3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(2-oxo-3-(4-phenoxyphenoxy)-propyl)-1H-indole-5-carboxylic acid | 1138028-76-8

• 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-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(2-oxo-3-(4-phenoxyphenoxy)-propyl)-1H-indole-5-carboxylic acid
• 英文别名: 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-[2-oxo-3-(4-phenoxyphenoxy)propyl]indole-5-carboxylic acid
• CAS: 1138028-76-8
• 化学式: C₂₇H₂₁N₃O₆
• 分子量: 483.48
• InChiKey: FSCCMVGQQAJKOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-[2-oxo-3-(4-phenoxyphenoxypropyl)]indole-5-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以94%的产率得到3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(2-oxo-3-(4-phenoxyphenoxy)-propyl)-1H-indole-5-carboxylic acid
  参考文献：
  名称：

  1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability

  摘要：

  Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position I have been found to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In the course of structure-activity relationship studies, we investigated the effect of a substitution of indole 3 position with acyl, alkyl, and oxadiazole residues. The highest increase of inhibitory potency could be achieved by a 3-methyl-1,2, 4-oxadiazol-5-yl-moiety. Appropriate compound 40 revealed an IC50 of 0.0021 mu M against isolated cPLA(2)alpha. In a cellular assay applying human platelets 40 blocked cPLA(2)alpha. activity even with an IC50 of 0.0006 mu M. Metabolic stability and aqueous solubility of the target compounds were also determined. Furthermore, one selected compound was tested for peroral bioavailability in mice.

  DOI：

  10.1021/jm101094p

文献信息

• USE OF INHIBITORS OF PHOSPHOLIPASE A2 FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTION
  申请人：Twincore Zentrum für Experimentelle und Klinische Infektionsforschung GmbH

  公开号：EP2614144A1

  公开（公告）日：2013-07-17
• [DE] NEUE HETEROARYLSUBSTITUIERTE ACETONDERIVATE, GEEIGNET ZUR HEMMUNG DER PHOSPHOLIPASE A2<br/>[EN] NOVEL HETEROARYL-SUBSTITUTED ACETONE DERIVATIVE, SUITABLE FOR INHIBITING PHOSPHOLIPASE A2<br/>[FR] NOUVEAUX DÉRIVÉS DE L'ACÉTONE SUBSTITUÉS PAR UN HÉTÉROARYLE, APPROPRIÉS COMME INHIBITEURS DE LA PHOSPHOLIPASE A2
  申请人：UNIV MUENSTER WILHELMS

  公开号：WO2009040314A2

  公开（公告）日：2009-04-02

  Die vorliegende Erfindung betrifft neue heteroarylsubstituierte Acetonderivate, die das Enzym Phospholipase A2 hemmen, sowie pharmazeutische Mittel umfassend diese Verbindungen der allgemeinen Formel (I) wie nachstehend angegeben.
• [EN] USE OF INHIBITORS OF PHOSPHOLIPASE A2 FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTION<br/>[FR] UTILISATION D'INHIBITEURS DE PHOSPHOLIPASE A2 POUR TRAITER OU PRÉVENIR UNE INFECTION À FLAVIVIRUS
  申请人：TWINCORE ZENTRUM FUER EXPERIMENTELLE UND KLINISCHE INFEKTIONSFORSCHUNG GMBH

  公开号：WO2012031763A1

  公开（公告）日：2012-03-15

  The invention relates to Phospholipase A2 (hereinafter also referred to as PLA2) inhibitors for use in the treatment or prevention of flavivirus infection, in particular an infection with a flavivirus of the genus Flavi or the genus Hepaci. The invention also provides a pharmaceutical formulation for use in the treatment or prevention of an infection with a flavivirus of the genus Flavi or the genus Hepaci and a method of preventing or treating an infection with a flavivirus of the genus Flavi or the genus Hepaci.
• 1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability
  作者：Stefanie Bovens、Alwine Schulze Elfringhoff、Martina Kaptur、Dirk Reinhardt、Michael Schäfers、Matthias Lehr

  DOI：10.1021/jm101094p

  日期：2010.12.9

  Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position I have been found to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In the course of structure-activity relationship studies, we investigated the effect of a substitution of indole 3 position with acyl, alkyl, and oxadiazole residues. The highest increase of inhibitory potency could be achieved by a 3-methyl-1,2, 4-oxadiazol-5-yl-moiety. Appropriate compound 40 revealed an IC50 of 0.0021 mu M against isolated cPLA(2)alpha. In a cellular assay applying human platelets 40 blocked cPLA(2)alpha. activity even with an IC50 of 0.0006 mu M. Metabolic stability and aqueous solubility of the target compounds were also determined. Furthermore, one selected compound was tested for peroral bioavailability in mice.