Tert-butyl 4-[5-(4-chloro-2-hydroxy-phenoxy)thiophene-2-carbonyl]piperazine-1-carboxylate | 1428627-06-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Tert-butyl 4-[5-(4-chloro-2-hydroxy-phenoxy)thiophene-2-carbonyl]piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[5-(4-chloro-2-hydroxyphenoxy)thiophene-2-carbonyl]piperazine-1-carboxylate
• CAS: 1428627-06-8
• 化学式: C₂₀H₂₃ClN₂O₅S
• 分子量: 438.932
• InChiKey: SCLMNRGNCLBCLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[5-(4-chloro-2-hydroxy-phenoxy)thiophene-2-carbonyl]piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到[5-(4-Chloro-2-hydroxy-phenoxy)-2-thienyl]-piperazin-1-yl-methanone
  参考文献：
  名称：

  Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase

  摘要：

  Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.019
• 作为产物：
  描述：

  5-溴噻吩-2-甲醛 在 sodium chlorite 、 potassium dihydrogenphosphate 、 三溴化硼 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 68.0h， 生成 Tert-butyl 4-[5-(4-chloro-2-hydroxy-phenoxy)thiophene-2-carbonyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase

  摘要：

  Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.019

文献信息

• Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase
  作者：Gang Cheng、Stephen P. Muench、Ying Zhou、Gustavo A. Afanador、Ernest J. Mui、Alina Fomovska、Bo Shiun Lai、Sean T. Prigge、Stuart Woods、Craig W. Roberts、Mark R. Hickman、Patty J. Lee、Susan E. Leed、Jennifer M. Auschwitz、David W. Rice、Rima McLeod

  DOI：10.1016/j.bmcl.2013.02.019

  日期：2013.4

  Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130. (C) 2013 Elsevier Ltd. All rights reserved.