4-(benzylsulfonyl)-7-nitrobenzo[c][1,2,5]oxadiazole | 53619-72-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: 4-(benzylsulfonyl)-7-nitrobenzo[c][1,2,5]oxadiazole
• 英文别名: NSC228148；BI-94；4-Nitro-7-benzylsulphonylbenzofurazan；4-nitro-7-(phenylmethylsulfonyl)-2,1,3-benzoxadiazole；4-(Benzylsulfonyl)-7-(hydroxy(oxido)amino)-2,1,3-benzoxadiazole；4-benzylsulfonyl-7-nitro-2,1,3-benzoxadiazole
• CAS: 53619-72-0
• 化学式: C₁₃H₉N₃O₅S
• 分子量: 319.298
• InChiKey: PVMUCEMCWMKDMP-UHFFFAOYSA-N

物化性质

• 沸点：
  578.4±60.0 °C(Predicted)
• 密度：
  1.541±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(benzylthio)-7-nitrobenzo[c][1,2,5]oxadiazole 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以510 mg的产率得到4-(benzylsulfonyl)-7-nitrobenzo[c][1,2,5]oxadiazole
  参考文献：
  名称：

  Irreversible binding of an anticancer compound (BI-94) to plasma proteins

  摘要：

  1. We investigated the mechanisms responsible for the in vivo instability of a benzofurazan compound BI-94 (NSC228148) with potent anti-cancer activity.2. BI-94 was stable in MeOH, water, and in various buffers at pHs 2.5-5, regardless of the buffer composition. In contrast, BI-94 was unstable in NaOH and at pHs 7-9, regardless of the buffer composition. BI-94 disappeared immediately after spiking into mice, rat, monkey, and human plasma. BI-94 stability in plasma can be only partially restored by acidifying it, which indicated other mechanisms in addition to pH for BI-94 instability in plasma.3. BI-94 formed adducts with the trapping agents, glutathione (GSH) and N-acetylcysteine (NAC), in vivo and in vitro via nucleophilic aromatic substitution reaction. The kinetics of adduct formation showed that neutral or physiological pHs enhanced and accelerated GSH and NAC adduct formation with BI-94, whereas acidic pHs prevented it. Therefore, physiological pHs not only altered BI-94 chemical stability but also enhanced adduct formation with endogenous nucleophiles. In addition, adduct formation with human serum albumin-peptide 3 (HSA-T3) at the Cys34 position was demonstrated.4. In conclusion, BI-94 was unstable at physiological conditions due to chemical instability and irreversible binding to plasma proteins.

  DOI：

  10.3109/00498254.2015.1025250

文献信息

• 2,1,3-BENZOXADIAZOL DERIVATIVES FOR THE INHIBITION OF INFLUENZA A AND B VIRUS AND RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  申请人：Pike Pharma GmbH

  公开号：EP2427442A1

  公开（公告）日：2012-03-14
• METHODS AND COMPOUNDS FOR REGULATING APOPTOSIS
  申请人：Reed John C.

  公开号：US20090118135A1

  公开（公告）日：2009-05-07

  An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.
• GAIN-OF-FUNCTION BCL-2 INHIBITORS
  申请人：HOCKENBERY David

  公开号：US20120252839A1

  公开（公告）日：2012-10-04

  Compounds are described that are useful for treating an apoptosis-associated disease, which are specifically cytotoxic to tumor cells that are overexpressing Bcl-x L , and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x L . Also described is a method for treating an apoptosis-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an active compound that is specifically cytotoxic to tumor cells that are overexpressing Bcl-x L , and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x L . Several scaffolds of active compounds are described.
• COMPOUNDS AND THERAPEUTIC USES
  申请人：Unity Biotechnology, Inc.

  公开号：US20170281649A1

  公开（公告）日：2017-10-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.
• US8865901B2
  申请人：——

  公开号：US8865901B2

  公开（公告）日：2014-10-21