butyl N-[(2S)-1-[[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]carbamate | 1428427-64-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: butyl N-[(2S)-1-[[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1428427-64-8
• 化学式: C₁₉H₂₆FN₃O₃S
• 分子量: 395.498
• InChiKey: MEFRFYXPBNKFGY-WBMJQRKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  氯甲酸丁酯 在 N,N-二甲基苄胺 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 7.5h， 生成 butyl N-[(2S)-1-[[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors

  摘要：

  A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, H-1, C-13 and F-19 NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.052

文献信息

• Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors
  作者：Aleš Imramovský、Vladimír Pejchal、Šárka Štěpánková、Katarína Vorčáková、Josef Jampílek、Ján Vančo、Petr Šimůnek、Karel Královec、Lenka Brůčková、Jana Mandíková、František Trejtnar

  DOI：10.1016/j.bmc.2013.01.052

  日期：2013.4

  A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, H-1, C-13 and F-19 NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound. (C) 2013 Elsevier Ltd. All rights reserved.