(R)-2-(3-(1H-indol-2-yl)propanamido)-3-(1H-benzo[d]imidazol-2-yl)propanoic acid | 1207725-98-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-(3-(1H-indol-2-yl)propanamido)-3-(1H-benzo[d]imidazol-2-yl)propanoic acid
• 英文别名: (2R)-3-(1H-benzimidazol-2-yl)-2-[3-(1H-indol-2-yl)propanoylamino]propanoic acid
• CAS: 1207725-98-1
• 化学式: C₂₁H₂₀N₄O₃
• 分子量: 376.415
• InChiKey: ZHWBKERXDYLTJJ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl (R)-2-(3-(1H-indol-2-yl)propanamido)-3-(1H-benzo[d]imidazol-2-yl)propanoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-2-(3-(1H-indol-2-yl)propanamido)-3-(1H-benzo[d]imidazol-2-yl)propanoic acid
  参考文献：
  名称：

  Structure-guided design of α-amino acid-derived Pin1 inhibitors

  摘要：

  The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC50 < 100 nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.090

文献信息

• Structure-guided design of α-amino acid-derived Pin1 inhibitors
  作者：Andrew J. Potter、Stuart Ray、Louisa Gueritz、Claire L. Nunns、Christopher J. Bryant、Simon F. Scrace、Natalia Matassova、Lisa Baker、Pawel Dokurno、David A. Robinson、Allan E. Surgenor、Ben Davis、James B. Murray、Christine M. Richardson、Jonathan D. Moore

  DOI：10.1016/j.bmcl.2009.11.090

  日期：2010.1

  The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC50 < 100 nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. (C) 2009 Elsevier Ltd. All rights reserved.