4-amino-N-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzamide | 1032373-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-amino-N-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzamide
• CAS: 1032373-52-6
• 化学式: C₂₉H₂₄N₄O₃
• 分子量: 476.535
• InChiKey: IEJJQUWPXFIFCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  99.12
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-amino-N-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzamide 、 N2-乙酰基-N5-[[[(3,4-二氢-2,2,5,7,8-五甲基-2H-1-苯并吡喃-6-基)磺酰基]氨基]亚氨基甲基]-L-鸟氨酸 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.09.058
• 作为产物：
  描述：

  N-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)-4-nitrobenzamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、241.32 kPa 条件下， 反应 2.0h， 以86%的产率得到4-amino-N-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzamide
  参考文献：
  名称：

  Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.09.058

文献信息

• WO2008/70823
  申请人：——

  公开号：——

  公开（公告）日：——