(2S)-3-(1H-indol-3-yl)-2-{2-oxo-2-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]acetylamino}propionic acid methyl ester | 1571842-06-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-3-(1H-indol-3-yl)-2-{2-oxo-2-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]acetylamino}propionic acid methyl ester
• 英文别名: 3-(1H-indol-3-yl)-2-{2-oxo-2-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]acetylamino}propionic acid methyl ester
• CAS: 1571842-06-2
• 化学式: C₂₉H₂₅N₃O₆S
• 分子量: 543.6
• InChiKey: VGSKHFCMGREMKD-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  127.33
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2S)-3-(1H-indol-3-yl)-2-{2-oxo-2-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]acetylamino}propionic acid methyl ester 在 水 、 氯甲酸乙酯 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 methyl 2-[[(2S)-3-(1H-indol-3-yl)-2-[[2-[1-(4-methylphenyl)sulfonylindol-3-yl]-2-oxoacetyl]amino]propanoyl]amino]acetate
  参考文献：
  名称：

  Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: Dual inhibition of 5-LOX and COX-2 enzymes

  摘要：

  The indoles bearing a tosyl group at N-1 and a dipeptide substituent at C-3 were screened for anti-inflammatory and anti-hyperalgesic activities. Some of the compounds made significant reduction in the dextran induced swelling and capsaicin induced pain in the albino mice. About 95% reversal in capsaicin induced pain occurred in the presence of 5 mg kg(-1) of compound 7b, 7d and 7h while diclofenac showed 90% reversal when its 10 mg kg(-1) dose was used. In order to examine the mode of action of these compounds; COX-1, COX-2 and 5-LOX enzyme immunoassays were performed. The IC50 of compound 7b for COX-2 and 5-LOX were in the nM range: 5-LOX, IC50 = 2.0 nM; COX-2, IC50 = 6.3 nM, selectivity for COX-2 over COX-1 was 351. The interactions of the compounds with COX-2 and 5-LOX were supported by the physical parameters including K-i, K-a and Delta G. The most potent compounds 7b, 7d and 7h showed no toxicity to the animals and were identified as the promising leads for anti-inflammatory drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.044
• 作为产物：
  描述：

  吲哚-3-乙醛酰氯 在 sodium hydride 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 (2S)-3-(1H-indol-3-yl)-2-{2-oxo-2-[1-(toluene-4-sulfonyl)-1H-indol-3-yl]acetylamino}propionic acid methyl ester
  参考文献：
  名称：

  Lead modification: Amino acid appended indoles as highly effective 5-LOX inhibitors

  摘要：

  N-1 tosyl indoles carrying amino acid as a part of C-3 substituent are identified with considerable 5-LOX inhibitory activities. On the basis of enzyme inhibitory activities and log P, it is found that these compounds are more suitable to use as ester prodrugs. In addition to the significant K-a and K-i for 5-LOX, advantageously the compounds under present investigation do not affect the viability of the cell. The experimental results were also supported by molecular docking of compounds in the active site of 5-LOX. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.027