bis((3-carboxy-2-methyl-furan-5-yl)methyl)sulfane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: bis((3-carboxy-2-methyl-furan-5-yl)methyl)sulfane
• 英文别名: bis((3-carboxy-2-methylfuran-5-yl)methyl)sulfane；ZINC00041425；ST092803；5-[(4-Carboxy-5-methylfuran-2-yl)methylsulfanylmethyl]-2-methylfuran-3-carboxylic acid
• 化学式: C₁₄H₁₄O₆S
• 分子量: 310.328
• InChiKey: NZYGSXIHAOWTMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 2-(chloromethyl)-5-methylfuran-4-carboxylate 在 sodiumsulfide nonahydrate 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 bis((3-carboxy-2-methyl-furan-5-yl)methyl)sulfane
  参考文献：
  名称：

  一种新型的双呋喃支架，可稳定运甲状腺素蛋白和抑制淀粉样蛋白

  摘要：

  据报道，为抑制转甲状腺素蛋白淀粉样蛋白形成的高效率而设计的新型双呋喃支架的设计与合成。体外结果表明，发现的化合物比塔法米第更有效地抑制淀粉样蛋白的形成，尽管它具有较低的分子量和亲脂性，但它目前是一种用于治疗家族性淀粉样多发性神经病（FAP）的药物。而且，离体在正常血浆和FAP Val30Met-运甲状腺素蛋白载体的人血浆中进行的该系列中最强抑制剂的实验，显示出显着的亲和力和选择性。根据越来越多的证据表明运甲状腺素蛋白的稳定性不仅是运甲状腺素蛋白淀粉样蛋白和几种相关合并症的关键因素，而且在阿尔茨海默氏病中也作为关键因素，讨论了该化合物进一步开发所面临的希望和挑战。

  DOI：

  10.1016/j.ejmech.2016.02.074

文献信息

• [EN] BIS-FURAN DERIVATIVES AS TRANSTHYRETIN (TTR) STABILIZERS AND AMYLOID INHIBITORS FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY (FAP)<br/>[FR] DÉRIVÉS DE BIS-FURANE EN TANT QUE STABILISATEURS DE LA TRANSTHYRÉTINE (TTR) ET INHIBITEURS D'AMYLOÏDE POUR LE TRAITEMENT DE LA POLYNEUROPATHIE AMYLOÏDE FAMILIALE (FAP)
  申请人：BSIM2 – BIOMOLECULAR SIMULATIONS LDA

  公开号：WO2016203402A1

  公开（公告）日：2016-12-22

  The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloid polyneuropathy (FAP), despite their lower molecular weight and lipophilicity. Moreover, ex vivo experiments with the strongest inhibitor in the series, conducted in human blood plasma from normal and FAP Val30Met-transthyretin carriers, disclose remarkable affinity and selectivity profiles. The promises and challenges facing further development of this compound are discussed under the light of increasing evidence implicating transthyretin stability as a key factor not only in transthyretin amyloidoses and several associated co-morbidities, but also in Alzheimer's disease.

  报道了一种针对高效抑制前甲状腺素淀粉样形成而量身定制的新型双呋喃骨架的设计和合成。体外结果显示，尽管其分子量和亲脂性较低，但发现的化合物比目前用于治疗家族性淀粉样多发性神经病（FAP）的他法米特更有效地抑制淀粉样形成。此外，使用该系列中最强的抑制剂在人类血浆中进行的外体实验，从正常人和FAP Val30Met-前甲状腺素携带者中揭示出显著的亲和力和选择性特性。在越来越多的证据表明前甲状腺素稳定性不仅是前甲状腺素淀粉样病和几种相关共病的关键因素，而且也是阿尔茨海默病的关键因素的光下，讨论了进一步开发该化合物所面临的希望和挑战。
• Bis-furan derivatives as transthyretin (TTR) stabilizers and amyloid inhibitors for the treatment of familial amyloid polyneuropathy (FAP)
  申请人：BSIM Therapeutics, S.A.

  公开号：US10377729B2

  公开（公告）日：2019-08-13

  The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloid polyneuropathy (FAP), despite their lower molecular weight and lipophilicity. Moreover, ex vivo experiments with the strongest inhibitor in the series, conducted in human blood plasma from normal and FAP Val30Met-transthyretin carriers, disclose remarkable affinity and selectivity profiles. The promises and challenges facing further development of this compound are discussed under the light of increasing evidence implicating transthyretin stability as a key factor not only in transthyretin amyloidoses and several associated co-morbidities, but also in Alzheimer's disease.

  本研究报告设计并合成了一种新型双呋喃支架，可高效抑制转甲状腺素淀粉样蛋白的形成。体外实验结果表明，与目前用于治疗家族性淀粉样多神经病（FAP）的药物他伐米迪相比，所发现的化合物是更有效的淀粉样蛋白形成抑制剂，尽管它们的分子量和亲油性更低。此外，在正常人和 FAP Val30Met 转甲状腺素携带者的人体血浆中对该系列中最强的抑制剂进行的体内外实验显示，它们具有显著的亲和性和选择性。有越来越多的证据表明，转甲状腺素稳定性不仅是转甲状腺素淀粉样变性和一些相关并发症的关键因素，而且也是阿尔茨海默病的关键因素，因此我们讨论了进一步开发这种化合物的前景和挑战。
• BIS-FURAN DERIVATIVES AS TRANSTHYRETIN (TTR) STABILIZERS AND AMYLOID INHIBITORS FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY (FAP)
  申请人：BSIM2 - Biomolecular Simulations, S.A.

  公开号：EP3307723A1

  公开（公告）日：2018-04-18
• COMPOUNDS THAT INHIBIT HUMAN DNA LIGASES AND METHODS OF TREATING CANCER
  申请人：TOMKINSON Alan E.

  公开号：US20100099683A1

  公开（公告）日：2010-04-22

  Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.
• Compounds that inhibit human DNA ligases and methods of treating cancer
  申请人：University of Maryland, Baltimore

  公开号：US20140113891A1

  公开（公告）日：2014-04-24

  Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.