1-(4-fluorobenzoyl)-4-hydroxy-3-propylbenzene | 874988-14-4

• 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: 1-(4-fluorobenzoyl)-4-hydroxy-3-propylbenzene
• 英文别名: (4-fluorophenyl)(4-hydroxy-3-propylphenyl)methanone；(4-Fluorophenyl)-(4-hydroxy-3-propylphenyl)methanone
• CAS: 874988-14-4
• 化学式: C₁₆H₁₅FO₂
• 分子量: 258.292
• InChiKey: FZCJCDGORFBSAL-UHFFFAOYSA-N

物化性质

• 沸点：
  413.0±45.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorobenzoyl)-4-hydroxy-3-propylbenzene 在 lithium hydroxide 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (5-{3-[4-(4-fluoro-benzoyl)-2-propyl-phenoxy]-propoxy}-indol-1-yl)-acetic acid
  参考文献：
  名称：

  Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists:  Design, Synthesis, Structural Biology, and Molecular Docking Studies

  摘要：

  A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPAR gamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPAR gamma protein resulting in potent activity.

  DOI：

  10.1021/jm0510373
• 作为产物：
  描述：

  (3-Allyl-4-hydroxy-phenyl)-(4-fluoro-phenyl)-methanone 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以0.496 g的产率得到1-(4-fluorobenzoyl)-4-hydroxy-3-propylbenzene
  参考文献：
  名称：

  Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists:  Design, Synthesis, Structural Biology, and Molecular Docking Studies

  摘要：

  A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPAR gamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPAR gamma protein resulting in potent activity.

  DOI：

  10.1021/jm0510373

文献信息

• Structural Basis for the Improved Potency of Peroxisome Proliferator-Activated Receptor (PPAR) Agonists
  作者：Yi-Hui Peng、Mohane Selvaraj Coumar、Jiun-Shyang Leou、Jian-Sung Wu、Hui-Yi Shiao、Chia-Hui Lin、Wen-Hsing Lin、Tzu Wen Lien、Xin Chen、John T.-A. Hsu、Yu-Sheng Chao、Chien-Fu Huang、Ping-Chiang Lyu、Hsing-Pang Hsieh、Su-Ying Wu

  DOI：10.1002/cmdc.201000194

  日期：——

  antidiabetic drugs is essential owing to the growth worldwide of the diabetic population. Targeting the PPAR receptor is one strategy for the treatment of diabetes; the PPAR agonists rosiglitazone and pioglitazone are already on the market. Here we report the identification of a potent PPAR agonist, 15, whose PPARγ activation was more than 20 times better than that of rosiglitazone. Compound 15 was designed

  由于世界范围内糖尿病患者的增长，开发更安全，更有效的抗糖尿病药物至关重要。靶向PPAR受体是治疗糖尿病的一种策略。PPAR激动剂罗格列酮和吡格列酮已经投放市场。在这里，我们报告了一种有效的PPAR激动剂15的鉴定，该激动剂的PPARγ活化比罗格列酮强20倍以上。化合物15设计为结合具有羧酸基团的吲哚头和4-苯基二苯甲酮尾，以实现10 n M的PPARγEC 50。化合物15在我们研究的化合物中显示出最有效的PPARγ激动剂活性。为了获得分子对提高15效力的见解，进行了结构生物学研究和结合能计算。15和激动剂10的X射线结构的叠加表明，即使它们具有相同的吲哚头部，它们也采用不同的构象。15的头部显示出与PPARγ的更强相互作用。这可能是由于存在新型的尾巴部分4-苯基二苯甲酮，可以提高15与PPARγ的结合效率。
• COMPOUNDS FOR TREATING PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) MEDIATED DISEASES OR CONDITIONS
  申请人：MEDIPURE PHARMACEUTICALS INC.

  公开号：US20220378744A1

  公开（公告）日：2022-12-01

  Novel compounds, in particular novel peroxisome proliferator-activated receptor (PPAR) agonist compounds, are provided. Pharmaceutical formulations for treating PPAR mediated disorder or condition are also provided. The formulations may be a combination of cannabinoids and the PPAR agonist compounds. The PPAR mediated disorder or condition may include inflammation related diseases such as psoriasis, psoriatic arthritis and atopic dermatitis.

  提供了新型化合物，特别是新型过氧化物酶体增殖物激活受体（PPAR）激动剂化合物。还提供了用于治疗PPAR介导的疾病或症状的制药配方。这些配方可以是大麻素和PPAR激动剂化合物的组合。PPAR介导的疾病或症状可能包括与炎症相关的疾病，如牛皮癣、银屑病性关节炎和特应性皮炎。
• Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor γ Agonists
  作者：Chia-Hui Lin、Yi-Hui Peng、Mohane Selvaraj Coumar、Santhosh Kumar Chittimalla、Chun-Chen Liao、Ping-Chiang Lyn、Chin-Chieh Huang、Tzu-Wen Lien、Wen-Hsing Lin、John T.-A. Hsu、Jai-Hong Cheng、Xin Chen、Jian-Sung Wu、Yu-Sheng Chao、Hwei-Jen Lee、Chiun-Gung Juo、Su-Ying Wu、Hsing-Pang Hsieh

  DOI：10.1021/jm801594x

  日期：2009.4.23

  Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.
• [EN] COMPOUNDS FOR TREATING PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) MEDIATED DISEASES OR CONDITIONS<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE MALADIES OU D'ÉTATS PATHOLOGIQUES INDUITS PAR LES RÉCEPTEURS ACTIVÉS PAR LES PROLIFÉRATEURS DE PEROXYSOMES (PPAR)
  申请人：[en]MEDIPURE PHARMACEUTICALS INC.

  公开号：WO2022221960A1

  公开（公告）日：2022-10-27

  Novel compounds, in particular novel peroxisome proliferator-activated receptor (PPAR) agonist compounds, are provided. Pharmaceutical formulations for treating PPAR mediated disorder or condition are also provided. The formulations may be a combination of cannabinoids and the PPAR agonist compounds. The PPAR mediated disorder or condition may include inflammation related diseases such as psoriasis, psoriatic arthritis and atopic dermatitis.