3,4-dihydroxy-N-(4-(trifluoromethyl)benzyl)benzamide | 1609176-89-7

• 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: 3,4-dihydroxy-N-(4-(trifluoromethyl)benzyl)benzamide
• 英文别名: 3,4-dihydroxy-N-[[4-(trifluoromethyl)phenyl]methyl]benzamide
• CAS: 1609176-89-7
• 化学式: C₁₅H₁₂F₃NO₃
• 分子量: 311.26
• InChiKey: BUEQPUWQJBHVSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  原儿茶酸 、 4-(三氟甲基)苄胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以52 %的产率得到3,4-dihydroxy-N-(4-(trifluoromethyl)benzyl)benzamide
  参考文献：
  名称：

  Hydroxybenzamide derivatives protect pancreatic β cell by suppressing unfolded protein response activation

  摘要：

  AbstractEndoplasmic reticulum (ER) stress‐induced Pancreatic β‐cell dysfunction and death plays important roles in the development of diabetes. The 1,2,3‐triazole derivative 1 is one of only a few structures that have thus far been identified that protect β cells against ER stress, but it is limited for its narrow activity range. In this study, we designed and synthesized a series of hydroxybenzamide (HBA) derivatives in which the triazole pharmacophore was substituted with an amide linker. Structure–activity relationship studies identified WO3i (3‐hydroxy‐N‐(4‐[trifluoromethyl]benzyl)benzamide) that possesses β‐cell protective activity against ER stress at a 100% maximal activity with EC50 at 0.19 μM). We showed that WO3i suppresses the expression of CHOP, a key mediator of ER stress‐induced apoptosis, and the activation of apoptotic genes. Mechanistically, we further showed that WO3i suppresses the ER stress‐induced activation of all three pathways of unfolded protein response—ATF6, IRE1α, and PERK. Identification of this novel β‐cell‐protective scaffold thus provides a new promising modality for the potential for drug development for the treatment of diabetes.

  DOI：

  10.1111/cbdd.14093

文献信息

• [EN] PLASMINOGEN ACTIVATOR-1 INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE L'ACTIVATEUR 1 DU PLASMINOGÈNE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV MICHIGAN

  公开号：WO2014070983A1

  公开（公告）日：2014-05-08

  The invention relates to plasminogen activator- 1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

  本发明涉及纤溶酶原激活剂-1（PAI-1）抑制剂化合物及其在治疗与PAI-1水平升高相关的任何疾病或失调症中的用途。发明包括但不限于使用这些化合物来预防或减少血栓形成和纤维化，促进血栓溶解，以及调节脂质代谢和治疗与PAI-1、胆固醇或脂质水平升高相关的疾病或失调症。
• PLASMINOGEN ACTIVATOR INHIBITOR-1 INHIBITORS AND METHODS OF USE THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20150315178A1

  公开（公告）日：2015-11-05

  The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

  本发明涉及纤溶酶原激活剂-1（PAI-1）抑制剂化合物及其在治疗任何与高PAI-1相关的疾病或障碍中的应用。本发明包括但不限于使用这些化合物来预防或减少血栓形成和纤维化，促进溶栓，调节脂质代谢并治疗与高PAI-1，胆固醇或脂质水平相关的疾病或障碍。
• PLASMINOGEN ACTIVATOR-1 INHIBITORS AND METHODS OF USE THEREOF
  申请人：The Regents of The University of Michigan

  公开号：EP2914575B1

  公开（公告）日：2020-10-14
• US9718760B2
  申请人：——

  公开号：US9718760B2

  公开（公告）日：2017-08-01