3-(1h-Benzimidazol-2-Yl)-N-[(1-Methyl-3-Phenyl-1h-Pyrazol-5-Yl)carbonyl]-D-Alanine | 1207725-94-7

• 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: 3-(1h-Benzimidazol-2-Yl)-N-[(1-Methyl-3-Phenyl-1h-Pyrazol-5-Yl)carbonyl]-D-Alanine
• 英文别名: (2R)-3-(1H-benzimidazol-2-yl)-2-[(2-methyl-5-phenylpyrazole-3-carbonyl)amino]propanoic acid
• CAS: 1207725-94-7
• 化学式: C₂₁H₁₉N₅O₃
• 分子量: 389.414
• InChiKey: ZNVHZOFBOKBNIL-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl (2R)-3-(1H-1,3-benzodiazol-2-yl)-2-{[(tert-butoxy)carbonyl]amino}propanoate 在 盐酸 、 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 3-(1h-Benzimidazol-2-Yl)-N-[(1-Methyl-3-Phenyl-1h-Pyrazol-5-Yl)carbonyl]-D-Alanine
  参考文献：
  名称：

  Off-Rate Screening (ORS) By Surface Plasmon Resonance. An Efficient Method to Kinetically Sample Hit to Lead Chemical Space from Unpurified Reaction Products

  摘要：

  The dissociation rate constant k(d) (off-rate) is the component of ligand protein binding with the most significant potential to enhance compound potency. Here we provide theoretical and empirical data to show that this parameter can be determined accurately from unpurified reaction products containing designed test compounds. This screening protocol is amenable to parallel chemistry, provides efficiencies of time and materials, and complements existing methodologies for the hit-to-lead phase in fragment-based drug discovery.

  DOI：

  10.1021/jm401848a

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.
• Off-Rate Screening (ORS) By Surface Plasmon Resonance. An Efficient Method to Kinetically Sample Hit to Lead Chemical Space from Unpurified Reaction Products
  作者：James B. Murray、Stephen D. Roughley、Natalia Matassova、Paul A. Brough

  DOI：10.1021/jm401848a

  日期：2014.4.10

  The dissociation rate constant k(d) (off-rate) is the component of ligand protein binding with the most significant potential to enhance compound potency. Here we provide theoretical and empirical data to show that this parameter can be determined accurately from unpurified reaction products containing designed test compounds. This screening protocol is amenable to parallel chemistry, provides efficiencies of time and materials, and complements existing methodologies for the hit-to-lead phase in fragment-based drug discovery.