4-methyl-5-methoxy-2-phenyl-isothiazol-3(2H)-one | 1133720-37-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methyl-5-methoxy-2-phenyl-isothiazol-3(2H)-one
• 英文别名: 5-methoxy-4-methyl-2-phenyl-1,2-thiazol-3-one
• CAS: 1133720-37-2
• 化学式: C₁₁H₁₁NO₂S
• 分子量: 221.28
• InChiKey: BVDNZBXHYHKKSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-methyl-5-chloro-2-phenyl-isothiazol-3(2H)-one 、 sodium methylate 以 甲醇 为溶剂， 反应 5.0h， 以24%的产率得到4-methyl-5-methoxy-2-phenyl-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

文献信息

• Synthesis of isothiazol-3-one derivatives as inhibitors of histone acetyltransferases (HATs)
  作者：Stephen Gorsuch、Vassilios Bavetsias、Martin G. Rowlands、G. Wynne Aherne、Paul Workman、Michael Jarman、Edward McDonald

  DOI：10.1016/j.bmc.2008.11.079

  日期：2009.1

  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.