1-(4-fluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-triazole | 1315307-41-5

• 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-(4-fluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-triazole
• 英文别名: Methyl 5-cyclohexyl-1-(4-fluorophenyl)-1,2,4-triazole-3-carboxylate
• CAS: 1315307-41-5
• 化学式: C₁₆H₁₈FN₃O₂
• 分子量: 303.336
• InChiKey: DLTDRPYRVHVJLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-triazole 在 sodium tetrahydroborate 、 戴斯-马丁氧化剂 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  1,2,4-三唑衍生物作为有效抗结核药物的设计、合成和生物学评价

  摘要：

  抑制分枝杆菌膜蛋白大3（MmpL3）从而影响分枝菌酸生物合成途径已被证明是开发抗结核药物的有效策略。基于MmpL3抑制剂复合物的X射线晶体结构，设计、合成了一系列新型1,2,4-三唑衍生物，并评估了其对Mtb菌株H37Rv的抗结核活性。全面的构效关系探索鉴定出化合物21和28，它们对Mtb菌株 H37Rv [最低抑菌浓度 (MIC) = 0.03–0.13 μg/mL] 和多重耐药 (MDR) 临床分离株具有有效的抗结核活性和广泛耐药 (XDR) 结核病 (MIC = 0.06–1.0 μg/mL)。此外，根据计算机吸收、分布、代谢和排泄 (ADME) 预测，化合物21和28对哺乳动物 Vero 细胞显示出可忽略的细胞毒性 (IC 50 ≥ 32 μg/mL) 和良好的理化和药代动力学特性。最后，使用微量热泳 (MST) 测定将代表性 1,2,4-三唑28的潜在靶标确定为 MmpL3。

  DOI：

  10.1016/j.cclet.2023.108464
• 作为产物：
  描述：

  环己烷基甲醛 在 盐酸羟胺 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 1-(4-fluorophenyl)-3-methoxycarbonyl-5-cyclohexyl-1,2,4-triazole
  参考文献：
  名称：

  1,2,4-三唑衍生物作为有效抗结核药物的设计、合成和生物学评价

  摘要：

  抑制分枝杆菌膜蛋白大3（MmpL3）从而影响分枝菌酸生物合成途径已被证明是开发抗结核药物的有效策略。基于MmpL3抑制剂复合物的X射线晶体结构，设计、合成了一系列新型1,2,4-三唑衍生物，并评估了其对Mtb菌株H37Rv的抗结核活性。全面的构效关系探索鉴定出化合物21和28，它们对Mtb菌株 H37Rv [最低抑菌浓度 (MIC) = 0.03–0.13 μg/mL] 和多重耐药 (MDR) 临床分离株具有有效的抗结核活性和广泛耐药 (XDR) 结核病 (MIC = 0.06–1.0 μg/mL)。此外，根据计算机吸收、分布、代谢和排泄 (ADME) 预测，化合物21和28对哺乳动物 Vero 细胞显示出可忽略的细胞毒性 (IC 50 ≥ 32 μg/mL) 和良好的理化和药代动力学特性。最后，使用微量热泳 (MST) 测定将代表性 1,2,4-三唑28的潜在靶标确定为 MmpL3。

  DOI：

  10.1016/j.cclet.2023.108464

文献信息

• Synthesis and antiproliferative evaluation of 3,5-disubstituted 1,2,4-triazoles containing flurophenyl and trifluoromethanephenyl moieties
  作者：Li-Ya Wang、Wen-Che Tseng、Tian-Shung Wu、Kimiyoshi Kaneko、Hiroyuki Takayama、Masayuki Kimura、Wen-Chin Yang、Jin Bin Wu、Shin-Hun Juang、Fung Fuh Wong

  DOI：10.1016/j.bmcl.2011.07.009

  日期：2011.9

  An efficient 1,3-dipolar cycloaddition method was performed for the synthesis of a series of monofluoroand trifluoromethane-3,5-disubstituted 1,2,4-triazoles. This efficient cycloaddition method was to react hydrazonoyl hydrochlorides with a series of aldehydes in the presence of NEt(3) as catalytic basic agent to provide the corresponding product in 28-94%. Their growth inhibitory results against cancer cells indicated that some of the fluorine-and trifluoromethane-containing compounds could effectively inhibit the growth of NCI-H226 and T-cell leukemia (Jurkat) cells. Among the compounds, trifluoromethane-containing 1,2, 4-triazoles possessed the five-membered ring groups on the C-5 position of the triazolic ring, including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl, possessed the significant inhibitory activity for NCI-H226 cancer cells. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
• ‘One-flask’ synthesis to 3,5-disubstituted 1,2,4-triazoles from aldehydes with hydrazonoyl hydrochlorides via 1,3-dipolar cycloaddition
  作者：Wen-Che Tseng、Li-Ya Wang、Tian-Shung Wu、Fung Fuh Wong

  DOI：10.1016/j.tet.2011.05.003

  日期：2011.7

  A new 'one-flask' synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to synthesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cycloaddition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this 'one-flask' 1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine under basic condition. Furthermore, this newly developed methodology can be applied to various aldehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
• An Effective Nitrilimine Cycloaddition for the Synthesis of 1,3,5-Trisubstituted 1,2,4-Triazoles from Oximes with Hydrazonoyl Hydrochlorides
  作者：Fung Wong、Li-Ya Wang、Wen-Che Tseng、Hui-Yi Lin

  DOI：10.1055/s-0030-1260759

  日期：2011.6

  An effective 1,3-dipolar cycloaddition for the synthesis of 1,3,5-trisubstituted 1,2,4-triazole derivatives was developed by reacting oximes with hydrazonoyl hydrochlorides using triethylamine as a base. The desired 1,3,5-trisubstituted 1,2,4-triazoles were obtained in good yields and the reaction was applicable to aliphatic, cyclic aliphatic, aromatic and heterocyclic oxime substrates.
• Design, synthesis, and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents
  作者：Yu Wen、Shichun Lun、Yuxue Jiao、Wei Zhang、Tianyu Hu、Ting Liu、Fan Yang、Jie Tang、Bing Zhang、William R. Bishai、Li-Fang Yu

  DOI：10.1016/j.cclet.2023.108464

  日期：2024.3

  for developing antitubercular drugs. Based on the X-ray crystal structure of MmpL3 inhibitor complexes, a series of novel 1,2,4-triazole derivatives were designed, synthesized and evaluated antitubercular activity against Mtb strain H37Rv. Comprehensive structure–activity relationship exploration resulted in the identification of compounds 21 and 28, which possess potent antitubercular activity against

  抑制分枝杆菌膜蛋白大3（MmpL3）从而影响分枝菌酸生物合成途径已被证明是开发抗结核药物的有效策略。基于MmpL3抑制剂复合物的X射线晶体结构，设计、合成了一系列新型1,2,4-三唑衍生物，并评估了其对Mtb菌株H37Rv的抗结核活性。全面的构效关系探索鉴定出化合物21和28，它们对Mtb菌株 H37Rv [最低抑菌浓度 (MIC) = 0.03–0.13 μg/mL] 和多重耐药 (MDR) 临床分离株具有有效的抗结核活性和广泛耐药 (XDR) 结核病 (MIC = 0.06–1.0 μg/mL)。此外，根据计算机吸收、分布、代谢和排泄 (ADME) 预测，化合物21和28对哺乳动物 Vero 细胞显示出可忽略的细胞毒性 (IC 50 ≥ 32 μg/mL) 和良好的理化和药代动力学特性。最后，使用微量热泳 (MST) 测定将代表性 1,2,4-三唑28的潜在靶标确定为 MmpL3。