2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide | 113104-25-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide
• 英文别名: 2-(7-nitrobenzo[c][1.2.5]oxadiazol-4-yl)thiopyridine-1-oxide；NSC 228155；NSC-228155；NSC228155；7-Nitro-4-(1-oxidopyridin-1-ium-2-yl)sulfanyl-2,1,3-benzoxadiazole
• CAS: 113104-25-9
• 化学式: C₁₁H₆N₄O₄S
• 分子量: 290.259
• InChiKey: ICCFXXDUYSPKOL-UHFFFAOYSA-N

物化性质

• 沸点：
  627.3±65.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO 中≥29 mg/mL；不溶于水；不溶于乙醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  |-20℃|

制备方法与用途

生物活性

NSC 228155 是一种 EGFR 激活剂，能与 EGFR 的胞外区域结合，诱导 EGFR 的磷酸化。此外，它还是一种有效的 KIX-KID 相互作用抑制剂，IC50 值为 0.36 μM，能够抑制 CREB 的激酶诱导结构域 (KID) 和 KIX (KID 相互作用结构域，来自 CBP) 的相互作用。

靶点	IC50 (μM)
EGFR
KIX-KID	0.36

体外研究

NSC 228155 (100 μM) 能通过 SOD1 的作用增强 EGFR 端酪氨酸的磷酸化。

在活的 HEK 293T 细胞中，NSC 228155 (Compound 1) 抑制 CREB-和 VP16-CREB 介导的基因转录，IC50 值分别为 2.09 μM 和 6.14 μM。然而，NSC 228155 并不选择性地抑制 CREB 介导的基因转录。

反应信息

• 作为反应物：
  描述：

  2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide 在 二甲氨基硫代甲酰氯 作用下， 以 乙腈 为溶剂， 以29%的产率得到2-(7-nitrobenzo[c][1.2.5]oxadiazol-4-yl)thiopyridine
  参考文献：
  名称：

  Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription

  摘要：

  Cyclic-AMP response-element binding protein (CREB) is a stimulus-activated transcription factor. Its transcription activity requires its binding with CREB-binding protein (CBP) after CREB is phosphorylated at Ser133. The domains involved for CREB-CBP interaction are kinase-inducible domain (KID) from CREB and KID-interacting domain (KIX) from CBP. Recent studies suggest that CREB is an attractive target for novel cancer therapeutics. To identify novel chemotypes as inhibitors of KIX-KID interaction, we screened the NCI-diversity set of compounds using a split renilla luciferase assay and identified 2-[(7-nitrobenzo[ c][1,2,5]oxadiazol-4-yl)thio] pyridine 1-oxide (compound 1, NSC228155) as a potent inhibitor of KIX-KID interaction. However, compound 1 was not particularly selective against CREB-mediated gene transcription in living HEK 293T cells. Further structure-activityrelationship studies identified 4-aniline substituted nitrobenzofurazans with improved selectivity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.053
• 作为产物：
  描述：

  4-氯-7-硝基苯并-2-氧杂-1,3-二唑 、 2-巯基吡啶-N-氧化物 以 丙酮 为溶剂， 反应 0.17h， 以46%的产率得到2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide
  参考文献：
  名称：

  Bem, Marioara; Radutiu, Ana Cristina; Voicescu, Mariana, Revue Roumaine de Chimie, 2018, vol. 63, # 2, p. 149 - 155

  摘要：

  DOI：

文献信息

• VALDEZ, DAVID;REIER, JOANN C., J. LIQUID CHROMATOGR., 10,(1987) N 10, 2133-2135
  作者：VALDEZ, DAVID、REIER, JOANN C.

  DOI：——

  日期：——
• TREATMENT AND PREVENTION OF DISEASE MEDIATED BY WWP2
  申请人：National University of Singapore

  公开号：EP3983544A1

  公开（公告）日：2022-04-20
• [EN] TREATMENT AND PREVENTION OF DISEASE MEDIATED BY WWP2<br/>[FR] TRAITEMENT ET PRÉVENTION D'UNE MALADIE MÉDIÉE PAR WWP2
  申请人：NAT UNIV SINGAPORE

  公开号：WO2020249710A1

  公开（公告）日：2020-12-17

  Methods of treating and preventing fibrosis and pathological inflammation through inhibition of WWP2 are disclosed, as well as agents for use in such methods.
• Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription
  作者：Fuchun Xie、Bingbing X. Li、Candice Broussard、Xiangshu Xiao

  DOI：10.1016/j.bmcl.2013.07.053

  日期：2013.10

  Cyclic-AMP response-element binding protein (CREB) is a stimulus-activated transcription factor. Its transcription activity requires its binding with CREB-binding protein (CBP) after CREB is phosphorylated at Ser133. The domains involved for CREB-CBP interaction are kinase-inducible domain (KID) from CREB and KID-interacting domain (KIX) from CBP. Recent studies suggest that CREB is an attractive target for novel cancer therapeutics. To identify novel chemotypes as inhibitors of KIX-KID interaction, we screened the NCI-diversity set of compounds using a split renilla luciferase assay and identified 2-[(7-nitrobenzo[ c][1,2,5]oxadiazol-4-yl)thio] pyridine 1-oxide (compound 1, NSC228155) as a potent inhibitor of KIX-KID interaction. However, compound 1 was not particularly selective against CREB-mediated gene transcription in living HEK 293T cells. Further structure-activityrelationship studies identified 4-aniline substituted nitrobenzofurazans with improved selectivity. (C) 2013 Elsevier Ltd. All rights reserved.
• Bem, Marioara; Radutiu, Ana Cristina; Voicescu, Mariana, Revue Roumaine de Chimie, 2018, vol. 63, # 2, p. 149 - 155
  作者：Bem, Marioara、Radutiu, Ana Cristina、Voicescu, Mariana、Caproiu, Miron T.、Draghici, Constantin、Maganu, Maria、Enache, Cristian、Constantinescu, Titus、Balaban, Alexandru T.

  DOI：——

  日期：——