1-decyl-4-(hydroxymethyl)-3-methyl-1H-1,2,3-triazol-3-ium iodide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-decyl-4-(hydroxymethyl)-3-methyl-1H-1,2,3-triazol-3-ium iodide
• 英文别名: (1-Decyl-3-methyltriazol-1-ium-4-yl)methanol;iodide；(1-decyl-3-methyltriazol-1-ium-4-yl)methanol;iodide
• 化学式: C₁₄H₂₈N₃O*I
• 分子量: 381.3
• InChiKey: BWCAWWYZLSQINT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.66
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-decyl-4-(hydroxymethyl)-3-methyl-1H-1,2,3-triazol-3-ium iodide 在 sodium bromide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以90%的产率得到1-decyl-4-(hydroxymethyl)-3-methyl-1H-1,2,3-triazol-3-ium bromide
  参考文献：
  名称：

  用于高效 CO2 转化的单组分、无金属、无溶剂 H2O 官能化 1,2,3-三唑基离子液体催化剂

  摘要：

  一系列带有不同烷基链和反阴离子的 H2O 功能化 1,2,3-三唑离子液体 ( 1-9b ) 被评估为绿色、单组分、双功能催化剂，用于涉及 CO 2和环氧化物的环加成反应。它们是使用廉价、无毒和广泛可用的起始材料通过清洁、简便和高产率的三步程序制备的。化合物1-9b通过光谱技术进行了表征， 3b的分子结构也通过单晶X射线衍射。催化结果证明羟基和抗衡阴离子之间的协同作用对于实现出色的周转频率 (TOF) 至关重要。平行地，中性三唑在相同反应条件下表现出非常低的活性。使用最佳反应条件（25 mmol 环氧化物、140 °C、30 bar CO 2和 1 小时），实现了所有末端环氧化物的高转化率，包括在产生 667 小时出色 TOF 值的放大实验中-1。此外，使用氧化环己烯的反应仅在 6 小时内就实现了 85% 的转化率。总之，我们的结果显示了 H2O 功能化 1,2,3-三唑基离子液体催化剂对高效

  DOI：

  10.1039/d2nj02052a
• 作为产物：
  描述：

  1-叠氮癸烷 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 72.0h， 生成 1-decyl-4-(hydroxymethyl)-3-methyl-1H-1,2,3-triazol-3-ium iodide
  参考文献：
  名称：

  1,2,3-三唑衍生物：合成、对接、细胞毒性分析和体内抗疟活性

  摘要：

  疟疾仍然是世界上最重要的寄生虫病之一。多重耐药疟原虫菌株使目前可用于疟疾的治疗效果较差。因此，必须开发新药来克服治疗耐药性。三唑衍生物表现出多种生物活性，并提供了一个从生物学角度看有前途的部分。由于与 NADH 的结构相似，人们认为三唑类化合物可以与乳酸疟原虫脱氢酶 (pLDH)的活性位点结合。目前的工作通过计算机、体外和体内研究评估了 1,2,3-三唑衍生物的抗疟活性。初步的对化合物的计算机模拟 ADMET 研究显示出良好的药代动力学特性。对伯氏疟原虫（Pb LDH）LDH的电子对接分析表明，所有化合物都与活性位点的催化残基相互作用，亲和力与氯喹相似；最常见的抗疟药。体外评估了这些衍生物的细胞毒性和溶血作用。化合物1，2，5，8，和9被证明是在执行的测试的非细胞毒性的。体内抗疟活性使用感染了伯氏疟原虫NK65。测试的五种化合物在感染后 9 天都表现出抗疟活性。化合物5显示出有希望的活性，抑制了约

  DOI：

  10.1016/j.cbi.2021.109688

文献信息

• Effect of 1,2,3-triazole salts, non-classical bioisosteres of miltefosine, on Leishmania amazonensis
  作者：Pedro H.F. Stroppa、Luciana M.R. Antinarelli、Arturene M.L. Carmo、Jacy Gameiro、Elaine S. Coimbra、Adilson D. da Silva

  DOI：10.1016/j.bmc.2017.03.051

  日期：2017.6

  Here, we report the effect of new non-classical bioisosteres of miltefosine on Leishmania amazonensis. Fifteen compounds were synthesized and the compound dhmtAc, containing an acetate anion, a side chain of 10 carbon atoms linked to N-1 and a methyl group linked to N-3, showed high and selective biological activity against L. amazonensis. On the intracellular amastigotes, stages of the parasite related to human disease, the IC50 values were near or similar to the 1.0 mu M (0.9, 0.8 and 1.0 mu M on L. amazonensis-WT, and two transgenic L. amazonensis expressing GFP and RFP, respectively), being more active than miltefosine. Furthermore, dhmtAc did not show toxic effects on human erythrocytes and macrophages (CC50 = 115.91 mu M) being more destructive to the intracellular parasites (selectivity index > 115). Promastigotes and intramacrophage amastigotes treated with dhmtAc showed low capacity for reversion of the effect of the compound. A study of the mechanism of action of this compound showed some features of metazoan apoptosis, including cell volume decreases, loss of mitochondrial membrane potential, ROS production, an increase in the intracellular lipid bodies, in situ labeling of DNA fragments by TUNEL labeling and phosphatidylserine exposure to the outerleaflet of the plasma membrane. In addition, the plasma membrane disruption, revealed by PI labeling, suggests cell death by necrosis. No increase in autophagic vacuoles formation in treated promastigotes was observed. Taken together, the data indicate that the bioisostere of miltefosine, dhmtAc, has promising antileishmanial activity that is mediated via apoptosis and necrosis. (C) 2017 Elsevier Ltd. All rights reserved.
• Novel functionalized 1,2,3-triazole derivatives exhibit antileishmanial activity, increase in total and mitochondrial-ROS and depolarization of mitochondrial membrane potential of Leishmania amazonensis
  作者：Raíssa Soares Meinel、Ayla das Chagas Almeida、Pedro Henrique Fazza Stroppa、Nícolas Glanzmann、Elaine Soares Coimbra、Adilson David da Silva

  DOI：10.1016/j.cbi.2019.108850

  日期：2020.1

  1,2,3-triazolium salts are poorly understood regarding their antileishmanial activity. Hence, as an effort to identify novel chemical scaffolds as antileishmanial agents, a series of 1,2,3-triazolium salts (TS) and corresponding 1,2,3-triazole (T) precursors including new epoxide derivatives were synthesized and assayed against Leishmania amazonensis promastigote and intracellular amastigote forms. Among them, the compound TS-6 exhibited promising activity on promastigotes (IC50 = 3.61 mu M) and intracellular amastigotes (IC50 = 7.61 mu M) of L. amazonensis, superior to miltefosine (IC50 > 10.0 mu M), used as reference drug. In addition, TS-6 showed negligible cytotoxicity on murine peritoneal macrophages with a SI of about 10. Studies on the mode of action of TS-6 indicate mitochondrial dysfunction through an increase in 'total' and mitochondrial-ROS as well as depolarization of mitochondrial membrane potential of L. amazonensis promastigotes. In silico physicochemical studies indicate that the TS-6 could potentially be used as an oral drug.
• Correlation of structural features of novel 1,2,3-triazoles with their neurotoxic and tumoricidal properties
  作者：Elaine Maria de Souza-Fagundes、Johannes Delp、PedroH.D.M. Prazeres、Lucas Bonfim Marques、Arturene Maria Lino Carmo、Pedro Henrique Fazza Stroppa、Nicolas Glanzmann、Jaffar Kisitu、Dàvid Szamosvàri、Thomas Böttcher、Marcel Leist、Adilson David da Silva

  DOI：10.1016/j.cbi.2018.06.029

  日期：2018.8

  Triazoles are interesting templates for novel chemotherapeutic drugs. We synthesized here 17 1,3,4-substituted-1,2,3-triazoles that differed in their l'-substituent (variable alkyl chain lengths C3-C12), the 3'-substituent (no substituent, -methyl or -propyl) or the salt form obtained. Several of the compounds were cytotoxic (mu M range) for tumor cells (HL-60, Jurkat, MCF-7, HCT-116), and when the effect was compared to non-transformed cells (Vero), selectivity ratios of up to 23-fold were obtained. To estimate the liability of these potential drug candidates for triggering neurotoxicity, we used the LUHMES cell-based NeuriTox assay. This test quantifies damage to the neurites of human neurons. The four most potent tumoricidal compounds were found to be neurotoxic in a concentration range similar to the one showing tumor cell toxicity. As the neurites of the LUHMES neurons were affected at > 4-fold lower concentrations than the overall cell viability, the novel triazoles were classified as specific neurotoxicants. The structure-activity relationship (SAR) for neurotoxicity was sharply defined and correlated with the one for anti-neoplastic activity. Based on this SAR, two non-neurotoxic compounds were predicted, and testing in the NeuriTox assay confirmed this prediction. In summary, the panel of novel triazoles generated and characterized here, allowed to define structural features associated with cytotoxicity and neurotoxicity. Moreover, the study shows that potential neurotoxic side effects may be predicted early in drug development if highly sensitive test methods for neurite integrity are applied.