methyl 1-methyl-2-(trifluoromethyl)-1H-benzimidazole-6-carboxylate | 1375485-65-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: methyl 1-methyl-2-(trifluoromethyl)-1H-benzimidazole-6-carboxylate
• 英文别名: Methyl 3-methyl-2-(trifluoromethyl)benzimidazole-5-carboxylate
• CAS: 1375485-65-6
• 化学式: C₁₁H₉F₃N₂O₂
• 分子量: 258.2
• InChiKey: NDGCUMRRSSZHCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 1-methyl-2-(trifluoromethyl)-1H-benzimidazole-6-carboxylate 在 水 、 N,N'-羰基二咪唑 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 1-methyl-N-(5-nitro-1,3-thiazol-2-yl)-2-(trifluoromethyl)-1H-benzimidazole-6-carboxamide
  参考文献：
  名称：

  Synthesis and antiprotozoal activity of nitazoxanide–N-methylbenzimidazole hybrids

  摘要：

  A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used as drug standards. Experimental evaluations revealed all of the new compounds (1-13) were active and showed strong activity against the three protozoa, particularly with E. histolytica where the IC50 values ranged between 3 and 69 nM.Overall, compounds 2, 5, 7, 8, 9, 11 and 12 stood out with values lower than 87 nM for all three protozoa, comparatively better than the reference drugs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.011
• 作为产物：
  描述：

  3-(甲基氨基)-4-硝基苯羧酸甲酯 在 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 methyl 1-methyl-2-(trifluoromethyl)-1H-benzimidazole-6-carboxylate
  参考文献：
  名称：

  Synthesis and antiprotozoal activity of nitazoxanide–N-methylbenzimidazole hybrids

  摘要：

  A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used as drug standards. Experimental evaluations revealed all of the new compounds (1-13) were active and showed strong activity against the three protozoa, particularly with E. histolytica where the IC50 values ranged between 3 and 69 nM.Overall, compounds 2, 5, 7, 8, 9, 11 and 12 stood out with values lower than 87 nM for all three protozoa, comparatively better than the reference drugs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.011

文献信息

• Exploring the interplay of physicochemical properties, membrane permeability and giardicidal activity of some benzimidazole derivatives
  作者：Carlos Hernández-Covarrubias、Miguel A. Vilchis-Reyes、Lilian Yépez-Mulia、Remedios Sánchez-Díaz、Gabriel Navarrete-Vázquez、Alicia Hernández-Campos、Rafael Castillo、Francisco Hernández-Luis

  DOI：10.1016/j.ejmech.2012.03.014

  日期：2012.6

  This study evaluated the relationship between the physicochemical properties, membrane permeability and in vitro giardicidal activity of twenty nine benzimidazole derivatives (1-7n). The retention time data from reverse phase high performance chromatography (RP-HPLC) were used to estimate aqueous solubility and lipophilicity of these compounds. The apparent permeability was determined using Caco-2 cell monolayer. The calculation of some descriptors, such as Clog P. PSA, was performed using ACD labs software. For benzimidazole derivatives with NHCOOCH3, CH3, NH2, SH and SCH3 groups at the 2-position, a quadratic type of regression model was obtained with giardicidal activity and aqueous solubility or lipophilicity. On the other hand, giardicidal activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives was influenced by lipophilicity, hydrogen bond donors and molecular volume but it was not determined by their apparent permeability in Caco-2 cell line. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M4 positive allosteric modulator (PAM) chemotype
  作者：Kayla J. Temple、Julie L. Engers、Madeline F. Long、Katherine J. Watson、Sichen Chang、Vincent B. Luscombe、Matthew T. Jenkins、Alice L. Rodriguez、Colleen M. Niswender、Thomas M. Bridges、P. Jeffrey Conn、Darren W. Engers、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2019.126812

  日期：2020.2

  This Letter details our efforts to discover structurally unique M-4 PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exercise identified a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide core that provided improved M-4 PAM activity and CNS penetration.
• Synthesis and antiprotozoal activity of nitazoxanide–N-methylbenzimidazole hybrids
  作者：Olivia Soria-Arteche、Alicia Hernández-Campos、Lilián Yépez-Mulia、Pedro Josué Trejo-Soto、Francisco Hernández-Luis、Jorge Gres-Molina、Luis A. Maldonado、Rafael Castillo

  DOI：10.1016/j.bmcl.2013.10.011

  日期：2013.12

  A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used as drug standards. Experimental evaluations revealed all of the new compounds (1-13) were active and showed strong activity against the three protozoa, particularly with E. histolytica where the IC50 values ranged between 3 and 69 nM.Overall, compounds 2, 5, 7, 8, 9, 11 and 12 stood out with values lower than 87 nM for all three protozoa, comparatively better than the reference drugs. (C) 2013 Elsevier Ltd. All rights reserved.