2-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 2-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)acetic acid
• 英文别名: 2-(4,5-dihydroxy-10-oxo-9H-anthracen-9-yl)acetic acid
• 化学式: C₁₆H₁₂O₅
• 分子量: 284.268
• InChiKey: CNHMOCZGGOLHRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)acetic acid 在 三乙基硅烷 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 N-(4-aminobutyl)-N-(3-aminopropyl)-2-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)acetamide bistrifluoroacetate
  参考文献：
  名称：

  Synthesis and biological evaluation of new C-10 substituted dithranol pleiotropic hybrids

  摘要：

  Selective alkylation of the antipsoriatic drug dithranol (DTR) at C-10 with tert-butyl bromoacetate, followed by acid-mediated deprotection, produced the corresponding carboxylic acid 4 which was coupled with selectively protected polyamines (PAs), such as putrescine (PUT), spermidine (SPD) and spermine (SPM), dopamine and aliphatic amines and substituted benzylamines producing a series of DTR-PA hybrids, after acid-mediated deprotection, as well as simple amides. The compounds were tested as antioxidants and inhibitors of lipoxygenase (LOX). The amides 4,4'-dimethoxybenzhydrylamide 13 (86% and 95%), 2,4-dimethoxybenzylamide 12 (87% and 81%) and dodecylamide 9 (98% and 74%), and the hybrid DTR-SPM (7) (93% and 87%), showed the highest antioxidant activity in the DPPH and AAPH assays, whereas the most potent inhibitors of LOX were amide 13 (IC50 = 7 mu M), the benzylamide 10 (IC50 = 7.9 mu M) and the butylamide 8 (IC50 = 10 mu M). Molecular binding studies showed that binding of these derivatives into the hydrophobic domain blocks approach of substrate to the active site, inhibiting soybean LOX. Amide 13 presented the highest anti-inflammatory activity (79.7%). The DTR moiety was absolutely necessary for securing high anti-inflammatory potency. Ethyl ester 3 (IC50 = 0.357 mu M) and the amides 9 (IC50 = 0.022 mu M) and 13 (IC50 = 0.56 mu M) exhibited higher antiproliferative activity than DTR (IC50 = 0.945 mu M) on HaCaT keratinocytes whereas amide 13 generally presented better cytocompatibility. Amide 13 is a very promising lead compound for further development as an anti-inflammatory and antiproliferative agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.022
• 作为产物：
  描述：

  地蒽酚 在 三乙基硅烷 、 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 2-(4,5-dihydroxy-10-oxo-9,10-dihydroanthracen-9-yl)acetic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of new C-10 substituted dithranol pleiotropic hybrids

  摘要：

  Selective alkylation of the antipsoriatic drug dithranol (DTR) at C-10 with tert-butyl bromoacetate, followed by acid-mediated deprotection, produced the corresponding carboxylic acid 4 which was coupled with selectively protected polyamines (PAs), such as putrescine (PUT), spermidine (SPD) and spermine (SPM), dopamine and aliphatic amines and substituted benzylamines producing a series of DTR-PA hybrids, after acid-mediated deprotection, as well as simple amides. The compounds were tested as antioxidants and inhibitors of lipoxygenase (LOX). The amides 4,4'-dimethoxybenzhydrylamide 13 (86% and 95%), 2,4-dimethoxybenzylamide 12 (87% and 81%) and dodecylamide 9 (98% and 74%), and the hybrid DTR-SPM (7) (93% and 87%), showed the highest antioxidant activity in the DPPH and AAPH assays, whereas the most potent inhibitors of LOX were amide 13 (IC50 = 7 mu M), the benzylamide 10 (IC50 = 7.9 mu M) and the butylamide 8 (IC50 = 10 mu M). Molecular binding studies showed that binding of these derivatives into the hydrophobic domain blocks approach of substrate to the active site, inhibiting soybean LOX. Amide 13 presented the highest anti-inflammatory activity (79.7%). The DTR moiety was absolutely necessary for securing high anti-inflammatory potency. Ethyl ester 3 (IC50 = 0.357 mu M) and the amides 9 (IC50 = 0.022 mu M) and 13 (IC50 = 0.56 mu M) exhibited higher antiproliferative activity than DTR (IC50 = 0.945 mu M) on HaCaT keratinocytes whereas amide 13 generally presented better cytocompatibility. Amide 13 is a very promising lead compound for further development as an anti-inflammatory and antiproliferative agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.022