1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)thiourea | 1622931-27-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)thiourea
• 英文别名: [4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)phenyl]thiourea；[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]thiourea
• CAS: 1622931-27-4
• 化学式: C₁₀H₈F₆N₂OS
• 分子量: 318.243
• InChiKey: LRDCZLIACFVMBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.65
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.28
• 氢给体数：
  3.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)thiourea 、 2'-溴-4-氯苯乙酮 以 乙醇 为溶剂， 反应 0.5h， 以77%的产率得到2-(4-(4-(4-chlorophenyl)thiazol-2-ylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol
  参考文献：
  名称：

  Multi-dimensional target profiling of N,4-diaryl-1,3-thiazole-2-amines as potent inhibitors of eicosanoid metabolism

  摘要：

  Eicosanoids like leukotrienes and prostaglandins play a considerable role in inflammation. Produced within the arachidonic acid (AA) cascade, these lipid mediators are involved in the pathogenesis of pain as well as acute and chronic inflammatory diseases like rheumatoid arthritis and asthma. With regard to the lipid cross-talk within the AA pathway, a promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Within this study, thirty N-4-diaryl-1,3-thiazole-2-amine based compounds with different substitution patterns were synthesized and tested in various cell-based assays to investigate their activity and selectivity profile concerning five key enzymes involved in eicosanoid metabolism (5-, 12-, 15-lipoxygenase (LO), cyclooxygenase-1 and -2 (COX-1/-2)). With compound 7, 2-(4-phenyl)thiazol-2-ylamino)phenol (ST-1355), a multi-target ligand targeting all tested enzymes is presented, whereas compound 9, 2-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol (ST-1705), represents a potent and selective 5-LO and COX-2 inhibitor with an IC50 value of 0.9 ± 0.2 μM (5-LO) and a residual activity of 9.1 ± 1.1% at 10 μM (COX-2 product formation). The promising characteristics and the additional non-cytotoxic profile of both compounds reveal new lead structures for the treatment of eicosanoid-mediated diseases.

  DOI：

  10.1016/j.ejmech.2014.07.025
• 作为产物：
  描述：

  N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenylcarbamothioyl)benzamide 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以87%的产率得到1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)thiourea
  参考文献：
  名称：

  Multi-dimensional target profiling of N,4-diaryl-1,3-thiazole-2-amines as potent inhibitors of eicosanoid metabolism

  摘要：

  Eicosanoids like leukotrienes and prostaglandins play a considerable role in inflammation. Produced within the arachidonic acid (AA) cascade, these lipid mediators are involved in the pathogenesis of pain as well as acute and chronic inflammatory diseases like rheumatoid arthritis and asthma. With regard to the lipid cross-talk within the AA pathway, a promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Within this study, thirty N-4-diaryl-1,3-thiazole-2-amine based compounds with different substitution patterns were synthesized and tested in various cell-based assays to investigate their activity and selectivity profile concerning five key enzymes involved in eicosanoid metabolism (5-, 12-, 15-lipoxygenase (LO), cyclooxygenase-1 and -2 (COX-1/-2)). With compound 7, 2-(4-phenyl)thiazol-2-ylamino)phenol (ST-1355), a multi-target ligand targeting all tested enzymes is presented, whereas compound 9, 2-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol (ST-1705), represents a potent and selective 5-LO and COX-2 inhibitor with an IC50 value of 0.9 ± 0.2 μM (5-LO) and a residual activity of 9.1 ± 1.1% at 10 μM (COX-2 product formation). The promising characteristics and the additional non-cytotoxic profile of both compounds reveal new lead structures for the treatment of eicosanoid-mediated diseases.

  DOI：

  10.1016/j.ejmech.2014.07.025

文献信息

• Thiazole derivatives as dual inhibitors of deoxyribonuclease I and 5-lipoxygenase: A promising scaffold for the development of neuroprotective drugs
  作者：Ana Marković、Aleksandra Živković、Mariyana Atanasova、Irini Doytchinova、Bettina Hofmann、Sven George、Simon Kretschmer、Carmen Rödl、Dieter Steinhilber、Holger Stark、Andrija Šmelcerović

  DOI：10.1016/j.cbi.2023.110542

  日期：2023.8

  A library of 43 thiazole derivatives, including 31 previously and 12 newly synthesized in the present study, was evaluated in vitro for their inhibitory properties against bovine pancreatic DNase I. Nine compounds (including three newly synthesized) inhibited the enzyme showing improved inhibitory properties compared to that of the reference crystal violet (IC50 = 346.39 μM). Two compounds (5 and 29)

  在体外评估了 43 种噻唑衍生物的文库，包括 31 种先前合成的和本研究中新合成的 12 种，它们对牛胰腺 DNase I 的抑制特性。九种化合物（包括三种新合成的）抑制酶，与参考结晶紫 (IC 50  = 346.39 μM)。两种化合物（5和29）脱颖而出，成为最有效的 DNase I 抑制剂，IC 50值低于 100 μM。由于这种酶在神经退行性疾病发展中的重要性，还分析了所研究衍生物的 5-LO 抑制特性。化合物（12和29) 被证明是最突出的新型 5-LO 抑制剂，在无细胞试验中， IC 50值分别为 60 nM 和 56 nM。四种化合物，包括先前合成的一种 ( 41 ) 和三种新合成的 ( 12、29和30 )，能够在无细胞中抑制 DNase I，IC 50值低于 200 μM 和 5-LO，IC 50值低于 150 nM化验。分子对接和分子动力学模拟用于阐明分子水平上最有效代表的