N-methoxy-N-methyl-2-(4-fluorophenoxy)ethanamide | 524713-99-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-methoxy-N-methyl-2-(4-fluorophenoxy)ethanamide
• 英文别名: 2-(4-fluorophenoxy)-N-methoxy-N-methylacetamide
• CAS: 524713-99-3
• 化学式: C₁₀H₁₂FNO₃
• mdl: MFCD19445209
• 分子量: 213.209
• InChiKey: MIIHTIGREDJGEO-UHFFFAOYSA-N

物化性质

• 沸点：
  290.7±46.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methoxy-N-methyl-2-(4-fluorophenoxy)ethanamide 在 B-isopinocampheyl-9-borabicyclo[3.3.1]nonane 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (3R)-4-(4-fluorophenoxy)-3-hydroxy-1-butyne
  参考文献：
  名称：

  Novel 3-Oxa Lipoxin A₄ Analogues with Enhanced Chemical and Metabolic Stability Have Anti-inflammatory Activity in Vivo

  摘要：

  Lipoxin A(4) (LXA(4)) is a structurally and functionally distinct natural product called an eicosanoid, which displays immunomodulatory and anti-inflammatory activity but is rapidly metabolized to inactive catabolites in vivo. A previously described analogue of LXA(4), methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), was shown to have a poor pharmacokinetic profile after both oral and intravenous administration, as well as sensitivity to acid and light. The chemical stability of the corresponding E,E,E-trien-11-yne analogue, 3, was improved over 2 without loss of efficacy in the mouse air pouch model of inflammation. Careful analysis of the plasma samples from the pharmacokinetic assays for both 2 and 3 identified a previously undetected metabolite, which is consistent with metabolism by beta-oxidation. The formation of the oxidative metabolites was eliminated with the corresponding 3-oxatetraene, 4, and the 3-oxatrien-11-yne, 5, analogues of 2. Evaluation of 3-oxa analogues 4 and 5 in calcium ionophore-induced acute skin inflammation model demonstrated similar topical potency and efficacy compared to 2. The 3-oxatrien-11-yne analogue, 5, is equipotent to 2 in an animal model of inflammation but has enhanced metabolic and chemical stability and a greatly improved pharmacokinetic profile.

  DOI：

  10.1021/jm030569l
• 作为产物：
  描述：

  4-氟苯氧乙酸 在 草酰氯 、 potassium carbonate 、 乙酸乙酯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 N-methoxy-N-methyl-2-(4-fluorophenoxy)ethanamide
  参考文献：
  名称：

  Novel 3-Oxa Lipoxin A₄ Analogues with Enhanced Chemical and Metabolic Stability Have Anti-inflammatory Activity in Vivo

  摘要：

  Lipoxin A(4) (LXA(4)) is a structurally and functionally distinct natural product called an eicosanoid, which displays immunomodulatory and anti-inflammatory activity but is rapidly metabolized to inactive catabolites in vivo. A previously described analogue of LXA(4), methyl (5R,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate (2, ATLa), was shown to have a poor pharmacokinetic profile after both oral and intravenous administration, as well as sensitivity to acid and light. The chemical stability of the corresponding E,E,E-trien-11-yne analogue, 3, was improved over 2 without loss of efficacy in the mouse air pouch model of inflammation. Careful analysis of the plasma samples from the pharmacokinetic assays for both 2 and 3 identified a previously undetected metabolite, which is consistent with metabolism by beta-oxidation. The formation of the oxidative metabolites was eliminated with the corresponding 3-oxatetraene, 4, and the 3-oxatrien-11-yne, 5, analogues of 2. Evaluation of 3-oxa analogues 4 and 5 in calcium ionophore-induced acute skin inflammation model demonstrated similar topical potency and efficacy compared to 2. The 3-oxatrien-11-yne analogue, 5, is equipotent to 2 in an animal model of inflammation but has enhanced metabolic and chemical stability and a greatly improved pharmacokinetic profile.

  DOI：

  10.1021/jm030569l

文献信息

• Lipoxin A4 analogs
  申请人：Schering Aktiengesellschaft

  公开号：US20040162433A1

  公开（公告）日：2004-08-19

  This invention is directed to lipoxin A 4 analogs of the following formula (I) and (II): 1 wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein. These analogs are useful in treating inflammatory and autoimmune disorders in humans. These analogs are also useful in treating pulmonary or respiratory tract inflammation in humans.

  本发明涉及以下公式（I）和（II）的脂氧素A4类似物：1其中R1，R2，R3，R4和R5如本文所述。这些类似物在治疗人类的炎症和自身免疫性疾病方面非常有用。这些类似物还在治疗人类的肺部或呼吸道炎症方面非常有用。
• Intermediates for the preparation of lipoxin A4 analogs
  申请人：Grossbach Danja

  公开号：US20070105949A1

  公开（公告）日：2007-05-10

  This invention is directed to compounds useful as intermediates in the synthesis of lipoxin A 4 analogs of the following formulas (I) and (II): wherein R 1 , R 2 , R 3 , R 4 and R 5 are described herein. These analogs are useful in treating inflammatory and autoimmune disorders in humans. These analogs are also useful in treating pulmonary or respiratory tract inflammation in humans.

  本发明涉及化合物，其作为合成脂氧素A4类似物的中间体有用，该类似物的化学式为(I)和(II)，其中R1、R2、R3、R4和R5如本文所述。这些类似物对于治疗人体内的炎症和自身免疫性疾病有用。这些类似物也对于治疗人体内的肺部或呼吸道炎症有用。
• Inhibition of Group IVA Cytosolic Phospholipase A₂ by Thiazolyl Ketones in Vitro, ex Vivo, and in Vivo
  作者：George Kokotos、Astrid J. Feuerherm、Efrosini Barbayianni、Ishita Shah、Mari Sæther、Victoria Magrioti、Thuy Nguyen、Violetta Constantinou-Kokotou、Edward A. Dennis、Berit Johansen

  DOI：10.1021/jm500192s

  日期：2014.9.25

  Group WA cytosolic phospholipase A(2) (GIVA cPLA(2)) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA(2), exhibiting an X-I(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 mu M. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE(2) levels.
• LIPOXIN A4 ANALOGS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1472209A2

  公开（公告）日：2004-11-03
• US6831186B2
  申请人：——

  公开号：US6831186B2

  公开（公告）日：2004-12-14