5-(tert-butyl)-3-(4-chloro-2-fluoro-5-nitrophenyl)-1,3,4-thiadiazol-2(3H)-one | 1355505-58-6

• 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: 5-(tert-butyl)-3-(4-chloro-2-fluoro-5-nitrophenyl)-1,3,4-thiadiazol-2(3H)-one
• CAS: 1355505-58-6
• 化学式: C₁₂H₁₁ClFN₃O₃S
• 分子量: 331.755
• InChiKey: BHXNBWDRHBVFQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.03
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-(tert-butyl)-3-(4-chloro-2-fluoro-5-nitrophenyl)-1,3,4-thiadiazol-2(3H)-one 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成
  参考文献：
  名称：

  Quantitative structure–activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-ones as human protoporphyrinogen oxidase inhibitors

  摘要：

  Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has attracted great interest during the last decades due to its unique biochemical characteristics and biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, 23 new 1,3,4-thiadiazol-2(3H)-ones bearing benzothiazole substructure were designed and synthesized. The in vitro assay indicated that the newly synthesized compounds 1a-w displayed good inhibition activity against human PPO (hPPO) with K-i values ranging from 0.04 mu M to 245 mu M. To the knowledge, compound 1a, O-ethyl S-(5-(5-(tert-butyl)-2-oxo-1,3,4-thiadiazol-3(2H)-yl)-6-fluorobenzothiazol-2-yl)carbonothioate, with the K-i value of 40 nM, is so far known as the most potent inhibitor against hPPO. Based on the molecular docking and modified molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) calculations, the quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-one derivatives were established with excellent correlation relationships (r(2) = 0.81) between the calculated and experimental binding free energies. Some important insights were also concluded for guiding the future rational design of new hPPO inhibitors with improved potency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.079
• 作为产物：
  描述：

  5-(tert-butyl)-3-(4-chloro-2-fluorophenyl)-1,3,4-thiadiazol-2(3H)-one 在 硫酸 、 硝酸 作用下， 反应 3.25h， 以64%的产率得到5-(tert-butyl)-3-(4-chloro-2-fluoro-5-nitrophenyl)-1,3,4-thiadiazol-2(3H)-one
  参考文献：
  名称：

  Quantitative structure–activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-ones as human protoporphyrinogen oxidase inhibitors

  摘要：

  Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has attracted great interest during the last decades due to its unique biochemical characteristics and biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, 23 new 1,3,4-thiadiazol-2(3H)-ones bearing benzothiazole substructure were designed and synthesized. The in vitro assay indicated that the newly synthesized compounds 1a-w displayed good inhibition activity against human PPO (hPPO) with K-i values ranging from 0.04 mu M to 245 mu M. To the knowledge, compound 1a, O-ethyl S-(5-(5-(tert-butyl)-2-oxo-1,3,4-thiadiazol-3(2H)-yl)-6-fluorobenzothiazol-2-yl)carbonothioate, with the K-i value of 40 nM, is so far known as the most potent inhibitor against hPPO. Based on the molecular docking and modified molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) calculations, the quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-one derivatives were established with excellent correlation relationships (r(2) = 0.81) between the calculated and experimental binding free energies. Some important insights were also concluded for guiding the future rational design of new hPPO inhibitors with improved potency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.079