(1E,4E)-1,5-bis(3-fluoro-4-hydroxy-5-methoxyphenyl)penta-1,4-dien-3-one | 1616504-31-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (1E,4E)-1,5-bis(3-fluoro-4-hydroxy-5-methoxyphenyl)penta-1,4-dien-3-one
• CAS: 1616504-31-4
• 化学式: C₁₉H₁₆F₂O₅
• 分子量: 362.33
• InChiKey: FBNPNEIMXKOBBP-GGWOSOGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氟-4-羟基-5-甲氧基苯甲醛 、 丙酮 在 盐酸 作用下， 以 乙醇 为溶剂， 以65%的产率得到(1E,4E)-1,5-bis(3-fluoro-4-hydroxy-5-methoxyphenyl)penta-1,4-dien-3-one
  参考文献：
  名称：

  SAR Studies on Curcumin’s Pro-inflammatory Targets: Discovery of Prenylated Pyrazolocurcuminoids as Potent and Selective Novel Inhibitors of 5-Lipoxygenase

  摘要：

  The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (ie., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kappa B, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.

  DOI：

  10.1021/jm500308c

文献信息

• Lipophilic Curcumin Analogs And Methods Of Inhibiting HIV-1, Treating Latent HIV In The Brain, And Preventing HIV-Mediated Cognitive Decline And HIV Dementia
  申请人：Howard University

  公开号：US20160009623A1

  公开（公告）日：2016-01-14

  Compounds having formulas (I) to (VIII), salts thereof, or combinations thereof and pharmaceutical compositions comprising one or more these compounds are described herein for the treatment of HIV and neurodegenerative effects caused by HIV. Also provided herein are methods and a kit for inhibiting HIV-1, treating latent HIV in the brain, and preventing HIV-mediated cognitive decline and HIV dementia comprising administering the compounds having the formulas (I) to (VIII) and pharmaceutical compositions comprising the compounds having these formulas. The compounds having formulas I through VIII are curcumin analogs which are advantageously characterized as having anti-retroviral, neuroprotective, anti-glucosidase, and anti-HIV integrase properties. In one aspect, the pharmaceutical composition is delivered intranasally.

  本文描述了化学式（I）至（VIII）的化合物，其盐或其组合物以及包含这些化合物的制药组合物，用于治疗HIV和由HIV引起的神经退行性效应。本文还提供了用于抑制HIV-1、治疗脑中潜在HIV以及预防HIV介导的认知衰退和HIV痴呆的方法和工具包，包括给予具有化学式（I）至（VIII）的化合物和包含这些化合物的制药组合物。化学式I至VIII的化合物是姜黄素类似物，其具有抗逆转录病毒、神经保护、抗葡萄糖苷酶和抗HIV整合酶特性。在一个方面，制药组合物通过鼻内途径给予。
• Lipophilic curcumin analogs and methods of inhibiting HIV-1, treating latent HIV in the brain, and preventing HIV-mediated cognitive decline and HIV dementia
  申请人：Howard University

  公开号：US11319273B2

  公开（公告）日：2022-05-03

  Compounds having formulas (I) to (VIII), salts thereof, or combinations thereof and pharmaceutical compositions comprising one or more these compounds are described herein for the treatment of HIV and neurodegenerative effects caused by HIV. Also provided herein are methods and a kit for inhibiting HIV-1, treating latent HIV in the brain, and preventing HIV-mediated cognitive decline and HIV dementia comprising administering the compounds having the formulas (I) to (VIII) and pharmaceutical compositions comprising the compounds having these formulas. The compounds having formulas I through VIII are curcumin analogs which are advantageously characterized as having anti-retroviral, neuroprotective, anti-glucosidase, and anti-HIV integrase properties. In one aspect, the pharmaceutical composition is delivered intranasally.

  本文描述了具有式(I)至(VIII)的化合物、其盐或其组合物以及包含一种或多种这些化合物的药物组合物，用于治疗HIV和HIV引起的神经退行性效应。本文还提供了抑制 HIV-1、治疗大脑中潜伏的 HIV 以及预防 HIV 介导的认知能力下降和 HIV 痴呆症的方法和试剂盒，包括施用具有式（I）至（VIII）的化合物和包含具有这些式的化合物的药物组合物。具有式 I 至式 VIII 的化合物是姜黄素类似物，其优点是具有抗逆转录病毒、神经保护、抗葡萄糖苷酶和抗 HIV 整合酶的特性。在一个方面，药物组合物经鼻内给药。
• SAR Studies on Curcumin’s Pro-inflammatory Targets: Discovery of Prenylated Pyrazolocurcuminoids as Potent and Selective Novel Inhibitors of 5-Lipoxygenase
  作者：Andreas Koeberle、Eduardo Muñoz、Giovanni B. Appendino、Alberto Minassi、Simona Pace、Antonietta Rossi、Christina Weinigel、Dagmar Barz、Lidia Sautebin、Diego Caprioglio、Juan A. Collado、Oliver Werz

  DOI：10.1021/jm500308c

  日期：2014.7.10

  The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (ie., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kappa B, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.