E-N'-isopropyl-2-(2-furan-2-ylvinyl)-3H-benzimidazole-5-carboxamidine hydrochloride | 1044509-69-4

• 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: E-N'-isopropyl-2-(2-furan-2-ylvinyl)-3H-benzimidazole-5-carboxamidine hydrochloride
• 英文别名: E-2-(2-furan-2-ylvinyl)-N-isopropyl-3H-benzimidazole-6-carboxamidine hydrochloride；2-[(E)-2-(furan-2-yl)ethenyl]-N'-propan-2-yl-3H-benzimidazole-5-carboximidamide;hydrochloride
• CAS: 1044509-69-4
• 化学式: C₁₇H₁₈N₄O*ClH
• 分子量: 330.817
• InChiKey: UBUFDLRGMSEBOL-WVLIHFOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  E-N'-isopropyl-2-(2-furan-2-ylvinyl)-3H-benzimidazole-5-carboxamidine hydrochloride 以 水 为溶剂， 反应 2.0h， 以90%的产率得到1,3-di[5(6)-N-isopropylamidino-2-benzoimidazolyl]-2,4-di(2-furyl)cyclobutane dihydrochloride
  参考文献：
  名称：

  Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors

  摘要：

  A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.

  DOI：

  10.17344/acsi.2015.1605
• 作为产物：
  描述：

  2-呋喃丙烯醛 、 3,4-diamino-N-isopropylbenzamidine hydrochloride 在 对苯醌 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以50%的产率得到E-N'-isopropyl-2-(2-furan-2-ylvinyl)-3H-benzimidazole-5-carboxamidine hydrochloride
  参考文献：
  名称：

  Novel Amidino-Substituted Thienyl- and Furylvinylbenzimidazole: Derivatives and Their Photochemical Conversion into Corresponding Diazacyclopenta[c]fluorenes. Synthesis, Interactions with DNA and RNA, and Antitumor Evaluation. 4

  摘要：

  Synthesis of novel nonfused amidino-substituted thienyl- and furyl vinylbenzimidazole: derivatives and their photochemical cyclization into corresponding diazacyclopenta[c]fluorenes is described. All studied compounds showed prominent growth inhibitor effect. The fused compounds showed stronger activity than nonfused ones, whereby imidazolyl-substituted compound 11 proved to be the most active one. Besides, it induced strong G2/M arrest of the cell cycle followed by drastic apoptosis, which is in accordance with the DNA intercalative binding mode determined by the spectroscopic studies. Nonfused derivatives induced strong S phase arrest of the cell cycle followed by apoptosis that together with DNA minor groove binding mode pointed to topoisomerase I inhibition. In addition, all nonfused compounds revealed pronounced selectivity toward tumor cells in comparison with nontumor cells. Oil the basis of the presented results, both nonfused and fused thiophene-containing, imidazolyl derivatives Should be considered as promising lead compounds for further investigation.

  DOI：

  10.1021/jm8000423

文献信息

• Novel Amidino-Substituted Thienyl- and Furylvinylbenzimidazole: Derivatives and Their Photochemical Conversion into Corresponding Diazacyclopenta[<i>c</i>]fluorenes. Synthesis, Interactions with DNA and RNA, and Antitumor Evaluation. 4
  作者：Marijana Hranjec、Ivo Piantanida、Marijeta Kralj、Lidija Šuman、Krešimir Pavelić、Grace Karminski-Zamola

  DOI：10.1021/jm8000423

  日期：2008.8.1

  Synthesis of novel nonfused amidino-substituted thienyl- and furyl vinylbenzimidazole: derivatives and their photochemical cyclization into corresponding diazacyclopenta[c]fluorenes is described. All studied compounds showed prominent growth inhibitor effect. The fused compounds showed stronger activity than nonfused ones, whereby imidazolyl-substituted compound 11 proved to be the most active one. Besides, it induced strong G2/M arrest of the cell cycle followed by drastic apoptosis, which is in accordance with the DNA intercalative binding mode determined by the spectroscopic studies. Nonfused derivatives induced strong S phase arrest of the cell cycle followed by apoptosis that together with DNA minor groove binding mode pointed to topoisomerase I inhibition. In addition, all nonfused compounds revealed pronounced selectivity toward tumor cells in comparison with nontumor cells. Oil the basis of the presented results, both nonfused and fused thiophene-containing, imidazolyl derivatives Should be considered as promising lead compounds for further investigation.
• Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors
  作者：Vesna Rastija、Dejan Agić、Sanja Tomiš、Sonja Nikolič、Marijana Hranjec、Grace Karminski-Zamola、Marija Abramić

  DOI：10.17344/acsi.2015.1605

  日期：2015.12.15

  A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.