MMV665850

• 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: MMV665850
• 英文别名: 4-Chloro-2-[(1,3-dihydrobenzimidazol-1-ium-2-ylideneamino)methyl]phenolate；4-chloro-2-[(1,3-dihydrobenzimidazol-1-ium-2-ylideneamino)methyl]phenolate
• 化学式: C₁₄H₁₂ClN₃O
• 分子量: 273.722
• InChiKey: CICSCGMRUIMBNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  60.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 MMV665850 以 二甲基亚砜 为溶剂， 以74%的产率得到3‑(1H‑benzo[d]imidazol‑2‑yl)‑6‑chloro‑3,4‑dihydro‑2H‑benzo[e][1,3]oxazine
  参考文献：
  名称：

  苯并咪唑系链 3,4-二氢-2H-苯并[e] [1, 3]恶嗪类抗癌药物的设计、合成

  摘要：

  通过两步合成方案合成了一系列新型 3-(1H-苯并[d]咪唑-2-基)-3,4-二氢-2H-苯并[e][1,3]恶嗪类似物。通过解释1 H NMR、 13 C NMR 和纯化后记录的质谱数据确定了化合物的结构。使用阿霉素作为标准参考，筛选所有标题化合物4a-k对两种乳腺癌细胞系 MCF 7 和 MDA-MB-231 的体外抗癌活性。化合物4e对细胞系 MCF-7 和 MDA-MB-231 均表现出优异的活性，IC 50值分别为8.60 ± 0.75和6.30 ± 0.54 µM ，而多柔比星IC 50值为9.11 ± 0.54和8.47 ± 0.47 µM 。化合物4i还表现出良好的活性，针对 MCF-7 细胞的 IC 50值为9.85 ± 0.69 μM ，与多柔比星相当。化合物4g表现出与标准参考相当的最佳活性，针对 MDA-MB-231 细胞系的 IC 50值为8.52 ± 0.62

  DOI：

  10.1007/s11030-023-10661-3
• 作为产物：
  描述：

  2-(1H-benzimidazol-2-yliminomethyl)-4-chlorophenol 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 MMV665850
  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