2-{1-[(4-chlorophenyl)carbonyl]-5-hydroxy-2-methylindol-3-yl}-N-(3-hydroxypropyl)acetamide

• 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: 2-{1-[(4-chlorophenyl)carbonyl]-5-hydroxy-2-methylindol-3-yl}-N-(3-hydroxypropyl)acetamide
• 英文别名: 2-[1-(4-chlorobenzoyl)-5-hydroxy-2-methylindol-3-yl]-N-(3-hydroxypropyl)acetamide
• 化学式: C₂₁H₂₁ClN₂O₄
• 分子量: 400.862
• InChiKey: ROGIZQKZYSAYNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  91.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-[1-(4-氯苯甲酰基)-5-羟基-2-甲基吲哚-3-基]乙酸 、 3-氨基-1-丙醇 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以57%的产率得到2-{1-[(4-chlorophenyl)carbonyl]-5-hydroxy-2-methylindol-3-yl}-N-(3-hydroxypropyl)acetamide
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Indomethacin Derivatives as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors

  摘要：

  Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.

  DOI：

  10.1021/jm0611861

文献信息

• WO2006/99416
  申请人：——

  公开号：——

  公开（公告）日：——
• Structure-Based Design, Synthesis, and Biological Evaluation of Indomethacin Derivatives as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors
  作者：Shiow-Jyi Wey、Michael E. Augustyniak、Edward D. Cochran、James L. Ellis、Xinqin Fang、David S. Garvey、David R. Janero、L. Gordon Letts、Allison M. Martino、Terry L. Melim、Madhavi G. Murty、Steward K. Richardson、Joseph D. Schroeder、William M. Selig、A. Mark Trocha、Roseanne S. Wexler、Delano V. Young、Irina S. Zemtseva、Brian M. Zifcak

  DOI：10.1021/jm0611861

  日期：2007.12.13

  Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.