(Z)-5-(3,5-dibromo-4-hydroxybenzylidene)-2-(methylsulfanyl)thiazol-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (Z)-5-(3,5-dibromo-4-hydroxybenzylidene)-2-(methylsulfanyl)thiazol-4-one
• 英文别名: (5Z)-5-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-2-methylsulfanyl-1,3-thiazol-4-one
• 化学式: C₁₁H₇Br₂NO₂S₂
• 分子量: 409.122
• InChiKey: PZBMTTMOKQNYTA-YWEYNIOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,7-二氨基庚烷 、 (Z)-5-(3,5-dibromo-4-hydroxybenzylidene)-2-(methylsulfanyl)thiazol-4-one 以 乙醇 为溶剂， 反应 8.0h， 以66%的产率得到(5Z,5'Z)-2,2'-(heptane-1,7-diyldiimino)bis(5-(3,5-dibromo-4-hydroxybenzylidene)-1,3-thiazol-4(5H)-one)
  参考文献：
  名称：

  Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition

  摘要：

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.072
• 作为产物：
  描述：

  3,5-二溴-4-羟基苯甲醛 在 溶剂黄146 、 N,N-二异丙基乙胺 、 β-丙氨酸 作用下， 以 乙醇 为溶剂， 反应 3.5h， 生成 (Z)-5-(3,5-dibromo-4-hydroxybenzylidene)-2-(methylsulfanyl)thiazol-4-one
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Substituted Di-tert-butylphenols as a Novel Class of Potent, Selective, and Orally Active Cyclooxygenase-2 Inhibitors. 1. Thiazolone and Oxazolone Series

  摘要：

  Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and subsequent structure-activity relationship (SAR) studies have identified 4b (PD138387) as the most potent and selective COX-2 inhibitor within the thiazolone and oxazolone series of di-tert-butylphenols. Compound 4b has an IC50 Of 1.7 mu M against recombinant human COX-2 and inhibited COX-2 activity in the J774A.1 cell line with an IC50 of 0.17 mu M. It was inactive against purified ovine COX-1 at 100 mu M and did not inhibit COX-1 activity in platelets at 20 mu M. Compound 4b was also orally active in vivo with an ED40 of 16 mg/kg in the carrageenan footpad edema (CFE) assay and caused no gastrointestinal (GI) damage in rats at the dose of 100 mg/kg but inhibited gastric prostaglandin E-2 (PGE(2)) production in rats' gastric mucosa by 33% following a dose of 100 mg/kg. The SAR studies of this chemical series revealed that the potency and selectivity are very sensitive to minor structural changes. A simple isosteric replacement led to the reversal of selectivity.

  DOI：

  10.1021/jm9805081

文献信息

• Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Substituted Di-<i>tert</i>-butylphenols as a Novel Class of Potent, Selective, and Orally Active Cyclooxygenase-2 Inhibitors. 1. Thiazolone and Oxazolone Series
  作者：Yuntao Song、David T. Connor、Robert Doubleday、Roderick J. Sorenson、Anthony D. Sercel、Paul C. Unangst、Bruce D. Roth、Richard B. Gilbertsen、Kam Chan、Denis J. Schrier、Antonio Guglietta、Dirk A. Bornemeier、Richard D. Dyer

  DOI：10.1021/jm9805081

  日期：1999.4.1

  Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and subsequent structure-activity relationship (SAR) studies have identified 4b (PD138387) as the most potent and selective COX-2 inhibitor within the thiazolone and oxazolone series of di-tert-butylphenols. Compound 4b has an IC50 Of 1.7 mu M against recombinant human COX-2 and inhibited COX-2 activity in the J774A.1 cell line with an IC50 of 0.17 mu M. It was inactive against purified ovine COX-1 at 100 mu M and did not inhibit COX-1 activity in platelets at 20 mu M. Compound 4b was also orally active in vivo with an ED40 of 16 mg/kg in the carrageenan footpad edema (CFE) assay and caused no gastrointestinal (GI) damage in rats at the dose of 100 mg/kg but inhibited gastric prostaglandin E-2 (PGE(2)) production in rats' gastric mucosa by 33% following a dose of 100 mg/kg. The SAR studies of this chemical series revealed that the potency and selectivity are very sensitive to minor structural changes. A simple isosteric replacement led to the reversal of selectivity.
• Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: Effect of dimerisation on phosphatase inhibition
  作者：Manal Sarkis、Diem Ngan Tran、Stéphanie Kolb、Maria A. Miteva、Bruno O. Villoutreix、Christiane Garbay、Emmanuelle Braud

  DOI：10.1016/j.bmcl.2012.10.072

  日期：2012.12

  CDC25 phosphatases are involved in deregulated cell cycle progression and tumor development with poor prognosis. Among the most potent CDC25 inhibitors, quinonoid-based derivatives have been extensively studied. Dimerisation of heterocyclic quinones has led to IRC-083864, a bis-quinone compound with increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were synthesized and assayed for CDC25 inhibitory activity. Most of the dimers displayed enhanced inhibitory activities with micromolar IC50 values lower than that observed for each thiazolone scaffold separately. Moreover, most of these compounds were selective CDC25 inhibitors. Dimer 40 showed an IC50 value of 2.9 mu M and could inhibit CDC25 activity without generating reactive oxygen species which is likely to occur with quinone-based inhibitors. Molecular docking studies suggested that the dimers could bind simultaneously to the active site and the inhibitor binding pocket. (C) 2012 Elsevier Ltd. All rights reserved.