benzyl 4-(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)piperazine-1-carbothioamide

• 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: benzyl 4-(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)piperazine-1-carbothioamide
• 英文别名: N-benzyl-4-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]piperazine-1-carbothioamide
• 化学式: C₂₈H₃₀F₃N₃OS
• 分子量: 513.627
• InChiKey: CBCUBJDIPGSPNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  piperazine-1-carbothioic acid benzylamide 在 sodium tetrahydroborate 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 benzyl 4-(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)piperazine-1-carbothioamide
  参考文献：
  名称：

  N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual-action vaginal microbicides with reverse transcriptase inhibition

  摘要：

  The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-l-carbothioamide (12-26) derivatives as topical vaginal microbicides which were evaluated for anti-Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line (HeLa) and the vaginal flora, Lactobacillus. Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti-Trithomonas (MIC 46.72 mu M) and antifimgal (MIC 9.34 -74.8 mu M) activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy (22) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ-rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.07.021

文献信息

• N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual-action vaginal microbicides with reverse transcriptase inhibition
  作者：Veenu Bala、Dhanaraju Mandalapu、Sonal Gupta、Santosh Jangir、Bhavana Kushwaha、Yashpal S. Chhonker、Hardik Chandasana、Shagun Krishna、Kavita Rawat、Atul Krishna、Mala Singh、Satya N. Sankhwar、Praveen K. Shukla、Jagdamba P. Maikhuri、Rabi S. Bhatta、Mohammad I. Siddiqi、Rajkamal Tripathi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2015.07.021

  日期：2015.8

  The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-l-carbothioamide (12-26) derivatives as topical vaginal microbicides which were evaluated for anti-Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line (HeLa) and the vaginal flora, Lactobacillus. Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti-Trithomonas (MIC 46.72 mu M) and antifimgal (MIC 9.34 -74.8 mu M) activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy (22) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ-rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9. (C) 2015 Elsevier Masson SAS. All rights reserved.