3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-D]pyrimidin-2-YL)-N-[2-(2-(hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide

• 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: 3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-D]pyrimidin-2-YL)-N-[2-(2-(hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide
• 英文别名: 3-(5-amino-7-oxo-6H-triazolo[4,5-d]pyrimidin-2-yl)-N-[[2-[2-(hydroxymethyl)phenyl]sulfanylphenyl]methyl]benzamide
• 化学式: C₂₅H₂₁N₇O₃S
• 分子量: 499.553
• InChiKey: IXDQOBDHBWEZOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  间氨基苯甲酸 在 吡啶 、 tetrafluoroboric acid 、 水 、 sodium acetate 、 copper(II) sulfate 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 亚硝酸异戊酯 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 生成 3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-D]pyrimidin-2-YL)-N-[2-(2-(hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide
  参考文献：
  名称：

  Discovery of Potent Inhibitors of Dihydroneopterin Aldolase Using CrystaLEAD High-Throughput X-ray Crystallographic Screening and Structure-Directed Lead Optimization

  摘要：

  Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC50 values of about 1 muM against DHNA were identified, and crystal structures of their enzyme-bound complex's were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC50 values.

  DOI：

  10.1021/jm030497y

文献信息

• Discovery of Potent Inhibitors of Dihydroneopterin Aldolase Using CrystaLEAD High-Throughput X-ray Crystallographic Screening and Structure-Directed Lead Optimization
  作者：William J. Sanders、Vicki L. Nienaber、Claude G. Lerner、J. Owen McCall、Sean M. Merrick、Susan J. Swanson、John E. Harlan、Vincent S. Stoll、Geoffrey F. Stamper、Stephen F. Betz、Kevin R. Condroski、Robert P. Meadows、Jean M. Severin、Karl A. Walter、Peter Magdalinos、Clarissa G. Jakob、Rolf Wagner、Bruce A. Beutel

  DOI：10.1021/jm030497y

  日期：2004.3.1

  Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC50 values of about 1 muM against DHNA were identified, and crystal structures of their enzyme-bound complex's were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC50 values.