{[4-(5-amino-1H-indol-2-yl)phenylcarbamoyl]methyl}carbamic acid tert-butyl ester | 1032374-39-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {[4-(5-amino-1H-indol-2-yl)phenylcarbamoyl]methyl}carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[2-[4-(5-amino-1H-indol-2-yl)anilino]-2-oxoethyl]carbamate
• CAS: 1032374-39-2
• 化学式: C₂₁H₂₄N₄O₃
• 分子量: 380.447
• InChiKey: JUHJPQCMLLNFIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {[4-(5-amino-1H-indol-2-yl)phenylcarbamoyl]methyl}carbamic acid tert-butyl ester 、 对氰基溴化苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以78%的产率得到[(4-{5-[bis(4-cyanobenzyl)amino]-1H-indol-2-yl}phenylcarbamoyl)methyl]carbamic acid tert-butyl ester
  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：

  {[4-(5-nitro-1H-indol-2-yl)phenylcarbamoyl]methyl}carbamic acid tert-butyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 以92%的产率得到{[4-(5-amino-1H-indol-2-yl)phenylcarbamoyl]methyl}carbamic acid tert-butyl ester
  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：——
• US8822524B2
  申请人：——

  公开号：US8822524B2

  公开（公告）日：2014-09-02
• 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.