1-((2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio)carbonothioyl)piperidin-4-yl-2-(piperidin-1-yl)acetate | 1353898-30-2

• 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: 1-((2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio)carbonothioyl)piperidin-4-yl-2-(piperidin-1-yl)acetate
• 英文别名: [1-[2-(2-Methyl-5-nitroimidazol-1-yl)ethylsulfanylcarbothioyl]piperidin-4-yl] 2-piperidin-1-ylacetate
• CAS: 1353898-30-2
• 化学式: C₁₉H₂₉N₅O₄S₂
• 分子量: 455.602
• InChiKey: HFQVDDJNXKLYQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  154
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  甲硝唑 在 咪唑 、 sodium tetrahydroborate 、 碘 、 sodium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 8.08h， 生成 1-((2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio)carbonothioyl)piperidin-4-yl-2-(piperidin-1-yl)acetate
  参考文献：
  名称：

  Potentiating Metronidazole Scaffold against Resistant Trichomonas: Design, Synthesis, Biology and 3D–QSAR Analysis

  摘要：

  Metronidazole (MTZ), the FDA-approved drug against Trichomonas vaginalis (TV), is being challenged seriously by drug resistance, while its inertness to sperm makes it ineffective as a vaginal contraceptive. Thirteen piperidine dithiocarbamate hybrids of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethane (8-20) were designed to potentiate the MTZ framework against drug resistance and sperm. New compounds were 1.2-12.1 times more effective against MTZ-susceptible and -resistant strains of TV. All of the compounds exhibited high safety toward cervical (HeLa) cells and Lactobacillus. Thirty-eight compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure activity relationship. Good predictive r(pred)(2) values for CoMFA and CoMSIA models reflected the robustness of the predictive ability. This was validated by designing five new analogues (46-50), which were potently microbicidal (3-10 and 10-20 times against MTZ-susceptible and -resistant TV, respectively) and spermicidal. This in vitro study may have significant clinical relevance, which could become evident in due course.

  DOI：

  10.1021/ml200161t

文献信息

• Potentiating Metronidazole Scaffold against Resistant Trichomonas: Design, Synthesis, Biology and 3D–QSAR Analysis
  作者：Lalit Kumar、Ashish Jain、Nand Lal、Amit Sarswat、Santosh Jangir、Lokesh Kumar、Vishal Singh、Priyanka Shah、Swatantra K. Jain、Jagdamba P. Maikhuri、Mohammad I. Siddiqi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1021/ml200161t

  日期：2012.2.9

  Metronidazole (MTZ), the FDA-approved drug against Trichomonas vaginalis (TV), is being challenged seriously by drug resistance, while its inertness to sperm makes it ineffective as a vaginal contraceptive. Thirteen piperidine dithiocarbamate hybrids of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethane (8-20) were designed to potentiate the MTZ framework against drug resistance and sperm. New compounds were 1.2-12.1 times more effective against MTZ-susceptible and -resistant strains of TV. All of the compounds exhibited high safety toward cervical (HeLa) cells and Lactobacillus. Thirty-eight compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure activity relationship. Good predictive r(pred)(2) values for CoMFA and CoMSIA models reflected the robustness of the predictive ability. This was validated by designing five new analogues (46-50), which were potently microbicidal (3-10 and 10-20 times against MTZ-susceptible and -resistant TV, respectively) and spermicidal. This in vitro study may have significant clinical relevance, which could become evident in due course.