3,3,9,9-tetramethyl-7,11-dihydro-1H-[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]pyridin-5-ylmethanol | 1289167-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: 3,3,9,9-tetramethyl-7,11-dihydro-1H-[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]pyridin-5-ylmethanol
• 英文别名: 3,3,9,9-Tetramethyl-7,11-dihydro-1h-[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]-pyridin-5-ylmethanol；(5,5,13,13-tetramethyl-4,6,12,14-tetraoxa-9-azatricyclo[8.5.0.02,7]pentadeca-1,7,9-trien-8-yl)methanol
• CAS: 1289167-06-1
• 化学式: C₁₅H₂₁NO₅
• 分子量: 295.335
• InChiKey: BBRKEBFFTFHUPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,3,9,9-tetramethyl-7,11-dihydro-1H-[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]pyridin-5-ylmethanol 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 20.0h， 以64%的产率得到(2,2-dimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5,6,8-triyl)trimethanol
  参考文献：
  名称：

  Experimental and theoretical study on 6-substituted pyridoxine derivatives. Synthesis of cyclic 2,4,5,6-tetrakis-(hydroxymethyl)pyridin-3-ol acetonides

  摘要：

  Synthetic approaches to three cyclic 2,4,5,6-tetrakis(hydroxymethyl) pyridin-3-ol acetonides were developed. Among seven possible mono- and diketals, six-membered cyclic ketal incorporating the hydroxymethyl group in the 4-position turned out to be the most thermodynamically favorable. The experimental data were consistent with the results of quantum-chemical calculations of the Gibbs energies of formation of different acetonides. The structure of the isolated compounds was studied by X-ray diffraction.

  DOI：

  10.1134/s107042801101012x
• 作为产物：
  描述：

  吡哆醇盐酸盐 在 盐酸 、 sodium methylate 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 135.0h， 生成 3,3,9,9-tetramethyl-7,11-dihydro-1H-[1,3]dioxepino[5,6-b][1,3]dioxino[5,4-d]pyridin-5-ylmethanol
  参考文献：
  名称：

  基于吡ido醇的新型phospho盐的合成及抑菌活性

  摘要：

  在吡x嗪衍生物的基础上合成了13种phospho盐，并在体外测试了它们对临床相关菌株的抗菌活性。所有化合物对革兰氏阴性菌几乎没有活性，对革兰氏阳性菌表现出结构依赖性活性。已证明了缩酮保护基在phospho盐中的抗菌特性至关重要。在合成的化合物中，发现5,6-双[三苯基膦基（甲基）]-2,2,8-三甲基-4 H- [1,3]二氧杂[4,5- c ]吡啶二氯化物（化合物20）是对金黄色葡萄球菌和表皮葡萄球菌最有效菌株（MIC 5μg/ ml）。该化合物的抗菌活性机制可能涉及细胞渗透以及与基因组和质粒DNA的相互作用。

  DOI：

  10.1016/j.bmc.2013.04.051

文献信息

• Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives
  作者：Rail Khaziev、Nikita Shtyrlin、Roman Pavelyev、Raushan Nigmatullin、Raylya Gabbasova、Denis Grishaev、Anna Shtro、Anastasia Galochkina、Yulia Nikolaeva、Tatiana Vinogradova、Olga Manicheva、Marine Dogonadze、Oleg Gnezdilov、Evgenii Sokolovich、Petr Yablonskiy、Konstantin Balakin、Yurii Shtyrlin

  DOI：10.2174/1570180816666190911150705

  日期：2019.11.8

  amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza

  背景：金刚烷衍生物具有多种药理活性，例如抗病毒，抗癌，抗分枝杆菌，抗糖尿病，抗帕金森病等。药物化学家对金刚烷化合物的兴趣是由于其独特的空间结构，高亲脂性和碳笼刚性。结果，这些分子可以容易地穿透生物脂质膜，并且通常具有独特的靶标特异性活性谱。这项工作中研究的另一种药效团是吡ido醇（维生素B6）。吡rid醇作为许多酶的关键辅因子，在活细胞中起着非常重要的作用。另一方面，它的分子支架是一个有价值的结构平台，已导致开发了几种已发布的药物（吡rit醇，皮瑞沙醇，Cycltanine， 目的：本研究的目的是合成吡ido醇-金刚烷和吡ido醇环辛烷双药效团分子。潜在的想法是基于在其结构中具有金刚烷和吡ido醇部分的有希望的抗感染剂的多个实例，来评估这种双药效团的抗菌和抗病毒潜力。另一个特定的原因是探索吡ido醇药效团抑制微生物病原体对药物分子产生耐药性的潜力。 方法：在这项研究中，基于三种不同的环烷基
• Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile
  作者：Marsel R. Garipov、Alina E. Sabirova、Roman S. Pavelyev、Nikita V. Shtyrlin、Svetlana A. Lisovskaya、Oksana V. Bondar、Aleksandr V. Laikov、Julia G. Romanova、Mikhail I. Bogachev、Airat R. Kayumov、Yurii G. Shtyrlin

  DOI：10.1016/j.bioorg.2020.104306

  日期：2020.11

  Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both antifungal and antibacterial activities was designed. The leading compound named KFU-127 exhibits promising antifungal and antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2-4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both fungal and bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of bacterial and fungal-bacterial biofilms.