4-[3-(2-quinolinylmethoxy)phenoxy]butyric acid | 125439-17-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-[3-(2-quinolinylmethoxy)phenoxy]butyric acid
• 英文别名: 4-[3-(Quinolin-2-ylmethoxy)-phenoxy]-butyric acid；4-[3-(quinolin-2-ylmethoxy)phenoxy]butanoic acid
• CAS: 125439-17-0
• 化学式: C₂₀H₁₉NO₄
• 分子量: 337.375
• InChiKey: HYTBIVFDTLBKQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-[3-(Quinolin-2-ylmethoxy)-phenoxy]-butyric acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以55%的产率得到4-[3-(2-quinolinylmethoxy)phenoxy]butyric acid
  参考文献：
  名称：

  Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships

  摘要：

  This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

  DOI：

  10.1021/jm00166a016

文献信息

• Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease
  作者：Stefano Fiorucci、Pasquale Rapacciuolo、Bianca Fiorillo、Rosalinda Roselli、Silvia Marchianò、Cristina Di Giorgio、Martina Bordoni、Rachele Bellini、Chiara Cassiano、Paolo Conflitti、Bruno Catalanotti、Vittorio Limongelli、Valentina Sepe、Michele Biagioli、Angela Zampella

  DOI：10.3389/fphar.2022.858137

  日期：——

  clinical need. Here, we report the discovery of a novel class of hybrid molecules designed to function as cysteinyl leukotriene receptor 1 (CysLT1R) antagonists and G protein bile acid receptor 1 (GPBAR1/TGR5) agonists for the treatment of NAFLD/NASH. The most potent of these compounds generated by harnessing the scaffold of the previously described CystLT1R antagonists showed efficacy in reversing liver

  非酒精性脂肪性肝病 (NAFLD) 和非酒精性脂肪性肝炎 (NASH) 是由肝脏中过多的脂肪沉积引起的两种高度流行的人类疾病。尽管已经提出了多种方法，但 NAFLD/NASH 仍然是未满足的临床需求。在这里，我们报告了一种新型混合分子的发现，该分子被设计用作半胱氨酰白三烯受体 1 (CysLT 1 R) 拮抗剂和 G 蛋白胆汁酸受体 1 (GPBAR1/TGR5) 激动剂，用于治疗 NAFLD/NASH。通过利用先前描述的 CystLT 1的支架产生的这些化合物中最有效的R 拮抗剂在 NASH 临床前模型中显示出逆转肝脏组织病理学特征、重塑肝脏转录组以及肝脏和脂肪组织中的脂质和能量代谢的功效。总之，本研究描述了一种新型口服活性双 CysLT 1 R 拮抗剂/GPBAR1 激动剂，可有效防止 NAFLD/NASH 的发展，显示出进一步发展的前景。
• YOUSSEFYEH, RAYMOND D.;MAGNIEN, ERNEST;LEE, THOMAS D. Y.;CHAN, WAN-KIT;LI+, J. MED. CHEM., 33,(1990) N, C. 1186-1194
  作者：YOUSSEFYEH, RAYMOND D.、MAGNIEN, ERNEST、LEE, THOMAS D. Y.、CHAN, WAN-KIT、LI+

  DOI：——

  日期：——
• USRE40558E1
  申请人：——

  公开号：USRE40558E1

  公开（公告）日：2008-10-28