((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-((1-naphthalenyl)methyl)-1H-indol-4-yl)oxy)acetic acid methyl ester | 172733-05-0

• 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: ((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-((1-naphthalenyl)methyl)-1H-indol-4-yl)oxy)acetic acid methyl ester
• 英文别名: Methyl 2-[2-methyl-1-(naphthalen-1-ylmethyl)-3-oxamoylindol-4-yl]oxyacetate
• CAS: 172733-05-0
• 化学式: C₂₅H₂₂N₂O₅
• 分子量: 430.46
• InChiKey: UUHZUERYXHKMHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-((1-naphthalenyl)methyl)-1H-indol-4-yl)oxy)acetic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以75%的产率得到[[3-(2-amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid
  参考文献：
  名称：

  Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 3. Indole-3-glyoxamides

  摘要：

  The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA(2). We describe here the extension of the structure-activity relationship to include a series of indole-3-glyoxamide derivatives. Functionalized indole-3-glyoxamides with an acidic substituent appended to the 4- or 5-position of the indole ring were prepared and tested as inhibitors of hnps-PLA(2). It was found that the indole-3-glyoxamides with a 4-oxyacetic acid substituent had optimal inhibitory activity. These inhibitors exhibited an improvement in potency over the best of the indole-3-acetamides, and LY315920 (6m) was selected for evaluation clinically as an hnps-PLA(2) inhibitor.

  DOI：

  10.1021/jm960487f
• 作为产物：
  描述：

  4-甲氧基-2-甲基-1H-吲哚 在 氨 、 三溴化硼 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 24.08h， 生成 ((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-((1-naphthalenyl)methyl)-1H-indol-4-yl)oxy)acetic acid methyl ester
  参考文献：
  名称：

  Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A₂. 3. Indole-3-glyoxamides

  摘要：

  The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA(2). We describe here the extension of the structure-activity relationship to include a series of indole-3-glyoxamide derivatives. Functionalized indole-3-glyoxamides with an acidic substituent appended to the 4- or 5-position of the indole ring were prepared and tested as inhibitors of hnps-PLA(2). It was found that the indole-3-glyoxamides with a 4-oxyacetic acid substituent had optimal inhibitory activity. These inhibitors exhibited an improvement in potency over the best of the indole-3-acetamides, and LY315920 (6m) was selected for evaluation clinically as an hnps-PLA(2) inhibitor.

  DOI：

  10.1021/jm960487f

文献信息

• [EN] ADIPOSITY-MODULATING MOLECULES AND USES THEREFOR<br/>[FR] MOLÉCULES MODULANT L'ADIPOSITÉ ET UTILISATIONS ASSOCIÉES
  申请人：UNIV QUEENSLAND

  公开号：WO2013067579A1

  公开（公告）日：2013-05-16

  Disclosed are methods and compositions for modulating adiposity-related conditions, which utilize inhibitors of phospholipase A2, and more particularly phospholipase A2 Group IIa (PLA2G2A). Representative adiposity-related conditions include obesity, type II diabetes, adipose inflammation, metabolic dysfunction, cardiovascular diseases and more generally, metabolic syndrome.

  揭示了一种调节与脂肪相关疾病的方法和组合物，利用磷脂酶A2的抑制剂，尤其是磷脂酶A2第IIa组（PLA2G2A）。代表性的与脂肪相关疾病包括肥胖、2型糖尿病、脂肪炎症、代谢功能障碍、心血管疾病以及更一般的代谢综合征。
• TREATMENT OF CARDIOVASCULAR DISEASE AND DYSLIPIDEMIA USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS AND SPLA2 INHIBITOR COMBINATION THERAPIES
  申请人：Anthera Pharmaceuticals, Inc.

  公开号：EP2154958A1

  公开（公告）日：2010-02-24
• TRAITEMENT D'ÉVÉNEMENTS CARDIAQUES MAJEURS INDÉSIRABLES ET DU SYNDROME CORONAIRE AIGU À L'AIDE DE TRAITEMENTS THÉRAPEUTIQUES UTILISANT UN INHIBITEUR DE LA PHOSPHOLIPASE SÉCRÉTÉE A2 (SPLA2) OU DE COMBINAISONS THÉRAPEUTIQUES AVEC UN INHIBITEUR DE SPLA2
  申请人：Anthera Pharmaceuticals, Inc.

  公开号：EP2393358A1

  公开（公告）日：2011-12-14
• SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITOR AND NIACIN DRUG COMPOSITIONS AND METHODS FOR TREATING CARDIOVASCULAR DISEASE AND DYSLIPIDEMIA
  申请人：Anthera Pharmaceuticals, Inc.

  公开号：EP2395837A1

  公开（公告）日：2011-12-21
• USE OF SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS TO DECREASE SPLA2 LEVELS
  申请人：Trias Joaquim

  公开号：US20090062369A1

  公开（公告）日：2009-03-05

  Administration of sPLA 2 inhibitors has been found to decrease sPLA 2 levels in human serum. Provided herein are methods of decreasing serum sPLA 2 levels in a subject in need thereof, as well as methods for accurately measuring sPLA 2 levels in a serum sample.