tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-oxiranylmethylindole-5-carboxylate | 1138028-98-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-oxiranylmethylindole-5-carboxylate
• 英文别名: Tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(oxiran-2-ylmethyl)indole-5-carboxylate
• CAS: 1138028-98-4
• 化学式: C₁₉H₂₁N₃O₄
• 分子量: 355.393
• InChiKey: QCRRGGGBWZFBMU-UHFFFAOYSA-N

物化性质

• 熔点：
  138-139 °C
• 沸点：
  539.8±58.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-苯氧基苯酚 、 tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-oxiranylmethylindole-5-carboxylate 在 4-二甲氨基吡啶 作用下， 反应 1.0h， 以38%的产率得到tert-butyl 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]-3-(3-methyl-1,2,4-oxadiazol-5-yl)-indole-5-carboxylate
  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
• 作为产物：
  描述：

  tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)indole-5-carboxylate 、 环氧氯丙烷 在 四丁基溴化铵 、 potassium hydroxide 作用下， 反应 2.0h， 以86%的产率得到tert-butyl 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-oxiranylmethylindole-5-carboxylate
  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

• NOVEL HETEROARYL-SUBSTITUTED ACETONE DERIVATIVE, SUITABLE FOR INHIBITING PHOSPHOLIPASE A2
  申请人：Lehr Matthias

  公开号：US20100240718A1

  公开（公告）日：2010-09-23

  The present invention relates to novel heteroaryl-substituted acetone derivatives inhibiting the enzyme phospholipase A2, and pharmaceutical agents comprising said compounds.

  本发明涉及一种新型的杂环取代丙酮衍生物，其抑制酶磷脂酶A2，以及包含该化合物的药物制剂。
• NEUE HETEROARYLSUBSTITUIERTE ACETONDERIVATE, GEEIGNET ZUR HEMMUNG DER PHOSPHOLIPASE A2
  申请人：Westfälische Wilhelms-Universität Münster

  公开号：EP2215059A2

  公开（公告）日：2010-08-11
• [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.
• 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.