piperazine-1-carbothioic acid phenethylamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: piperazine-1-carbothioic acid phenethylamide
• 英文别名: N-(2-phenylethyl)piperazine-1-carbothioamide
• 化学式: C₁₃H₁₉N₃S
• 分子量: 249.38
• InChiKey: WJLINFBACPFQMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  59.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  piperazine-1-carbothioic acid phenethylamide 在 sodium hydroxide 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 0.5h， 生成 dimethylcarbamothioic 4-(phenethylcarbamothioyl)piperazine-1-carbothioic thioanhydride
  参考文献：
  名称：

  Substituted carbamothioic amine-1-carbothioic thioanhydrides as novel trichomonicidal fungicides: Design, synthesis, and biology

  摘要：

  Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 mu M and 32.46-735.20 mu M against MTZ-susceptible and-resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50 -240.38 mu M. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.060
• 作为产物：
  描述：

  哌嗪 、 2-苯基乙基异硫代氰酸酯 以 乙醇 为溶剂， 以69%的产率得到piperazine-1-carbothioic acid phenethylamide
  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.
• Substituted carbamothioic amine-1-carbothioic thioanhydrides as novel trichomonicidal fungicides: Design, synthesis, and biology
  作者：Dhanaraju Mandalapu、Bhavana Kushwaha、Sonal Gupta、Shagun Krishna、Nidhi Srivastava、Mahendra Shukla、Pratiksha Singh、Bhavana S. Chauhan、Ravi Goyani、Jagdamba P. Maikhuri、Koneni V. Sashidhara、Brijesh Kumar、Renu Tripathi、Praveen K. Shukla、Mohammad I. Siddiqi、Jawahar Lal、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2017.11.060

  日期：2018.1

  Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 mu M and 32.46-735.20 mu M against MTZ-susceptible and-resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50 -240.38 mu M. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance. (C) 2017 Elsevier Masson SAS. All rights reserved.