4-[2-(N,N'-bis-tert-butoxycarbonylguanidino)-ethylamino]benzoic acid | 936571-56-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[2-(N,N'-bis-tert-butoxycarbonylguanidino)-ethylamino]benzoic acid
• 英文别名: N,N'-bis-tert-butoxycarbonyl-4-(2-guanidinoethylamino)benzoic acid
• CAS: 936571-56-1
• 化学式: C₂₀H₃₀N₄O₆
• 分子量: 422.481
• InChiKey: DKPKPNPHVMGRDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  138.35
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-[2-(N,N'-bis-tert-butoxycarbonylguanidino)-ethylamino]benzoic acid 、 alkaline earth salt of/the/ methylsulfuric acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三异丙基硅烷 、 茴香硫醚 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 12.25h， 以97%的产率得到2(S)-{2(S)-[4-(2-guanidino-ethylamino)benzoylamino]-3-methyl-butyrylamino}-3-phenyl-propionic acid
  参考文献：
  名称：

  Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

  摘要：

  Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3 beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.004
• 作为产物：
  描述：

  N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine 、 4-(2-amino-ethylamino)benzoic acid 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以61%的产率得到4-[2-(N,N'-bis-tert-butoxycarbonylguanidino)-ethylamino]benzoic acid
  参考文献：
  名称：

  Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

  摘要：

  Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3 beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.004

文献信息

• Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents
  作者：Katherine J. Kayser-Bricker、Matthew P. Glenn、Sang Hoon Lee、Said M. Sebti、Jin Q. Cheng、Andrew D. Hamilton

  DOI：10.1016/j.bmc.2008.09.058

  日期：2009.2

  Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket. In this paper we present the development of high affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3 beta substrate sequence. Optimization of initial peptidic leads resulted in the development of several classes of small molecule inhibitors, which have comparable potency to the initial peptidomimetics, while eliminating the remaining amino acid residues. We have identified the first non-peptidic substrate-mimetic lead inhibitors of Akt 29a-b, which have affinities of 17 and 12 mu M, respectively. This strategy has potential to provide a useful set of molecular probes to assist in the validation of Akt as a potential target for anti-cancer drug design. (C) 2009 Published by Elsevier Ltd.
• WO2008/70823
  申请人：——

  公开号：——

  公开（公告）日：——