4-((9H-purin-6-yl)thio)-7-bromo-5-nitrobenzo[c][1,2,5]thiadiazole

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-((9H-purin-6-yl)thio)-7-bromo-5-nitrobenzo[c][1,2,5]thiadiazole
• 英文别名: 6-[(7-bromo-5-nitro-2,1,3-benzothiadiazol-4-yl)sulfanyl]-9H-purine；7-bromo-5-nitro-4-(7H-purin-6-ylsulfanyl)-2,1,3-benzothiadiazole
• 化学式: C₁₁H₄BrN₇O₂S₂
• mdl: MFCD03216811
• 分子量: 410.234
• InChiKey: BICNRUFKCWJSQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  180
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 4-((9H-purin-6-yl)thio)-7-bromo-5-nitrobenzo[c][1,2,5]thiadiazole 以 乙腈 为溶剂， 反应 0.08h， 生成 N⁵-((R)-3-((7-bromo-5-nitrobenzo[c][1,2,5]thiadiazol-4-yl)thio)-1-((carboxymethyl)amino)-1-oxopropan-2-yl)-L-glutamine
  参考文献：
  名称：

  PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS

  摘要：

  Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter.

  DOI：

  10.1021/jm5019093