| 1191428-31-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 1191428-31-5
• 化学式: C₁₀H₁₉NO₅
• 分子量: 233.265
• InChiKey: OVAXHWHXOMLLAQ-DQUBFYRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.88
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  110.02
• 氢给体数：
  5.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  异丙胺 、 1,5-quinide 在 溶剂黄146 作用下， 反应 0.5h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents

  摘要：

  Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappa B was assessed using A549 (Type 11 alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappa B response element. A549-NF-kappa B cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappa B. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappa B inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 mu M. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappa B, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.096

文献信息

• Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents
  作者：Kui Zeng、Karin Emmons Thompson、Charles R. Yates、Duane D. Miller

  DOI：10.1016/j.bmcl.2009.07.096

  日期：2009.9

  Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappa B was assessed using A549 (Type 11 alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappa B response element. A549-NF-kappa B cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappa B. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappa B inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 mu M. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappa B, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going. (C) 2009 Elsevier Ltd. All rights reserved.