4-[2-Chloro-4-(trifluoromethyl)phenoxy]benzaldehyde | 71108-60-6

• 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: 4-[2-Chloro-4-(trifluoromethyl)phenoxy]benzaldehyde
• CAS: 71108-60-6
• 化学式: C₁₄H₈ClF₃O₂
• 分子量: 300.665
• InChiKey: KWDFDWBVSLBKDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[2-Chloro-4-(trifluoromethyl)phenoxy]benzaldehyde 在 palladium on carbon 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 methyl 3-(4-(2-chloro-4-(trifluoromethyl)phenoxy)phenyl)propanoate
  参考文献：
  名称：

  3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists

  摘要：

  The design, synthesis, and structure-activity relationship (SAR) for a series of beta-substituted 3-(4-aryloxyaryl) propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.114
• 作为产物：
  描述：

  3-氯-4-氟三氟甲苯 、 对羟基苯甲醛 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-[2-Chloro-4-(trifluoromethyl)phenoxy]benzaldehyde
  参考文献：
  名称：

  3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists

  摘要：

  The design, synthesis, and structure-activity relationship (SAR) for a series of beta-substituted 3-(4-aryloxyaryl) propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.114

文献信息

• Discovery of Novel Cytochrome bc1 Complex Inhibitor Based on Natural Product Neopeltolide
  作者：Tao Chen、Rui Zhang、Yu-Xia Wang、Meng-Qi Gao、Qiong Chen、Xiao-Lei Zhu、Guang-Fu Yang

  DOI：10.2174/1570180818666211006142034

  日期：2022.4

  Natural products (NPs) are important sources for the design of new drugs and agrochemicals. Neopeltolide, a marine NP, has been identified as a potent Qo-site inhibitor of cytochrome bc1 complex.

  In this study, a series of neopeltolide derivatives was designed and synthesized by the simplification of its 14-membered macrolactone ring with a diphenyl ether fragment. The enzymatic inhibition bioassays and mycelium growth inhibition experiments against a range of fungi were performed to determine their fungicidal activities.

  The derivatives have potent activity against the porcine bc1 complex. Compound 8q showed the best activity with an IC50 value of 24.41 nM, which was 8-fold more effective than that of positive control azoxystrobin. Compound 8a exhibited a 100% inhibitory rate against Zymoseptoria tritici and Alternaria solani at a 20 mg/L dose.

  Computational results indicated that compounds with suitable physicochemical properties, as well as those forming a hydrogen bond with His161, would have good fungicidal activity. These data could be useful for the design of bc1 complex inhibitors in the future.

  背景：天然产物（NPs）是设计新药物和农药的重要来源。海洋天然产物新皮尔酮已被鉴定为细胞色素bc1复合物的有效Qo-位点抑制剂。 方法：本研究通过简化新皮尔酮14元大环内酯环并加入二苯醚基团，设计并合成了一系列新皮尔酮衍生物。采用酶抑制生物测定和对一系列真菌的菌丝生长抑制实验来确定它们的杀真菌活性。 结果：这些衍生物对猪bc1复合物具有强大的活性。化合物8q表现出最佳活性，其IC50值为24.41 nM，比阳性对照阿托霉素有效成分的效果高8倍。化合物8a在20 mg/L剂量下对小麦条锈菌和茄根黑斑病菌表现出100%的抑制率。 结论：计算结果表明，具有适当物理化学性质以及与His161形成氢键的化合物将具有良好的杀真菌活性。这些数据对未来设计bc1复合物抑制剂可能会有用。
• US4287213A
  申请人：——

  公开号：US4287213A

  公开（公告）日：1981-09-01
• 3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists
  作者：Shawn P. Walsh、Alexandra Severino、Changyou Zhou、Jiafang He、Gui-Bai Liang、Carina P. Tan、Jin Cao、George J. Eiermann、Ling Xu、Gino Salituro、Andrew D. Howard、Sander G. Mills、Lihu Yang

  DOI：10.1016/j.bmcl.2011.03.114

  日期：2011.6

  The design, synthesis, and structure-activity relationship (SAR) for a series of beta-substituted 3-(4-aryloxyaryl) propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model. (C) 2011 Elsevier Ltd. All rights reserved.