methyl 2-(1-(4-(1-(7-(hydroxyamino)-7-oxoheptyl)-1H-1,2,3-triazol-4-yl)benzyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate

• 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: methyl 2-(1-(4-(1-(7-(hydroxyamino)-7-oxoheptyl)-1H-1,2,3-triazol-4-yl)benzyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate
• 英文别名: Methyl 2-[1-[[4-[1-[7-(hydroxyamino)-7-oxoheptyl]triazol-4-yl]phenyl]methyl]-5-methoxy-2-methylindol-3-yl]acetate；methyl 2-[1-[[4-[1-[7-(hydroxyamino)-7-oxoheptyl]triazol-4-yl]phenyl]methyl]-5-methoxy-2-methylindol-3-yl]acetate
• 化学式: C₂₉H₃₅N₅O₅
• 分子量: 533.627
• InChiKey: QOLVKRURYSCNMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  吲哚美辛 在 三甲基氯硅烷 、 三异丙基硅烷醇 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 2.83h， 生成 methyl 2-(1-(4-(1-(7-(hydroxyamino)-7-oxoheptyl)-1H-1,2,3-triazol-4-yl)benzyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate
  参考文献：
  名称：

  Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

  摘要：

  We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound lib outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.12.032

文献信息

• Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase
  作者：Idris Raji、Fatima Yadudu、Emily Janeira、Shaghayegh Fathi、Lindsey Szymczak、James Richard Kornacki、Kensei Komatsu、Jian-Dong Li、Milan Mrksich、Adegboyega K. Oyelere

  DOI：10.1016/j.bmc.2016.12.032

  日期：2017.2

  We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound lib outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development. (C) 2016 Elsevier Ltd. All rights reserved.