N-(4-bromobenzyl)-1-isopropyl-1H-benzimidazol-2-amine

• 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: N-(4-bromobenzyl)-1-isopropyl-1H-benzimidazol-2-amine
• 英文别名: N-[(4-bromophenyl)methyl]-1-propan-2-ylbenzimidazol-2-amine
• 化学式: C₁₇H₁₈BrN₃
• mdl: MFCD05625854
• 分子量: 344.254
• InChiKey: AFLSJFCCDCGEOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 N-(4-bromobenzyl)-1-isopropyl-1H-benzimidazol-2-amine
  参考文献：
  名称：

  In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species

  摘要：

  The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L braziliensis 9 and L donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had 1050 values in the micromolar range against the amastigote of L mexicana and L braziliensis. However, both compounds did not show better activity against L donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives. (C) 2017 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.exppara.2017.11.009

文献信息

• In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species
  作者：Rocío Nieto-Meneses、Rafael Castillo、Alicia Hernández-Campos、Armando Maldonado-Rangel、Jeferson B. Matius-Ruiz、Pedro Josué Trejo-Soto、Benjamín Nogueda-Torres、Ma. Auxiliadora Dea-Ayuela、Francisco Bolás-Fernández、Carlos Méndez-Cuesta、Lilián Yépez-Mulia

  DOI：10.1016/j.exppara.2017.11.009

  日期：2018.1

  The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L braziliensis 9 and L donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had 1050 values in the micromolar range against the amastigote of L mexicana and L braziliensis. However, both compounds did not show better activity against L donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives. (C) 2017 Elsevier Inc. All rights reserved.