| 1133719-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• CAS: 1133719-99-9
• 化学式: C₂₀H₂₂N₂O₃S
• 分子量: 370.472
• InChiKey: GAQDKHRXHLBMJJ-GDNBJRDFSA-N

反应信息

• 作为反应物：
  描述：

  在 三氯乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以10%的产率得到2-(4-morpholinophenyl)-isothiazol-3(2H)-one
  参考文献：
  名称：

  Synthesis of isothiazol-3-one derivatives as inhibitors of histone acetyltransferases (HATs)

  摘要：

  High-throughput screening led to the identification of isothiazolones 1 and 2 as inhibitors of histone acetyltransferase (HAT) with IC50s of 3 mu M and 5 mu M, respectively. Analogues of these hit compounds with variations of the N-phenyl group, and with variety of substituents at C-4, C-5 of the thiazolone ring, were prepared and assayed for inhibition of the HAT enzyme PCAF. Potency is modestly favoured when the N-aryl group is electron deficient (4-pyridyl derivative 10 has IC50 = 1.5 mu M); alkyl substitution at C-4 has little effect, whilst similar substitution at C-5 causes a significant drop in potency. The ring-fused compound 38 has activity (IC50 = 6.1 mu M) to encourage further exploration of this bicyclic structure. The foregoing SAR is consistent with an inhibitory mechanism involving cleavage of the S-N bond of the isothiazolone ring by a catalytically important thiol residue. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.079
• 作为产物：
  描述：

  在 盐酸 、 六氟异丙醇 、 双氧水 作用下， 以 水 为溶剂， 反应 2.0h， 以59%的产率得到
  参考文献：
  名称：

  Synthesis of isothiazol-3-one derivatives as inhibitors of histone acetyltransferases (HATs)

  摘要：

  High-throughput screening led to the identification of isothiazolones 1 and 2 as inhibitors of histone acetyltransferase (HAT) with IC50s of 3 mu M and 5 mu M, respectively. Analogues of these hit compounds with variations of the N-phenyl group, and with variety of substituents at C-4, C-5 of the thiazolone ring, were prepared and assayed for inhibition of the HAT enzyme PCAF. Potency is modestly favoured when the N-aryl group is electron deficient (4-pyridyl derivative 10 has IC50 = 1.5 mu M); alkyl substitution at C-4 has little effect, whilst similar substitution at C-5 causes a significant drop in potency. The ring-fused compound 38 has activity (IC50 = 6.1 mu M) to encourage further exploration of this bicyclic structure. The foregoing SAR is consistent with an inhibitory mechanism involving cleavage of the S-N bond of the isothiazolone ring by a catalytically important thiol residue. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.079