4-methoxy-3-octyloxybenzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-methoxy-3-octyloxybenzoic acid
• 英文别名: 4-Methoxy-3-octoxybenzoic acid
• 化学式: C₁₆H₂₄O₄
• 分子量: 280.364
• InChiKey: QNWKMCRFIDDLKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methoxy-3-octyloxybenzoic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 、 盐酸羟胺 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 3.08h， 生成 N-hydroxy-4-methoxy-3-(octyloxy)benzamide
  参考文献：
  名称：

  Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model

  摘要：

  Acid sphingomyelinase (ASM) has been shown to be involved in many physiological processes, emerging to be a promising drug target. In this study, we constructed a ligand-based pharmacophore model of ASM inhibitors and applied this model to optimize the lead compound alpha-mangostin, a known inhibitor of ASM. 23 compounds were designed and evaluated in vitro for ASM inhibition, of these, 10 compounds were found to be more potent than alpha-mangostin. This high hit ratio confirmed that the presented model is very effective and practical. The most potent hit, 1c, was found to selectively and competitively inhibit the enzyme and inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with key residues and the Zn2+ cofactor of 1c were found by docking simulation. These results provide promising leads and important guidance for further development of efficient ASM inhibitors and drug candidates. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.065
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯甲酸甲酯 在 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 11.0h， 生成 4-methoxy-3-octyloxybenzoic acid
  参考文献：
  名称：

  一种酸性鞘磷脂酶抑制剂及其在相关疾病中 的应用

  摘要：

  本发明属于药物化学领域，具体涉及酸性鞘磷脂酶。本发明提供了酸性鞘磷脂酶的抑制剂，具体结构为式I所示。本发明还提供了式I所示的合成方法及其在与细胞凋亡和炎症相关的疾病中的应用，包括动脉粥样硬化(AS)、糖尿病、肺气肿、肺水肿、肺部纤维化、囊性纤维化、非酒精性脂肪肝、阿尔兹海默(AD)、多发性硬化症(MS)、脑卒中、抑郁症。

  公开号：

  CN108250105B

文献信息

• 一种酸性鞘磷脂酶抑制剂及其在相关疾病中 的应用
  申请人：中国药科大学

  公开号：CN108250105B

  公开（公告）日：2021-07-16

  本发明属于药物化学领域，具体涉及酸性鞘磷脂酶。本发明提供了酸性鞘磷脂酶的抑制剂，具体结构为式I所示。本发明还提供了式I所示的合成方法及其在与细胞凋亡和炎症相关的疾病中的应用，包括动脉粥样硬化(AS)、糖尿病、肺气肿、肺水肿、肺部纤维化、囊性纤维化、非酒精性脂肪肝、阿尔兹海默(AD)、多发性硬化症(MS)、脑卒中、抑郁症。
• Berdague, Philippe; Perez, Felix; Courtieu, Jacques, Bulletin de la Societe Chimique de France, 1994, vol. 131, # 3, p. 335 - 343
  作者：Berdague, Philippe、Perez, Felix、Courtieu, Jacques、Bayle, Jean-Pierre

  DOI：——

  日期：——
• Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model
  作者：Kan Yang、Keyi Nong、Qinlan Gu、Jibin Dong、Jinxin Wang

  DOI：10.1016/j.ejmech.2018.03.065

  日期：2018.5

  Acid sphingomyelinase (ASM) has been shown to be involved in many physiological processes, emerging to be a promising drug target. In this study, we constructed a ligand-based pharmacophore model of ASM inhibitors and applied this model to optimize the lead compound alpha-mangostin, a known inhibitor of ASM. 23 compounds were designed and evaluated in vitro for ASM inhibition, of these, 10 compounds were found to be more potent than alpha-mangostin. This high hit ratio confirmed that the presented model is very effective and practical. The most potent hit, 1c, was found to selectively and competitively inhibit the enzyme and inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with key residues and the Zn2+ cofactor of 1c were found by docking simulation. These results provide promising leads and important guidance for further development of efficient ASM inhibitors and drug candidates. (C) 2018 Elsevier Masson SAS. All rights reserved.