methyl N-(3-phenoxypropionoyl)anthranilate | 6047-28-5

• 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: methyl N-(3-phenoxypropionoyl)anthranilate
• 英文别名: methyl N-(3-phenoxypropionyl)anthranilate；Methyl 2-(3-phenoxypropanoylamino)benzoate
• CAS: 6047-28-5
• 化学式: C₁₇H₁₇NO₄
• mdl: MFCD01181589
• 分子量: 299.326
• InChiKey: IMROBIVZIOAOJT-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：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为产物：
  描述：

  3-苯氧基丙酸 在 五氯化磷 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 methyl N-(3-phenoxypropionoyl)anthranilate
  参考文献：
  名称：

  Synthesis and Caco-2 cell permeability of N-substituted anthranilamide esters as ADP inhibitor in platelets

  摘要：

  我们合成了 12 种 N-取代的蒽酰胺酯（1-5、8、9、12、13 和 15-17），并评估了它们抑制由 5′-二磷酸腺苷（10 μM）诱导的洗过的人血小板体外聚集的能力。在受试化合物中，5-羟基-N-（2-苯氧基丙酰基）蒽酸 dl-正丁酯（9，IC50 = 10.5 μM）的抗血小板活性最强，乙酯 8（IC50 = 11.5-（对甲苯磺酰氧基）-N-（2-苯氧基丙酰基）蒽酸 dl-乙基和 dl-正丁酯（12，IC50 = 13.1 μM和13，IC50 = 14.0 μM）、N-(2-苯氧基丁酰)蒽酸二甲基酯（2，IC50 = 12.7 μM）、dl-N-（2-苯氧基丙酰基）蒽酸（5，IC50 = 13.7 μM）的抗血小板活性低于 8 和 9。5-hydroxy-N-(4′-acetoxybenzoyl)anthranilate 正丁酯（15，IC50 = 28.3 μM）显示出中等活性。化合物 1（IC50 = 42.8 μM）、4（IC50 = 56.7 μM）、16（IC50 = 51.0 μM）和 17（IC50 = 49.8 μM）显示出较低的抗血小板活性。N-苯氧基乙酰基噻喃甲酯（3，IC50 = 78.0 μM）的抗血小板活性最低。支链烷基化合物（2 和 5）的活性高于直链化合物（3 和 4）。通过 Caco-2 细胞渗透性试验测定，化合物 2 和 9 的表观渗透系数（Papp，cm/s）值分别为 45.34 ± 4.67 和 33.17 ± 5.15 × 10-6 cm/s 。

  DOI：

  10.1007/s12272-014-0353-1

文献信息

• Synthesis and Caco-2 cell permeability of N-substituted anthranilamide esters as ADP inhibitor in platelets
  作者：Sohee Kim、Beom Soo Shin、Eunsook Ma

  DOI：10.1007/s12272-014-0353-1

  日期：2015.6

  Twelve N-substituted anthranilamide esters (1–5, 8, 9, 12, 13, and 15–17) were synthesized and evaluated for their ability to inhibit the in vitro aggregation by washed human platelets induced by adenosine 5′-diphosphate (10 μM). The antiplatelet activity of dl-n-butyl 5-hydroxy-N-(2-phenoxypropionyl)anthranilate (9, IC50 = 10.5 μM) was most active among the tested compounds and ethyl ester 8 (IC50 = 11.2 μM) showed the second most activity. dl-Ethyl and dl-n-butyl 5-(p-toluenesulfonyloxy)-N-(2-phenoxypropionyl)anthranilate (12, IC50 = 13.1 μM and 13, IC50 = 14.0 μM), dl-methyl N-(2-phenoxybutyryl)anthranilate (2, IC50 = 12.7 μM), dl-N-(2-phenoxypropionyl)anthranilic acid (5, IC50 = 13.7 μM) displayed lower antiplatelet activity than 8 and 9. Compound 5 was more active than methyl ester prodrug 1. n-Butyl 5-hydroxy-N-(4′-acetoxybenzoyl)anthranilate (15, IC50 = 28.3 μM) showed moderate activity. Compounds 1 (IC50 = 42.8 μM), 4 (IC50 = 56.7 μM), 16 (IC50 = 51.0 μM), and 17 (IC50 = 49.8 μM) exhibited low antiplatelet activity. Methyl N-phenoxyacetylanthranilate (3, IC50 = 78.0 μM) showed the lowest antiplatelet activity. The compounds with branched alkyl chain (2 and 5) were more active than compounds with straight chain (3 and 4). The apparent permeability coefficient (Papp, cm/s) values of compounds 2 and 9 were determined as 45.34 ± 4.67 and 33.17 ± 5.15 × 10−6 cm/s by Caco-2 cell permeability assay.

  我们合成了 12 种 N-取代的蒽酰胺酯（1-5、8、9、12、13 和 15-17），并评估了它们抑制由 5′-二磷酸腺苷（10 μM）诱导的洗过的人血小板体外聚集的能力。在受试化合物中，5-羟基-N-（2-苯氧基丙酰基）蒽酸 dl-正丁酯（9，IC50 = 10.5 μM）的抗血小板活性最强，乙酯 8（IC50 = 11.5-（对甲苯磺酰氧基）-N-（2-苯氧基丙酰基）蒽酸 dl-乙基和 dl-正丁酯（12，IC50 = 13.1 μM和13，IC50 = 14.0 μM）、N-(2-苯氧基丁酰)蒽酸二甲基酯（2，IC50 = 12.7 μM）、dl-N-（2-苯氧基丙酰基）蒽酸（5，IC50 = 13.7 μM）的抗血小板活性低于 8 和 9。5-hydroxy-N-(4′-acetoxybenzoyl)anthranilate 正丁酯（15，IC50 = 28.3 μM）显示出中等活性。化合物 1（IC50 = 42.8 μM）、4（IC50 = 56.7 μM）、16（IC50 = 51.0 μM）和 17（IC50 = 49.8 μM）显示出较低的抗血小板活性。N-苯氧基乙酰基噻喃甲酯（3，IC50 = 78.0 μM）的抗血小板活性最低。支链烷基化合物（2 和 5）的活性高于直链化合物（3 和 4）。通过 Caco-2 细胞渗透性试验测定，化合物 2 和 9 的表观渗透系数（Papp，cm/s）值分别为 45.34 ± 4.67 和 33.17 ± 5.15 × 10-6 cm/s 。
• N-Cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites
  作者：Arundhasa Chandrabalan、Martin J. McPhillie、Alyn H. Morice、Andrew N. Boa、Laura R. Sadofsky

  DOI：10.1016/j.ejmech.2019.02.074

  日期：2019.5

  The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel, which detects noxious stimuli leading to pain, itch and cough. However, the mechanism(s) of channel modulation by many of the known, non-reactive modulators has not been fully elucidated. N-Cinnamoylanthranilic acid derivatives (CADs) contain structural elements from the TRPA1 modulators cinnamaldehyde and flufenamic acid, so it was hypothesized that specific modulators could be found amongst them and more could be learnt about modulation of TRPA1 with these compounds. A series of CADs was therefore screened for agonism and antagonism in HEK293 cells stably transfected with WT-human (h)TRPA1, or C621A, F909A or F944A mutant hTRPA1. Derivatives with electron-withdrawing and/or electron-donating substituents were found to possess different activities. CADs with inductive electron-withdrawing groups were agonists with desensitising effects, and CADs with electron-donating groups were either partial agonists or antagonists. Site-directed mutagenesis revealed that the CADs do not undergo conjugate addition reaction with TRPA1, and that F944 is a key residue involved in the non covalent modulation of TRPA1 by CADs, as well as many other structurally distinct non-reactive TRPA1 ligands already reported. (C) 2019 Elsevier Masson SAS. All rights reserved.