2-(benzyloxy)-N-(pyridin-3-yl)benzamide

• 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: 2-(benzyloxy)-N-(pyridin-3-yl)benzamide
• 英文别名: 2-phenylmethoxy-N-pyridin-3-ylbenzamide
• 化学式: C₁₉H₁₆N₂O₂
• 分子量: 304.348
• InChiKey: HVBDVJGBSMFSPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(benzyloxy)-N-(pyridin-3-yl)benzamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以98.6%的产率得到2-羟基-N-(3-吡啶基)苯甲酰胺
  参考文献：
  名称：

  EP3196191

  摘要：

  公开号：
• 作为产物：
  描述：

  2-苄氧基苯甲酸 在 吡啶 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 2-(benzyloxy)-N-(pyridin-3-yl)benzamide
  参考文献：
  名称：

  Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor

  摘要：

  The sphingomyelin synthase 2 (SMS2) is a potential target for pharmacological intervention in atherosclerosis. However, so far, few selective SMS2 inhibitors and their pharmacological activities were reported. In this study, a class of 2-benzyloxybenzamides were discovered as novel SMS2 inhibitors through scaffold hopping and structural optimization. Among them, Ly93 as one of the most potent inhibitors exhibited IC50 values of 91 nM and 133.9 mu M against purified SMS2 and SMS1 respectively. The selectivity ratio of Ly93 was more than 1400-fold for purified SMS2 over SMS1. The in vitro studies indicated that Ly93 not only dose-dependently diminished apoB secretion from Huh7 cells, but also significantly reduced the SMS activity and increased cholesterol efflux from macrophages. Meanwhile, Ly93 inhibited the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. The pharmacokinetic profiles of Ly93 performed on C57BL/6J mice demonstrated that Ly93 was orally efficacious. As a potent selective SMS2 inhibitor, Ly93 significantly decreased the plasma SM levels of C57BL/6J mice. Furthermore, Ly93 was capable of dose-dependently attenuating the atherosclerotic lesions in the root and the entire aorta as well as macrophage content in lesions, in apolipoprotein E gene knockout mice treated with Ly93. In conclusion, we discovered a novel selective SMS2 inhibitor Ly93 and demonstrated its anti-atherosclerotic activities in vivo. The preliminary molecular mechanism-of-action studies revealed its function in lipid homeostasis and inflammation process, which indicated that the selective inhibition of SMS2 would be a promising treatment for atherosclerosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.028

文献信息

• 2-ALKYLOXY BENZENE FORMYL ARYLAMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
  申请人：Fudan University

  公开号：EP3196191A1

  公开（公告）日：2017-07-26

  The present invention relates to 2-alkoxy benzene formyl arylamine compounds as scheme I , in which the R, G, X, Y, Z are consistent with the detailed description in the patent claim. The compounds can act as sphingomyelin synthase (SMS) inhibitors to treat diseases caused by abnormal increasing of sphingomyelin(SM). This invention also includes compounds as scheme I , their pharmaceutically acceptable salts, pharmaceutical compositions as the active ingredients, and their application in drugs which can prevent and cure diseases caused by SM level abnormal increase. These diseases include atherosclerosis, fatty liver, obesity, type II diabetes, and other metabolic syndromes.

  本发明涉及如方案 I 所示的 2-烷氧基苯甲酰芳胺化合物，其中 R、G、X、Y、Z 与专利权利要求书中的详细描述一致。这些化合物可作为鞘磷脂合成酶（SMS）抑制剂，用于治疗因鞘磷脂（SM）异常增加而引起的疾病。本发明还包括作为活性成分的方案I化合物、它们的药学上可接受的盐、药物组合物，以及它们在药物中的应用，这些药物可以预防和治疗由SM水平异常升高引起的疾病。这些疾病包括动脉粥样硬化、脂肪肝、肥胖症、II 型糖尿病和其他代谢综合征。
• 2-alkyloxy benzene formyl arylamine compound and pharmaceutical use thereof
  申请人：FUDAN UNIVERSITY

  公开号：US10196359B2

  公开（公告）日：2019-02-05

  2-alkoxy benzene formyl arylamine compounds and their pharmaceutical salts are disclosed. The compounds can act as sphingomyelin synthase (SMS) inhibitors to treat diseases caused by abnormal increasing of sphingomyelin (SM). The pharmaceutically acceptable salts and pharmaceutical compositions of the compounds are used as active ingredients in drugs which can prevent and cure diseases caused by SM level abnormal increase. These diseases include atherosclerosis, fatty liver, obesity, type diabetes, and other metabolic syndromes.

  本研究公开了 2-烷氧基苯甲酰芳胺化合物及其药物盐。这些化合物可作为鞘磷脂合成酶（SMS）抑制剂，治疗因鞘磷脂（SM）异常增加而引起的疾病。这些化合物的药学上可接受的盐和药物组合物可作为药物的活性成分，用于预防和治疗由鞘磷脂水平异常升高引起的疾病。这些疾病包括动脉粥样硬化、脂肪肝、肥胖症、糖尿病和其他代谢综合征。
• EP3196191
  申请人：——

  公开号：——

  公开（公告）日：——
• 2-Alkyloxy benzene formyl arylamine compound and pharmaceutical use thereof
  申请人：FUDAN UNIVERSITY

  公开号：US20170253564A1

  公开（公告）日：2017-09-07

  2-alkoxy benzene formyl arylamine compounds and their pharmaceutical salts are disclosed. The compounds can act as sphingomyelin synthase (SMS) inhibitors to treat diseases caused by abnormal increasing of sphingomyelin (SM). The pharmaceutically acceptable salts and pharmaceutical compositions of the compounds are used as active ingredients in drugs which can prevent and cure diseases caused by SM level abnormal increase. These diseases include atherosclerosis, fatty liver, obesity, type diabetes, and other metabolic syndromes.
• Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor
  作者：Yali Li、Taomin Huang、Bin Lou、Deyong Ye、Xiangyu Qi、Xiaoxia Li、Shuang Hu、Tingbo Ding、Yan Chen、Yang Cao、Mingguang Mo、Jibin Dong、Min Wei、Yong Chu、Huiti Li、Xian-Cheng Jiang、Nengneng Cheng、Lu Zhou

  DOI：10.1016/j.ejmech.2018.12.028

  日期：2019.2

  The sphingomyelin synthase 2 (SMS2) is a potential target for pharmacological intervention in atherosclerosis. However, so far, few selective SMS2 inhibitors and their pharmacological activities were reported. In this study, a class of 2-benzyloxybenzamides were discovered as novel SMS2 inhibitors through scaffold hopping and structural optimization. Among them, Ly93 as one of the most potent inhibitors exhibited IC50 values of 91 nM and 133.9 mu M against purified SMS2 and SMS1 respectively. The selectivity ratio of Ly93 was more than 1400-fold for purified SMS2 over SMS1. The in vitro studies indicated that Ly93 not only dose-dependently diminished apoB secretion from Huh7 cells, but also significantly reduced the SMS activity and increased cholesterol efflux from macrophages. Meanwhile, Ly93 inhibited the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. The pharmacokinetic profiles of Ly93 performed on C57BL/6J mice demonstrated that Ly93 was orally efficacious. As a potent selective SMS2 inhibitor, Ly93 significantly decreased the plasma SM levels of C57BL/6J mice. Furthermore, Ly93 was capable of dose-dependently attenuating the atherosclerotic lesions in the root and the entire aorta as well as macrophage content in lesions, in apolipoprotein E gene knockout mice treated with Ly93. In conclusion, we discovered a novel selective SMS2 inhibitor Ly93 and demonstrated its anti-atherosclerotic activities in vivo. The preliminary molecular mechanism-of-action studies revealed its function in lipid homeostasis and inflammation process, which indicated that the selective inhibition of SMS2 would be a promising treatment for atherosclerosis. (C) 2018 Elsevier Masson SAS. All rights reserved.