[1-(2-chloropyridine-4-carbonyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester | 1254180-95-4

• 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: [1-(2-chloropyridine-4-carbonyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester
• CAS: 1254180-95-4
• 化学式: C₂₅H₂₁ClN₂O₄
• 分子量: 448.906
• InChiKey: ZACAEMAMGVWAFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.98
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  70.42
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-氟磺酰基二氟乙酸 、 [1-(2-chloropyridine-4-carbonyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester 以 乙腈 为溶剂， 反应 40.0h， 以32%的产率得到[1-(N-difluoromethyl-1,2-dihydropyrid-2-one-4-carbonyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of indomethacin analogs possessing a N-difluoromethyl-1,2-dihydropyrid-2-one ring system: A search for novel cyclooxygenase and lipoxygenase inhibitors

  摘要：

  A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a C=O (14a-b) or CH2 (19a-b) linker to the indole N-1-position. In this regard, replacement of the 4-chlorobenzoyl group present in indomethacin by N-difluoromethyl-1,2-dihydropyrid-2-one-4-(or 5-)carbonyl and N-difluoromethyl-1,2-dihydropyrid-2-one-4-yl(or 5-yl)methylene moieties furnished compounds showing no inhibitory activities against the COX-2/5-LOX enzymes (except for the weak but selective COX-2 inhibitor 19a, COX-2 IC50 = 31 mu M), and moderate in vivo anti-inflammatory activities (except for the methylene compound 19a that was inactive). These structure-activity data indicate replacement of the 4-chlorobenzoyl group present in indomethacin by a N-difluoromethyl-1,2-dihydropyrid-2-one ring system connected by a C=O or CH2 linker is not a suitable approach for the design of dual COX-2/5-LOX inhibitory analogs of indomethacin. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.132
• 作为产物：
  描述：

  2-氯吡啶-4-甲酰氯 、 苄基5-甲氧基-2-甲基吲哚-3-乙酸酯 在 4-dimethylaminopyridine 、 2-amino-3,3-dimethylbutane 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 以95%的产率得到[1-(2-chloropyridine-4-carbonyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid benzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of indomethacin analogs possessing a N-difluoromethyl-1,2-dihydropyrid-2-one ring system: A search for novel cyclooxygenase and lipoxygenase inhibitors

  摘要：

  A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a C=O (14a-b) or CH2 (19a-b) linker to the indole N-1-position. In this regard, replacement of the 4-chlorobenzoyl group present in indomethacin by N-difluoromethyl-1,2-dihydropyrid-2-one-4-(or 5-)carbonyl and N-difluoromethyl-1,2-dihydropyrid-2-one-4-yl(or 5-yl)methylene moieties furnished compounds showing no inhibitory activities against the COX-2/5-LOX enzymes (except for the weak but selective COX-2 inhibitor 19a, COX-2 IC50 = 31 mu M), and moderate in vivo anti-inflammatory activities (except for the methylene compound 19a that was inactive). These structure-activity data indicate replacement of the 4-chlorobenzoyl group present in indomethacin by a N-difluoromethyl-1,2-dihydropyrid-2-one ring system connected by a C=O or CH2 linker is not a suitable approach for the design of dual COX-2/5-LOX inhibitory analogs of indomethacin. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.132