Pentanoic acid 2-(5-methoxy-2-methyl-1H-indol-3-yl)-ethyl ester | 328395-11-5

• 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: Pentanoic acid 2-(5-methoxy-2-methyl-1H-indol-3-yl)-ethyl ester
• 英文别名: 2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl pentanoate
• CAS: 328395-11-5
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: KTKVLQDPHMDXMS-UHFFFAOYSA-N

物化性质

• 沸点：
  445.2±40.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Pentanoic acid 2-(5-methoxy-2-methyl-1H-indol-3-yl)-ethyl ester 、 4-氯苯甲酰氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以34%的产率得到Pentanoic acid 2-[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-ethyl ester
  参考文献：
  名称：

  Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors

  摘要：

  Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.073
• 作为产物：
  描述：

  5-甲氧基-2-甲基-3-吲哚乙酸甲酯 在 4-二甲氨基吡啶 、 锂硼氢 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 Pentanoic acid 2-(5-methoxy-2-methyl-1H-indol-3-yl)-ethyl ester
  参考文献：
  名称：

  Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors

  摘要：

  Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.073

文献信息

• Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors
  作者：Amit S. Kalgutkar、Brenda C. Crews、Sam Saleh、Daniel Prudhomme、Lawrence J. Marnett

  DOI：10.1016/j.bmc.2005.07.073

  日期：2005.12

  Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs. (c) 2005 Elsevier Ltd. All rights reserved.