1-(4-fluorophenyl)-3-[1-(4-nitro-2-trifluoromethylphenyl)piperidin-4-ylamino]propan-1-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-fluorophenyl)-3-[1-(4-nitro-2-trifluoromethylphenyl)piperidin-4-ylamino]propan-1-ol
• 英文别名: alsinol；1-(4-Fluoro-phenyl)-3-[1-(4-nitro-2-trifluoromethyl-phenyl)-piperidin-4-ylamino]-propan-1-ol；1-(4-fluorophenyl)-3-[[1-[4-nitro-2-(trifluoromethyl)phenyl]piperidin-4-yl]amino]propan-1-ol
• 化学式: C₂₁H₂₃F₄N₃O₃
• 分子量: 441.426
• InChiKey: ARJGEKJZVHJDFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81.3
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氟-5-硝基三氟甲苯 在 盐酸 、 sodium tetrahydroborate 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 1-(4-fluorophenyl)-3-[1-(4-nitro-2-trifluoromethylphenyl)piperidin-4-ylamino]propan-1-ol
  参考文献：
  名称：

  Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes

  摘要：

  Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested againstPlasmodium,Babesia,Trypanosoma, andLeishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity againstPlasmodium falciparumand was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds againstBabesia divergens, and against promastigotes, and amastigotes stages ofLeishmaniain vitro. It inhibited the in vitro growth of two African animal strains ofTrypanosomabut was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.

  DOI：

  10.1007/s00436-020-06832-y

文献信息

• US9688633B2
  申请人：——

  公开号：US9688633B2

  公开（公告）日：2017-06-27
• [EN] NEW ARYLAMINOALCOHOL DERIVATIVES WITH ANTIPLASMODIAL ACTIVITY<br/>[FR] NOUVEAUX DÉRIVÉS ARYL-AMINO-ALCOOL À ACTIVITÉ ANTIPLASMODIQUE
  申请人：INST RECH DEVELOPPEMENT IRD

  公开号：WO2014140671A1

  公开（公告）日：2014-09-18

  The present invention relates to new arylaminoalcohol derivatives of formula (I), and to a method for the preparation of such compounds: The invention also relates to the use of these compounds as medicaments, and in particular for the prevention and/or the treatment of parasitic diseases caused by apicomplexan parasites such as malaria and toxoplasmosis. Finally, the invention relates to pharmaceutical compositions containing such compounds of formula (I) as active principles.
• Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes
  作者：Maria H Arias、Miguel Quiliano、Sandra Bourgeade-Delmas、Isabelle Fabing、Isabelle Chantal、David Berthier、Cécile Minet、Veronique Eparvier、Jonathan Sorres、Didier Stien、Silvia Galiano、Ignacio Aldana、Alexis Valentin、Giovanny Garavito、Eric Deharo

  DOI：10.1007/s00436-020-06832-y

  日期：2020.10

  Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested againstPlasmodium,Babesia,Trypanosoma, andLeishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity againstPlasmodium falciparumand was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds againstBabesia divergens, and against promastigotes, and amastigotes stages ofLeishmaniain vitro. It inhibited the in vitro growth of two African animal strains ofTrypanosomabut was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.