| 747356-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• CAS: 747356-47-4
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: AQRGOXSPTPFZDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  54.98
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  对氨基苯酚 、 在 碳酸氢钠 作用下， 以 乙醚 、 水 为溶剂， 以49%的产率得到N‑(4‑hydroxyphenyl)‑2‑(4‑methoxyphenyl)‑1H‑benzimidazole‑5‑carboxamide
  参考文献：
  名称：

  作为选择性丁酰胆碱酯酶抑制剂的新型甲酰胺和甲酰肼苯并咪唑的合成

  摘要：

  假设选择性抑制丁酰胆碱酯酶 (BChE) 有助于治疗阿尔茨海默病 (AD)。几项研究确定了 BChE 活性增加与 AD 发病之间的相关性。BChE 优于乙酰胆碱酯酶抑制的一个优势是 BChE 活性的缺失不会导致明显的生理障碍。然而，目前没有 BChE 抑制剂可作为 AD 的潜在治疗剂在商业上获得。在我们不断努力寻找有效的阿尔茨海默病 BChE 抑制剂的过程中，本研究共合成了 22 种具有多种取代的新型苯并咪唑，并评估了它们的抗胆碱酯酶活性。在合成的化合物中，2j和3f被发现表现出有效和选择性的 BChE 抑制作用，IC 50值分别为 1.13 和 1.46 μM。进行分子对接研究以合理化观察到的抑制活性。预计这些化合物具有高穿透血脑屏障的能力。此外，还进行了细胞增殖研究以评估感兴趣化合物的毒性特征。 图形概要 发现化合物3f是一种有效的选择性丁酰胆碱酯酶抑制剂，IC 50值为 1.46 µM。

  DOI：

  10.1007/s11030-022-10476-8
• 作为产物：
  描述：

  sodium hydroxy(4-methoxyphenyl)methanesulfonate 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  作为选择性丁酰胆碱酯酶抑制剂的新型甲酰胺和甲酰肼苯并咪唑的合成

  摘要：

  假设选择性抑制丁酰胆碱酯酶 (BChE) 有助于治疗阿尔茨海默病 (AD)。几项研究确定了 BChE 活性增加与 AD 发病之间的相关性。BChE 优于乙酰胆碱酯酶抑制的一个优势是 BChE 活性的缺失不会导致明显的生理障碍。然而，目前没有 BChE 抑制剂可作为 AD 的潜在治疗剂在商业上获得。在我们不断努力寻找有效的阿尔茨海默病 BChE 抑制剂的过程中，本研究共合成了 22 种具有多种取代的新型苯并咪唑，并评估了它们的抗胆碱酯酶活性。在合成的化合物中，2j和3f被发现表现出有效和选择性的 BChE 抑制作用，IC 50值分别为 1.13 和 1.46 μM。进行分子对接研究以合理化观察到的抑制活性。预计这些化合物具有高穿透血脑屏障的能力。此外，还进行了细胞增殖研究以评估感兴趣化合物的毒性特征。 图形概要 发现化合物3f是一种有效的选择性丁酰胆碱酯酶抑制剂，IC 50值为 1.46 µM。

  DOI：

  10.1007/s11030-022-10476-8

文献信息

• Novel Clarithromycin Analogs with C-4” 2-arylbenzimidazolyl Bishydrazide Side Chain: Synthesis and Antibacterial Evaluation
  作者：Yunkun Qi、Ruixin Ma、Xin Li、Yue Hu、Siti Ma、Chao Cong、Xiaodong Ma、Wenping Cui、Shutao Ma

  DOI：10.2174/157018011797655269

  日期：2011.12.1

  A series of novel 4” -O-2-arylbenzimidazolyl derivatives of clarithromycin were synthesized and evaluated. These 4” -O-2-arylbenzimidazolyl derivatives demonstrated excellent activity against erythromycin-susceptible strains and showed remarkably improved activity against erythromycin-resistant strains compared with the references. In particular, compound 7c, which possesses the terminal 2-(2-methoxyphenyl)benzimidazolyl group on the C-4” bishydrazide side chain, not only presented the most potent activity against erythromycin-susceptible Streptococcus pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923, exhibiting 4-fold and 4-fold higher efficacy than the parent clarithromycin, but also displayed the highest activity against erythromycin-resistant Streptococcus pneumoniae expressing the mef gene and the erm gene, which was 133-fold and 32-fold better than clarithromycin or azithromycin, respectively.

  一系列新型的克拉霉素4”-O-2-芳基苯并咪唑衍生物被合成并评估。这些4”-O-2-芳基苯并咪唑衍生物对红霉素敏感菌株显示出优异的活性，并且相较于参考药物，对红霉素耐药菌株的活性显著提高。特别是化合物7c，其在C-4”双酰肼侧链上带有末端的2-（2-甲氧基苯基）苯并咪唑基团，不仅对红霉素敏感的肺炎链球菌ATCC49619和金黄色葡萄球菌ATCC25923表现出最强的活性，效能分别是母体克拉霉素的4倍和4倍，而且对表达mef基因和erm基因的红霉素耐药肺炎链球菌的活性也是最高的，分别是克拉霉素或阿奇霉素的133倍和32倍。
• Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives
  作者：Chao Cong、Haiyang Wang、Yue Hu、Chen Liu、Siti Ma、Xin Li、Jichao Cao、Shutao Ma

  DOI：10.1016/j.ejmech.2011.04.004

  日期：2011.7

  Novel 4 ''-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These benzimidazolyl derivatives exhibited excellent activity against erythromycin-susceptible strains better than the references, and some of them showed greatly improved activity against erythromycin-resistant strains. Compounds 16 and 17, which have the terminal 2-(4-methylphenyl)benzimidazolyl and 2-(2-methoxyphenyl)benzimidazolyl groups on the C-4 '' bishydrazide side chains, were the most active against erythromycin-resistant Staphylococcus pneumoniae expressing the erm gene and the me! gene. In addition, compound 17 exhibited the highest activity against erythromycin-susceptible S. pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923 as well. It is worth noting that the 4 ''-O-(2-aryl)benzimidazolyl derivatives show higher activity against erythromycin-susceptible and erythromycin-resistant strains than the 4 ''-O-(2-alkyl) benzimidazolyl derivatives. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis of some new benzimidazolecarboxamides and evaluation of their antimicrobial activity
  作者：Hakan Göker、Meral Tunçbilek、Gülgün Ayhan、Nurten Altanlar

  DOI：10.1016/s0014-827x(98)00045-7

  日期：1998.6

  A series of 1,2-disubstituted benzimidazole-5(6)-carboxamides was prepared and evaluated in vitro for antimicrobial activity against Staphyloccus aureus, Escherichia coli and Candida albicans. The precursor benzimidazolecarboxylic acids 4a-c and 9a-c were prepared via oxidative condensation of diaminobenzoic acids with aldehydes and via several steps over the 2(1H)-benzimidazolones, respectively. All acids were converted to their acyl chlorides with SOCI2, then amidified with several N,N'-dialkylaminoethyl derivatives. Compounds 8a-c, 20 and 22 exhibited the best activity. (C) 1998 Elsevier Science S.A. All rights reserved.
• Goeker, Hakan; Tebrizli, Emin; Abbasoglu, Ufuk, Il Farmaco, 1996, vol. 51, # 1, p. 53 - 58
  作者：Goeker, Hakan、Tebrizli, Emin、Abbasoglu, Ufuk

  DOI：——

  日期：——
• Hx, a Novel Fluorescent, Minor Groove and Sequence Specific Recognition Element: Design, Synthesis, and DNA Binding Properties of <i>p</i>-Anisylbenzimidazole-imidazole/pyrrole-Containing Polyamides
  作者：Sameer Chavda、Yang Liu、Balaji Babu、Ryan Davis、Alan Sielaff、Jennifer Ruprich、Laura Westrate、Christopher Tronrud、Amanda Ferguson、Andrew Franks、Samuel Tzou、Chandler Adkins、Toni Rice、Hilary Mackay、Jerome Kluza、Sharjeel A Tahir、Shicai Lin、Konstantinos Kiakos、Chrystal D. Bruce、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1021/bi102028a

  日期：2011.4.19

  With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Fix-containing polyamides gave binding constants in the 10(6) M-1 range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formainido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Fix moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (Delta T-M), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells.