inhibitors and the evaluation of the lead compound 11b in vivo, which was eventually advanced into clinical development. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.011
• 作为产物：
  描述：

  3,5-二溴-4-甲基苯甲酸甲酯 在 N-甲基吗啉 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-羟基-7-氮杂苯并三氮唑 、 水 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 potassium hydroxide 、 sodium t-butanolate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.0h， 生成 Tert-butyl 4-[2-methyl-5-(phenylcarbamoyl)-3-(2-pyrrolidin-1-ylethylamino)phenyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Pyrazolopyrimidines as dual Akt/p70S6K inhibitors

  摘要：

  Activation of the PI3K/Akt/mTOR kinase pathway is frequently associated with human cancer. Selective inhibition of p70S6Kinase, which is the last kinase in the PI3K pathway, is not sufficient for strong tumor growth inhibition and can lead to activation of upstream proteins including Akt through relief of a negative feedback loop. Targeting multiple sites in the PI3K pathway might be beneficial for optimal activity. In this manuscript we report the design of dual Akt/p70S6K inhibitors and the evaluation of the lead compound 11b in vivo, which was eventually advanced into clinical development. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.011

文献信息

• KINASE MODULATORS AND METHODS OF USE
  申请人：Exelixis, Inc.

  公开号：EP1750727A2

  公开（公告）日：2007-02-14
• Kinase Modulators and Methods of Use
  申请人：Anand Neel K.

  公开号：US20080076774A1

  公开（公告）日：2008-03-27

  The present invention relates to compounds of the Formula (I) and (II) wherein R, R 21 , R 25 -R 33 , m, n, X 21 -X 23 , and Q 1 are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly p70S6 and/or Akt kinases. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.
• US8076338B2
  申请人：——

  公开号：US8076338B2

  公开（公告）日：2011-12-13
• [EN] KINASE MODULATORS AND METHODS OF USE<br/>[FR] MODULATEURS DES PROTEINES KINASES ET LEURS METHODES D'UTILISATION
  申请人：EXELIXIS INC

  公开号：WO2005117909A2

  公开（公告）日：2005-12-15

  The present invention relates to compounds of the Formula (I) and (II) wherein R, R21, R25-R33, m, n, X21-X23, and Q1 are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly p70S6 and/or Akt kinases. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.
• Pyrazolopyrimidines as dual Akt/p70S6K inhibitors
  作者：Kenneth D. Rice、Moon H. Kim、Joerg Bussenius、Neel K. Anand、Charles M. Blazey、Owen J. Bowles、Lynne Canne-Bannen、Diva S.-M. Chan、Baili Chen、Erick W. Co、Simona Costanzo、Steven C. DeFina、Larisa Dubenko、Stefan Engst、Maurizio Franzini、Ping Huang、Vasu Jammalamadaka、Richard G. Khoury、Rhett R. Klein、A.Douglas Laird、Donna T. Le、Morrison B. Mac、David J. Matthews、David Markby、Nicole Miller、John M. Nuss、Jason J. Parks、Tsze H. Tsang、Amy L. Tsuhako、Yong Wang、Wei Xu

  DOI：10.1016/j.bmcl.2012.03.011

  日期：2012.4

  Activation of the PI3K/Akt/mTOR kinase pathway is frequently associated with human cancer. Selective inhibition of p70S6Kinase, which is the last kinase in the PI3K pathway, is not sufficient for strong tumor growth inhibition and can lead to activation of upstream proteins including Akt through relief of a negative feedback loop. Targeting multiple sites in the PI3K pathway might be beneficial for optimal activity. In this manuscript we report the design of dual Akt/p70S6K inhibitors and the evaluation of the lead compound 11b in vivo, which was eventually advanced into clinical development. (C) 2012 Elsevier Ltd. All rights reserved.