arachidonic acid hydroperoxide | 21290-17-5

• 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: arachidonic acid hydroperoxide
• 英文别名: hydrogen peroxyarachidonate；arachidonic hydroperoxide；Peroxyarachidonsaeure；arachidonate oxygen；(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraeneperoxoic acid
• CAS: 21290-17-5
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: DMIZOMNOESDTFZ-DOFZRALJSA-N

物化性质

• 沸点：
  439.7±55.0 °C(Predicted)
• 密度：
  0.959±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  arachidonic acid hydroperoxide 在 lead(IV) acetate 、 正丁基锂 、 高氯酸 、 sodium sulfate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 6.25h， 生成 (5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid methyl ester
  参考文献：
  名称：

  Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain

  摘要：

  To examine the effect of changing the length and branching of the end pentyl chain (C5H11) of anandamide (AN), various analogs 1a-h and 2a-f were synthesized from either the known aldehyde ester 6a or from the alcohol 6b and tested for their pharmacological activity. A reproducible procedure was developed for the conversion of arachidonic acid to 6a or 6b in gram quantities (overall yield 15%). The appropriate tetraene esters 7 were prepared by carrying out a Wittig reaction, between 6a and the ylide generated from the phosphonium salt of the appropriate alkyl halide or between the ylide of 6d (prepared from 6a --> 6b --> 6c --> 6d) and the appropriate alkyl aldehydes. They were then hydrolyzed to the corresponding acids and transformed into AN analogs 1 via their acid chlorides then treated with excess ethanolamine. alpha-Alkylation of esters 7 gave compounds 8 which were hydrolyzed to the corresponding acids. These acids via their acid chlorides and subsequent treatment with excess fluoroethylamine gave the target compounds 2. In this way analogs 1e and 2a-c were synthesized from 6d while all the remaining analogs were prepared from 6a. In order to assess the optimal length of the alkyl terminus, analogs 1a-d were prepared and showed moderately high affinities (18-55 nM). However analogs 1a-c failed to produce significant pharmacological effects at doses up to 30 mg/kg. Analog 1d was found to be a weak partial agonist. The reason for the lack of activity in 1a-c is presently not clear. Like the THCs, the branching of the end pentyl chain in AN (1e-h) increased potency both in in vitro and in vivo activities; the dimethylheptyl (DMH) analog 1e was the most potent in the series. Similar alkyl substitutions were carried out in the fluoro-2-methylanandamide series (2a-f), and all of these analogs had high receptor affinities (1-14 nM), the DMH analog 2a being the most potent. With a few exceptions they showed robust pharmacological effects, and AN-like profiles, It was shown that the SAR of the end pentyl chain in AN is very similar to that of THCs. However, the magnitude of enhanced potency observed when the side chain of THC was changed from straight to branched was not observed when the end chain of AN was similarly changed.

  DOI：

  10.1021/jm970212f
• 作为产物：
  描述：

  花生四烯酸 在 lithium hydroxide 、 正丁基锂 、 双氧水 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 arachidonic acid hydroperoxide
  参考文献：
  名称：

  放射性光亲和性花生四烯酸类似物的合成

  摘要：

  通过偶联20-羟基花生四烯酸和2-叠氮基-5-碘苯甲酸合成了一种基于花生四烯酸的新型光亲和探针。使用一种新的温和安全的方法获得了形成20-羟基花生四烯酸所需的关键环氧化物。

  DOI：

  10.1016/s0040-4039(00)76742-6

文献信息

• UVA irradiation of fatty acids and their oxidized products substantially increases their ability to generate singlet oxygen
  作者：Johannes Regensburger、Tim Maisch、Alena Knak、Anita Gollmer、Ariane Felgentraeger、Karin Lehner、Wolfgang Baeumler

  DOI：10.1039/c3cp51399h

  日期：——

  UVA radiation plays an important role for adverse reactions in human tissue. UVA penetrates epidermis and dermis of skin being absorbed by various biomolecules, especially endogenous photosensitizers. This may generate deleterious singlet oxygen (1O2) that oxidizes fatty acids in cell membranes, lipoproteins, and other lipid-containing structures such as the epidermal barrier. Indications exist that fatty acids are not only the target of 1O2 but also act as potential photosensitizers under UVA irradiation, if already oxidized. Five different fatty acids in ethanol solution (stearic, oleic, linoleic, linolenic and arachidonic acid) were exposed to UVA radiation (355 nm, 100 mW) for 30 seconds. 1O2 luminescence was detected time-resolved at 1270 nm and confirmed in spectrally-resolved experiments. The more double bonds fatty acids have the more 1O2 photons were detected. In addition, fatty acids were continuously exposed to broadband UVA for up to 240 min. During that time span, UVA absorption and 1O2 luminescence substantially increased with irradiation time, reached a maximum and decreased again. HPLC-MS analysis showed that the amount of peroxidized fatty acids and the 1O2 generation increased and decreased in parallel. This indicates the high potential of peroxidized fatty acids to produce 1O2 under UVA irradiation. In conclusion, fatty acids along with peroxidized products are weak endogenous photosensitizers but become strong photosensitizers under continuous UVA irradiation. Since fatty acids and their oxidized products are ubiquitous in living cells and in skin, which is frequently and long-lasting exposed to UVA radiation, this photosensitizing effect may contribute to initiation of deleterious photooxidative processes in tissue.

  UVA辐射在人类组织的不良反应中发挥着重要作用。UVA能够穿透皮肤的表皮和真皮，被各种生物分子吸收，特别是内源性光敏剂。这可能会产生有害的单重态氧（1O2），其会氧化细胞膜、脂蛋白和其他含脂结构（如表皮屏障）中的脂肪酸。有迹象表明，脂肪酸不仅是1O2的靶点，而且在已被氧化的情况下，还可以在UVA照射下充当潜在的光敏剂。在乙醇溶液中，五种不同的脂肪酸（硬脂酸、油酸、亚油酸、亚麻酸和花生酸）暴露于UVA辐射（355 nm，100 mW）下30秒。采用时间分辨法在1270 nm处检测到1O2的发光，并在光谱分辨实验中得到了确认。脂肪酸的双键数量越多，检测到的1O2光子就越多。此外，脂肪酸还在宽谱UVA下持续暴露长达240分钟。在此时间段内，UVA的吸收和1O2发光随着照射时间的增加显著上升，达到最大值后又下降。HPLC-MS分析显示，过氧化脂肪酸的量和1O2的生成在增加和减少的过程中是并行的。这表明过氧化脂肪酸在UVA照射下产生1O2的潜力很高。总之，脂肪酸及其过氧化产物作为弱的内源性光敏剂，但在持续的UVA照射下会成为强光敏剂。由于脂肪酸及其氧化产物在活细胞和皮肤中普遍存在，而皮肤往往会长时间暴露于UVA辐射中，这种光敏化效应可能会促成组织中有害光氧化过程的启动。
• Compounds and methods for the inhibition of the expression of VCAM-1
  申请人：——

  公开号：US20020188118A1

  公开（公告）日：2002-12-12

  This invention is in the area of methods and compositions for the inhibition of the expression of VCAM-1 and, in particular, for the treatment of diseases mediated by VCAM-1, including cardiovascular and inflammatory diseases.

  本发明涉及用于抑制VCAM-1表达的方法和组合物，特别是用于治疗由VCAM-1介导的疾病，包括心血管和炎症性疾病。
• 1,3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders
  申请人：Atherogenics Pharmaceuticals, Inc.

  公开号：US20030236298A1

  公开（公告）日：2003-12-25

  It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease.

  已经发现了某些1,3-双-(取代苯基)-2-丙烯-1-酮，包括公式(I)化合物抑制VCAM-1的表达，因此可用于治疗受VCAM-1介导的疾病的患者。VCAM-1介导的炎症性疾病的例子包括但不限于关节炎、哮喘、皮炎、囊性纤维化、移植后晚期和慢性实体器官排斥、多发性硬化症、系统性红斑狼疮、炎症性肠病、自身免疫性糖尿病、糖尿病视网膜病变、鼻炎、缺血再灌注损伤、血管成形术后再狭窄、慢性阻塞性肺疾病（COPD）、肾小球肾炎、格雷夫斯病、胃肠道过敏、结膜炎、动脉粥样硬化、冠状动脉疾病、心绞痛和小动脉疾病。
• Chalcone derivatives and their use to treat diseases
  申请人：Ni Liming

  公开号：US20060189549A1

  公开（公告）日：2006-08-24

  The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.

  本发明涉及一般式化合物、药物组合物及使用该一般式化合物或其药学上可接受的盐或酯的方法，其中取代基在申请中定义。
• Sulfonamide-substituted chalcone derivatives and their use to treat diseases
  申请人：Worsencroft J. Kimberly

  公开号：US20050049236A1

  公开（公告）日：2005-03-03

  The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.

  该发明涉及一般式的化合物、药物组成物和使用该化合物的方法，或其药学上可接受的盐或酯，其中取代基在申请中有定义。