3-(phenylthio)-1-(5-cyclohexylpentyl)quinolinium iodide | 1265087-27-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-(phenylthio)-1-(5-cyclohexylpentyl)quinolinium iodide
• 英文别名: 1-(cyclohexylpentyl)-3-(phenylthio)quinolinium iodide；3-(phenylsulfanyl)-1-(5-cyclohexylpentyl)quinolin-1-ium iodide；1-(5-Cyclohexylpentyl)-3-phenylsulfanylquinolin-1-ium;iodide
• CAS: 1265087-27-1
• 化学式: C₂₆H₃₂NS*I
• 分子量: 517.517
• InChiKey: VKHQXINRQYJHAG-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.42
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-碘喹啉 在 copper(l) iodide 、 potassium carbonate 、 乙二醇 作用下， 以 环丁砜 、 异丙醇 为溶剂， 反应 30.0h， 生成 3-(phenylthio)-1-(5-cyclohexylpentyl)quinolinium iodide
  参考文献：
  名称：

  Optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens

  摘要：

  Ring-opened benzothieno[3,2-b]quinolinium salts (3) were designed and synthesized with substitution on the thiophene moiety. In vitro screenings were carried out against fungal pathogens including Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida krusei and Aspergillus fumigatus. In all, by replacing the N-methyl group (2) with N-omega-phenylpentyl or omega-cyclohexylpentyl group to form substituted 3-(phenylthio)quinolinium compounds produced remarkable potencies, as high as 300-fold (cf. cryptolepine (1) = 250 mu g/mL vs lip = 0.8 mu g/mL for C. albicans) over the starting tetracyclic parent. In addition, all the N-omega-cyclohexylpentyl analogs produced superior activity against all the microorganisms tested than the N-omega-phenylpentyl substituted compounds. The potential of these compounds to induce toxicity in Vero cells was also investigated and the majority of them showed lower or no cytotoxicity at 10 mu g/mL than amphotericin B. the gold standard in antifungal drug development. For instance, the trifluoromethyl substituted analogs (11n-p) have selectivity indices over 2-fold better than those of amphotericin B in C. neoformans. Overall, this ring-opened scafford of benzothienoquinolines, with substitution on the thiophenyl moiety, serves as a new lead for further development. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2011.02.034

文献信息

• Benzothieno[3,2-b]quinolinium and 3-(phenylthio)quinolinium compounds: Synthesis and evaluation against opportunistic fungal pathogens
  作者：Comfort A. Boateng、Suresh V.K. Eyunni、Xue Y. Zhu、Jagan R. Etukala、Barbara A. Bricker、M.K. Ashfaq、Melissa R. Jacob、Shabana I. Khan、Larry A. Walker、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2010.11.008

  日期：2011.1

  Substitution around 5-methyl benzothieno[3,2-b] quinolinium (2) ring system was explored in order to identify positions of substitution that could improve its antifungal profile. The 3-methoxy (10b) was active against C. albicans, C. neoformans, and A. fumigatus and the 4-chloro (10f) analog showed moderate increases in anti-cryptococcal and anti-aspergillus activities. The effectiveness of 10b and 10f were validated in murine models of candidiasis and cryptococcosis, respectively. The efficacy of 10f in reducing brain cryptococcal infection and its observation in the brain of mice injected with this quaternary compound confirm the capacity of these compounds to cross the blood-brain barrier of mice. Overall, several of the chloro and methoxy substituted compounds showed significant improvements in activity against A. fumigatus, the fungal pathogen prevalent in patients receiving organ transplant. Opening the benzothiophene ring of 2 to form 1-(5-cyclohexylpentyl)-3-(phenylthio) quinolinium compound (3) resulted in the identification of several novel compounds with over 50-fold increases in potency (cf. 2) while retaining low cytotoxicities. Thus, compound 3 constitutes a new scaffold for development of drugs against opportunistic infections. Published by Elsevier Ltd.
• Optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens
  作者：Comfort A. Boateng、Xue Y. Zhu、Melissa R. Jacob、Shabana I. Khan、Larry A. Walker、Seth Y. Ablordeppey

  DOI：10.1016/j.ejmech.2011.02.034

  日期：2011.5

  Ring-opened benzothieno[3,2-b]quinolinium salts (3) were designed and synthesized with substitution on the thiophene moiety. In vitro screenings were carried out against fungal pathogens including Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida krusei and Aspergillus fumigatus. In all, by replacing the N-methyl group (2) with N-omega-phenylpentyl or omega-cyclohexylpentyl group to form substituted 3-(phenylthio)quinolinium compounds produced remarkable potencies, as high as 300-fold (cf. cryptolepine (1) = 250 mu g/mL vs lip = 0.8 mu g/mL for C. albicans) over the starting tetracyclic parent. In addition, all the N-omega-cyclohexylpentyl analogs produced superior activity against all the microorganisms tested than the N-omega-phenylpentyl substituted compounds. The potential of these compounds to induce toxicity in Vero cells was also investigated and the majority of them showed lower or no cytotoxicity at 10 mu g/mL than amphotericin B. the gold standard in antifungal drug development. For instance, the trifluoromethyl substituted analogs (11n-p) have selectivity indices over 2-fold better than those of amphotericin B in C. neoformans. Overall, this ring-opened scafford of benzothienoquinolines, with substitution on the thiophenyl moiety, serves as a new lead for further development. Published by Elsevier Masson SAS.