1-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)-3-(naphthalen-1-yl)urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)-3-(naphthalen-1-yl)urea
• 英文别名: 1-(5-Hydroxy-3,4,6-trimethylpyridin-2-yl)-3-naphthalen-1-ylurea；1-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)-3-naphthalen-1-ylurea
• 化学式: C₁₉H₁₉N₃O₂
• 分子量: 321.379
• InChiKey: UOMJEWIKFNRSHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  74.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-(benzyloxy)-3,4,6-trimethylpyridin-2-amine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 1-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)-3-(naphthalen-1-yl)urea
  参考文献：
  名称：

  Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells

  摘要：

  Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 mu M concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.046

文献信息

• Pyridinol derivative or pharmaceutically acceptable salt thereof, and pharmaceutical composition containing same as active ingredient
  申请人：Research Cooperation Foundation of Yeungnam University

  公开号：US10604487B2

  公开（公告）日：2020-03-31

  The present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, containing, as an active ingredient, a pyridinol derivative or a pharmaceutically acceptable salt thereof. A pyridinol derivative represented by chemical formula 1 or a pharmaceutically acceptable salt thereof has an excellent colitis inhibitory effect in an inflammatory bowel disease model, and thus can be useful as a medicine for preventing or treating inflammatory bowel disease.

  本发明涉及一种用于预防或治疗炎症性肠病的药物组合物，其活性成分含有吡啶醇衍生物或其药学上可接受的盐。化学式 1 所代表的吡啶醇衍生物或其药学上可接受的盐在炎症性肠病模型中具有极佳的结肠炎抑制效果，因此可用作预防或治疗炎症性肠病的药物。
• PYRIDINOL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Research Cooperation Foundation of Yeungnam University

  公开号：EP3404020B1

  公开（公告）日：2022-11-30
• [EN] PYRIDINOL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT<br/>[FR] DÉRIVÉ DE PYRIDINOL OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, ET COMPOSITION PHARMACEUTIQUE CONTENANT CELUI-CI UTILISÉ COMME PRINCIPE ACTIF<br/>[KO] 피리딘올 유도체 또는 이의 약제학적 허용 가능한 염 및 이를 유효성분으로 함유하는 약학 조성물
  申请人：UNIV YEUNGNAM RES COOPERATION FOUNDATION

  公开号：WO2017123038A1

  公开（公告）日：2017-07-20

  본 발명은 피리딘올 유도체 또는 이의 약제학적 허용가능한 염을 유효성분으로 함유하는 염증성 장질환의 예방 또는 치료용 약학조성물에 관한 것으로, 화학식 1로 표시되는 피리딘올 유도체 또는 이의 약제학적 허용가능한 염은 염증성 장질환 모델에서의 대장염 억제 효과가 탁월하여, 염증성 장질환의 예방 또는 치료용 약제로서 유용하게 사용될 수 있다.
• [EN] PYRIDINOL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING AUTOIMMUNE DISEASES, CONTAINING SAME AS ACTIVE INGREDIENT<br/>[FR] DÉRIVÉ DE PYRIDINOL OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CE DERNIER, ET COMPOSITION PHARMACEUTIQUE POUR PRÉVENIR OU TRAITER DES MALADIES AUTOIMMUNES CONTENANT CE DERNIER EN TANT QUE PRINCIPE ACTIF<br/>[KO] 피리딘올 유도체 또는 이의 약제학적 허용 가능한 염 및 이를 유효성분으로 함유하는 자가면역 질환의 예방 또는 치료용 약학 조성물
  申请人：UNIV YEUNGNAM RES COOPERATION FOUNDATION

  公开号：WO2018131924A1

  公开（公告）日：2018-07-19

  본 발명은 피리딘올 유도체 또는 이의 약제학적 허용가능한 염을 유효성분으로 함유하는 자가면역 질환의 예방 또는 치료용 약학 조성물에 관한 것다. 화학식 1로 표시되는 피리딘올 유도체 또는 이의 약제학적 허용가능한 염은 염증 T 세포인 Th1 및 Th17 세포의 분화를 억제하고, 그 세포들의 염증 사이토카인 분비를 탁월하게 억제하여 질환의 진행을 완화시킬 수 있다. 또한, 면역을 억제하는 Treg 세포에는 영향을 주지 않고 염증 T 세포에만 특이적으로 작용함으로, 자가면역 질환의 예방 또는 치료용 약제로서 유용하게 사용할 수 있다.
• Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells
  作者：Dawon Bae、Jaya Gautam、Hyeonjin Jang、Suhrid Banskota、Sang Yeul Lee、Min-Ji Jeong、A-Sol Kim、Hong Chul Kim、Iyn-Hyang Lee、Tae-gyu Nam、Jung-Ae Kim、Byeong-Seon Jeong

  DOI：10.1016/j.bmcl.2017.11.046

  日期：2018.1

  Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 mu M concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics. (C) 2017 Elsevier Ltd. All rights reserved.