(4,5-bis((4-methoxybenzyl)oxy)pyridin-2-yl)methanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4,5-bis((4-methoxybenzyl)oxy)pyridin-2-yl)methanol
• 英文别名: 6-hydroxymethyl-3,4-bis[(p-methoxybenzyl)oxy]-pyridine；[4,5-bis[(4-methoxyphenyl)methoxy]pyridin-2-yl]methanol
• 化学式: C₂₂H₂₃NO₅
• 分子量: 381.428
• InChiKey: HDQDZFYBTMLGBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 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：

  (4,5-bis((4-methoxybenzyl)oxy)pyridin-2-yl)methanol 在 三氧化硫吡啶 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 9.5h， 生成 2-(1-((1,3-dioxoisoindolin-2-yl)oxy)-2-isopropoxyethyl)-4,5-bis((4-methoxybenzyl)oxy)pyridine 1-oxide
  参考文献：
  名称：

  Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections

  摘要：

  Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated mono-sulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4(1H)-one and the aminothiazole oxime were designed and synthesized. Structure activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound 12c) and methylthiomethyl (compound 16a) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound 12c exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound 12c shows an ED50 of 10.20 mg/kg. Taken together, the results indicate that compound 12c is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens.

  DOI：

  10.1021/acs.jmedchem.6b01261
• 作为产物：
  描述：

  曲酸 在 ammonium hydroxide 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 (4,5-bis((4-methoxybenzyl)oxy)pyridin-2-yl)methanol
  参考文献：
  名称：

  在C-14侧链上被4H-吡喃-4-酮和吡啶-4-酮取代的新型截短侧耳素衍生物的设计，合成和抗菌活性

  摘要：

  摘要设计合成了一系列新颖的截短侧耳素衍生物，其在C-14侧链上具有4个H-吡喃-4-酮和吡啶-4-酮取代基。体外抗菌活性评估表明，大多数衍生物对耐药革兰氏阳性菌株均表现出有效的抗菌活性。化合物12a，12d和28是该系列中活性最高的衍生物，其活性与雷帕米林和BC-3781相当。由于该系列的代谢稳定性不令人满意，因此正在进行进一步的修饰以改善其药代动力学特性。

  DOI：

  10.1016/j.cclet.2015.09.019

文献信息

• [EN] HETEROBICYCLIC COMPOUNDS AS BETA-LACTAMASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROBICYCLIQUES COMME INHIBITEURS DE LA BÊTA-LACTAMASE
  申请人：ASTRAZENECA AB

  公开号：WO2013150296A1

  公开（公告）日：2013-10-10

  The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts, are useful in combination with beta-lactam antibiotics, or alone, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to formula (Ia): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R 2, R 3 and R 4 are described herein.

  本发明涉及一种β-内酰胺酶抑制剂化合物。这些化合物及其药学上可接受的盐，可与β-内酰胺类抗生素结合使用，或单独使用，用于治疗细菌感染，包括由耐药菌株引起的感染，包括多药耐药菌株引起的感染。本发明包括根据式(Ia)的化合物：或其药学上可接受的盐，其中R1、R2、R3和R4的值如本文所述。
• Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with 4 H -pyran-4-one and pyridin-4-one substitution in the C-14 side chain
  作者：Chen-Yu Ling、Yun-Liang Tao、Wen-Jing Chu、Hui Wang、Hai-Dong Wang、Yu-She Yang

  DOI：10.1016/j.cclet.2015.09.019

  日期：2016.2

  H -pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a , 12d , and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin

  摘要设计合成了一系列新颖的截短侧耳素衍生物，其在C-14侧链上具有4个H-吡喃-4-酮和吡啶-4-酮取代基。体外抗菌活性评估表明，大多数衍生物对耐药革兰氏阳性菌株均表现出有效的抗菌活性。化合物12a，12d和28是该系列中活性最高的衍生物，其活性与雷帕米林和BC-3781相当。由于该系列的代谢稳定性不令人满意，因此正在进行进一步的修饰以改善其药代动力学特性。
• Cephem compounds and anti-bacterial agent
  申请人：Meiji Seika Kabushiki Kaisha

  公开号：US04988686A1

  公开（公告）日：1991-01-29

  Disclosed is a novel cephem compound which is either one of a cis- or trans-isomer or a mixture of the cis-and trans-isomers, represented by the following general formula (I) and a pharmacologically acceptable salt thereof: ##STR1## wherein all of the substituents are as defined hereinbefore. Also disclosed are a process for producing the above compound and its use as an anti-bacterial agent comprising the same.

  本文披露了一种新的头孢菌素化合物，其为顺式或反式异构体中的一种，或者为顺式和反式异构体的混合物，其表示为以下一般式（I）及其药理上可接受的盐：##STR1## 其中所有的取代基均如前文所定义。还披露了生产上述化合物的方法以及其作为抗菌剂的用途。
• Cephalosporin derivatives and antibacterial agents
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04918070A1

  公开（公告）日：1990-04-17

  A cephalosporin derivative having the formula: ##STR1## wherein R.sup.1 is a substituted amino group, X is an alkylene group, R.sup.2 is an aryl or heterocyclic group which may be substituted and R.sup.3 is a hydrogen atom, a negative charge or a residue of an ester which can form a pharmaceutically acceptable ester hydrolyzable in a living body; or a pharmaceutically acceptable salt thereof.

  一种头孢菌素衍生物，其化学式为： ##STR1## 其中R.sup.1是一个取代的氨基团，X是一个烷基团，R.sup.2是一个可能被取代的芳基或杂环基团，R.sup.3是一个氢原子，一个负电荷或能够在生物体内水解的酯的残基，该酯可以形成一种药学上可接受的酯；或其药学上可接受的盐。
• Cephalosporin derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US05049665A1

  公开（公告）日：1991-09-17

  A cephalosporin derivative having the formula: ##STR1## wherein R.sup.1 is a substituted amino group, X is an alkylene group, R.sup.2 is an aryl or heterocyclic group which may be substituted and R.sup.3 is a hydrogen atom, a negative charge or a residue of an ester which can form a pharmaceutically acceptable ester hydrolyzable in a living body; or a pharmaceutically acceptable salt thereof.

  一种头孢菌素衍生物，其化学式为：##STR1##其中R.sup.1是取代的氨基团，X是烷基团，R.sup.2是可能被取代的芳基或杂环基团，R.sup.3是氢原子、负电荷或可以在活体内水解的药用可接受酯的残基；或其药用可接受盐。