4,5-Dichloro-1-(naphthalen-2-ylmethyl)-3-(quinolin-2-ylmethyl)imidazolium bromide | 1404549-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4,5-Dichloro-1-(naphthalen-2-ylmethyl)-3-(quinolin-2-ylmethyl)imidazolium bromide
• 英文别名: 2-[[4,5-dichloro-3-(naphthalen-2-ylmethyl)imidazol-3-ium-1-yl]methyl]quinoline;bromide
• CAS: 1404549-70-7
• 化学式: Br*C₂₄H₁₈Cl₂N₃
• 分子量: 499.237
• InChiKey: VIPFEDAEHIDBEG-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氯甲基喹啉盐酸盐 在 potassium hydroxide 作用下， 以 乙腈 为溶剂， 反应 5.75h， 生成 4,5-Dichloro-1-(naphthalen-2-ylmethyl)-3-(quinolin-2-ylmethyl)imidazolium bromide
  参考文献：
  名称：

  Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model

  摘要：

  摘要 我们介绍了一系列新型小分子膀胱脱落剂，它们有望在泌尿系统疾病的临床前研究中发挥重要作用，而且与以前的药物相比具有更好的转化潜力。泌尿科对此类脱落剂的治疗潜力有着广泛的兴趣。临床前模型中使用的主要制剂是阳离子肽硫酸原胺（PS），由于存在全身不良反应和膀胱组织损伤等问题，其转化潜力有限。膀胱内应用一种安全、全身无毒的脱落剂可能有助于根除 大肠杆菌 膀胱炎以及慢性膀胱疼痛和膀胱癌。在这里，我们介绍了一系列对膀胱上皮具有强效和集中脱落活性的咪唑鎓盐。这些化合物的合成和纯化过程简单且可扩展，在冻干状态下具有长期稳定性。该化合物家族的大多数成员对培养的尿路上皮细胞都具有细胞毒性，不同系列化合物的效力相差 10 倍。在对小鼠膀胱局部（膀胱内）施用所选化合物时，只需生理相关的咪唑浓度和短暂的接触时间，就能使上皮细胞完全脱落。通过显微镜、免疫荧光和免疫印迹法检测尿棘蛋白，与 PS 相比，这些化合物的脱落活性明显提高。膀胱尿路上皮可在数天内再生，组织学外观正常，且未观察到毒性。最后，这种化学支架还提供了加入抗菌剂或与化疗药物或其他分子共轭的机会。

  DOI：

  10.1128/aac.00881-15

文献信息

• [EN] AZOLIUM AND PURINIUM SALT ANTICANCER AND ANTIMICROBIAL AGENTS<br/>[FR] ANTIMICROBIENS ET ANTINÉOPLASIQUES DE SELS D'AZOLIUM ET DE PURINIUM
  申请人：UNIV AKRON

  公开号：WO2012149523A1

  公开（公告）日：2012-11-01

  Singly and multiply charged imidazolium cations (ICs) have been identified as a class of chemical compositions that possess potent antineoplastic, antibacterial and antimicrobial properties. The imidazolium cations disclosed demonstrate greater or equivalent potency towards cancerous cells as the current clinical standard, cisplatin. These imidazolium cations, however, achieve this efficacy without any of the known toxic side effects caused by heavy metal-based antineoplastic drugs such as cisplatin.

  单电荷和多电荷咪唑阳离子（ICs）已被确认为一类具有强效抗肿瘤、抗菌和抗微生物特性的化学成分。所披露的咪唑阳离子对癌细胞表现出比当前临床标准顂铂更高或相等的效力。然而，这些咪唑阳离子在不引起类似顂铂等重金属抗肿瘤药物已知的毒副作用的情况下实现了这种功效。
• AZOLIUM AND PURINIUM SALT ANTICANCER AND ANTIMICROBIAL AGENTS
  申请人：Youngs Wiley

  公开号：US20140142307A1

  公开（公告）日：2014-05-22

  Singly and multiply charged imidazolium cations (ICs) have been identified as a class of chemical compositions that possess potent antineoplastic, antibacterial and antimicrobial properties. The imidazolium cations disclosed demonstrate greater or equivalent potency towards cancerous cells as the current clinical standard, cisplatin. These imidazolium cations, however, achieve this efficacy without any of the known toxic side effects caused by heavy metal-based antineoplastic drugs such as cisplati.

  单电荷和多电荷咪唑阳离子（ICs）已被确定为一类具有强效抗肿瘤、抗菌和抗微生物特性的化学成分。所公开的咪唑阳离子在对癌细胞的作用上表现出与当前临床标准药物顺铂相当或更强的效力。然而，这些咪唑阳离子在不像顺铂这样的重金属抗肿瘤药物所知的毒性副作用下，就能实现这种功效。
• Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines
  作者：Brian D. Wright、Michael C. Deblock、Patrick O. Wagers、Ernest Duah、Nikki K. Robishaw、Kerri L. Shelton、Marie R. Southerland、Michael A. DeBord、Kortney M. Kersten、Lucas J. McDonald、Jason A. Stiel、Matthew J. Panzner、Claire A. Tessier、Sailaja Paruchuri、Wiley J. Youngs

  DOI：10.1007/s00044-015-1330-z

  日期：2015.7

  The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-small-cell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.
• US9278951B2
  申请人：——

  公开号：US9278951B2

  公开（公告）日：2016-03-08
• Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model
  作者：Patrick O. Wagers、Kristin M. Tiemann、Kerri L. Shelton、William G. Kofron、Matthew J. Panzner、Karen L. Wooley、Wiley J. Youngs、David A. Hunstad

  DOI：10.1128/aac.00881-15

  日期：2015.9

  We present a novel family of small-molecule urinary bladder exfoliants that are expected to be of great value in preclinical studies of urologic conditions and have improved potential for translation compared with prior agents. There is broad urologic interest in the therapeutic potential of such exfoliating agents. The primary agent used in preclinical models, the cationic peptide protamine sulfate (PS), has limited translational potential due to concerns including systemic adverse reactions and bladder tissue injury. Intravesical application of a safe, systemically nontoxic exfoliant would have potential utility in the eradication of Escherichia coli and other uropathogens that reside in the bladder epithelium following cystitis, as well as in chronic bladder pain and bladder cancer. Here, we introduce a family of imidazolium salts with potent and focused exfoliating activity on the bladder epithelium. Synthesis and purification were straightforward and scalable, and the compounds exhibited prolonged stability in lyophilized form. Most members of the compound family were cytotoxic to cultured uroepithelial cells, with >10-fold differences in potency across the series. Upon topical (intravesical) administration of selected compounds to the murine bladder, complete epithelial exfoliation was achieved with physiologically relevant imidazolium concentrations and brief contact times. The exfoliative activity of these compounds was markedly improved in comparison to PS, as assessed by microscopy, immunofluorescence, and immunoblotting for uroplakins. Bladder uroepithelium regenerated within days to yield a histologically normal appearance, and no toxicity was observed. Finally, the chemical scaffold offers an opportunity for inclusion of antimicrobials or conjugation with chemotherapeutic or other moieties.

  摘要 我们介绍了一系列新型小分子膀胱脱落剂，它们有望在泌尿系统疾病的临床前研究中发挥重要作用，而且与以前的药物相比具有更好的转化潜力。泌尿科对此类脱落剂的治疗潜力有着广泛的兴趣。临床前模型中使用的主要制剂是阳离子肽硫酸原胺（PS），由于存在全身不良反应和膀胱组织损伤等问题，其转化潜力有限。膀胱内应用一种安全、全身无毒的脱落剂可能有助于根除 大肠杆菌 膀胱炎以及慢性膀胱疼痛和膀胱癌。在这里，我们介绍了一系列对膀胱上皮具有强效和集中脱落活性的咪唑鎓盐。这些化合物的合成和纯化过程简单且可扩展，在冻干状态下具有长期稳定性。该化合物家族的大多数成员对培养的尿路上皮细胞都具有细胞毒性，不同系列化合物的效力相差 10 倍。在对小鼠膀胱局部（膀胱内）施用所选化合物时，只需生理相关的咪唑浓度和短暂的接触时间，就能使上皮细胞完全脱落。通过显微镜、免疫荧光和免疫印迹法检测尿棘蛋白，与 PS 相比，这些化合物的脱落活性明显提高。膀胱尿路上皮可在数天内再生，组织学外观正常，且未观察到毒性。最后，这种化学支架还提供了加入抗菌剂或与化疗药物或其他分子共轭的机会。