2-(羟甲基)-5-[(4-甲氧基苯基)甲氧基]-1H-吡啶-4-酮 | 118679-90-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-(羟甲基)-5-[(4-甲氧基苯基)甲氧基]-1H-吡啶-4-酮
• 英文名称: 2-(hydroxymethyl)-5-((4-methoxybenzyl)oxy)pyridin-4(1H)-one
• 英文别名: 2-(hydroxymethyl)-5-[(4-methoxyphenyl)methoxy]-1H-pyridin-4-one
• CAS: 118679-90-6
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: GMSCKKIRAYIIAL-UHFFFAOYSA-N

物化性质

• 沸点：
  496.8±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(羟甲基)-5-[(4-甲氧基苯基)甲氧基]-1H-吡啶-4-酮 在 三氧化硫吡啶 、 sodium hydride 、 potassium carbonate 、 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 9.0h， 生成 2-(1-((1,3-dioxoisoindolin-2-yl)oxy)-2-methoxyethyl)-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 20.0h， 生成 2-(羟甲基)-5-[(4-甲氧基苯基)甲氧基]-1H-吡啶-4-酮
  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

• Cephalosporins, processes for their preparation and pharmaceutical compositions containing them
  申请人：BEECHAM GROUP PLC

  公开号：EP0265185A3

  公开（公告）日：1990-03-28

  Antibacterial agents have the formula (Ia) or are pharmaceutically acceptable salts or invivo hydrolysable esters thereof: wherein R¹ is an acyl group, in particular that of an antibacterially active cephalosporin; R² is hydrogen, methoxy, or formamido; Y is S, SO, SO₂, O or CH₂; X is oxygen, sulphur, or -NH- and R⁴ is a group of the formula CO Z R⁵ wherein Z is -CH=CH-, -(CH₂)n- or -NH-; n is 0, 1 or 2; and R⁵ is: wherein R⁶ and R⁷ are the same or different, each representing hydroxy or protected hydroxy and R⁸ is hydroxy, amino, halogen or carboxy.The use of the compounds of formula (Ia) and intermediates for their preparation are also disclosed.

  抗菌剂的化学式为（Ia），或者是其药用可接受的盐或体内水解酯： 其中R¹是酰基，特别是抗菌活性头孢菌素的酰基；R²是氢、甲氧基或甲酰胺基；Y是S、SO、SO₂、O或CH₂；X是氧、硫或-NH-，R⁴是化学式CO Z R⁵的基团，其中Z是-CH=CH-、-(CH₂)n-或-NH-；n为0、1或2；R⁵是： 其中R⁶和R⁷相同或不同，分别代表羟基或保护羟基，R⁸是羟基、氨基、卤素或羧基。该化合物的使用和其制备的中间体也被披露。
• [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。
• CARBINOL DERIVATIVES HAVING HETEROCYCLIC LINKER
  申请人：Koura Minoru

  公开号：US20100280013A1

  公开（公告）日：2010-11-04

  [Object] It is to provide a novel LXRβ agonist useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. [Solving Means] A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate: (wherein, each V and W independently show N or C—R 7 ; each X and Y independently show CH 2 , C═O, SO 2 , etc; Z shows CH or N; each R 1 , R 2 and R 7 independently show a hydrogen atom, C 1-8 alkyl group, etc.; R 3 shows C 1-8 alkyl group; R 4 shows an optionally substituted C 6-10 aryl group or an optionally substituted 5- to 11-membered heterocyclic group; R 5 and R 6 show a hydrogen atom, etc.; L shows a C 1-8 alkyl chain optionally substituted with an oxo group, etc.; and n shows any integer of 0 to 2.)

  它是提供一种新型的LXRβ激动剂，可用作预防和/或治疗动脉粥样硬化；动脉硬化，如由糖尿病引起的动脉硬化；血脂异常；高胆固醇血症；与脂质相关的疾病；由炎性细胞因子引起的炎症性疾病；过敏性皮肤病；糖尿病；或阿尔茨海默病的预防和/或治疗剂。【解决手段】由以下一般式（I）表示的羟甲基化合物或其盐，或它们的溶剂化合物： （其中，每个V和W独立地表示N或C—R 7 ；每个X和Y独立地表示CH 2 ，C═O，SO 2 等；Z表示CH或N；每个R 1 ，R 2 和R 7 独立地表示氢原子，C 1-8 烷基基团等；R 3 表示C 1-8 烷基基团；R 4 表示可选择地取代的C 6-10 芳基基团或可选择地取代的5-至11-成员杂环基团；R 5 和R 6 表示氢原子等；L表示可选择地取代有氧基团等的C 1-8 烷基链；n表示0至2的任意整数。】
• 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。
• Antibacterial agents
  申请人：Axten MICHAEL Jeffrey

  公开号：US20060041123A1

  公开（公告）日：2006-02-23

  Quinoline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans.

  喹啉和萘啶衍生物可用于治疗哺乳动物（尤其是人类）的细菌感染。