2-methoxy-1,4-bis(methoxymethoxy)benzene | 131223-60-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-methoxy-1,4-bis(methoxymethoxy)benzene
• 英文别名: Benzene, 2-methoxy-1,4-bis(methoxymethoxy)-
• CAS: 131223-60-4
• 化学式: C₁₁H₁₆O₅
• 分子量: 228.245
• InChiKey: WCGOLRWLNWIPCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methoxy-1,4-bis(methoxymethoxy)benzene 在 pyridinium hydrobromide perbromide 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 0.42h， 以89%的产率得到1-溴-4-甲氧基-2,5-二(甲氧基甲氧基)苯
  参考文献：
  名称：

  Synthesis, Antifungal Activity, and Structure−Activity Relationships of Coruscanone A Analogues

  摘要：

  Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. A series of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity. Structure-activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding.

  DOI：

  10.1021/jm061123i
• 作为产物：
  描述：

  2-甲氧基对苯二酚 、 氯甲基甲基醚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以94%的产率得到2-methoxy-1,4-bis(methoxymethoxy)benzene
  参考文献：
  名称：

  新型腺苷衍生的隐孢子虫肌苷 5'-单磷酸脱氢酶抑制剂。

  摘要：

  我们通过基于荧光素酶的高通量筛选从北海道大学化学图书馆发现了具有对醌酰胺部分（1 和 2）的环烷型腺苷衍生物作为隐孢子虫肌苷 5'-单磷酸脱氢酶 (CpIMPDH) 的弱抑制剂。为了获得更有效的抑制剂，我们合成了四种不含环芳环的新衍生物 (3-6)。NH 衍生物 3 和 5 在二硫苏糖醇 (DTT) 存在下表现出更强的活性（分别为 24.4 和 11.1 μM），而 N-甲基衍生物 4 在没有 DTT 的情况下表现出更强的活性（2.1 μM）。化合物 3 和 4 的构象分析表明 NH 酰胺 3 以 DTT 介导的方式与 IMP 结合位点结合。

  DOI：

  10.1038/s41429-019-0199-3

文献信息

• Radester, a Novel Inhibitor of the Hsp90 Protein Folding Machinery
  作者：Gang Shen、Brian S. J. Blagg

  DOI：10.1021/ol050580a

  日期：2005.5.1

  and geldanamycin are potent inhibitors of the Hsp90 protein folding machinery. Radester is a hybrid composed of radicicol's resorcinol ring and geldanamycin's quinone through an isopropyl ester. Radester was prepared, and the cytotoxicity of it and the corresponding hydroquinone were determined in MCF-7 breast cancer cells to be 13.9 and 7.1 microM, respectively. Protein degradation assays were performed

  [反应：请参见文字]。抗肿瘤抗生素radicicol和geldanamycin是Hsp90蛋白折叠机制的有效抑制剂。Radester是由Radcicol的间苯二酚环和Geldanamycin的醌通过异丙酯组成的杂化物。制备了Radester，并确定其在MCF-7乳腺癌细胞中的细胞毒性分别为13.9和7.1 microM。对Hsp90依赖的客户蛋白Her-2和Raf进行蛋白降解测定，以将Hsp90抑制与细胞毒性相关联。
• Heat shock protein 90 inhibitors
  申请人：Blagg Brian

  公开号：US20060089495A1

  公开（公告）日：2006-04-27

  Novel compounds useful for inhibiting the 90 kDa heat shock proteins containing a quinone-like moiety and a di-hydroxy phenol like moiety, similar to geldanamycin and radicicol.

  新型化合物对抑制含有类似醌类结构和二羟基酚类结构的90千道尔顿热休克蛋白具有用途，类似于格尔德霉素和拉迪考尔。
• Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases
  作者：Emilie Evain-Bana、Lucie Schiavo、Christophe Bour、Don Antoine Lanfranchi、Simone Berardozzi、Francesca Ghirga、Denyse Bagrel、Bruno Botta、Gilles Hanquet、Mattia Mori

  DOI：10.1080/14756366.2016.1238364

  日期：2017.1.1

  phosphatases are a valuable target for the development of small molecule inhibitors of therapeutic relevance. Here, we used an integrated strategy mixing organic chemistry with biological investigation and molecular modeling to study novel quinonoid derivatives as CDC25 inhibitors. The most promising molecules proved to inhibit CDC25 isoforms at single digit micromolar concentration, becoming valuable

  细胞分裂周期的25种磷酸酶（CDC25A，B和C； EC 3.1.3.48）是人类细胞中细胞周期的关键调节剂。它们的异常表达与各种类型的癌症的发生和发展以及不良的临床预后有关。因此，CDC25磷酸酶是开发具有治疗意义的小分子抑制剂的有价值的靶标。在这里，我们采用了一种将有机化学与生物学研究和分子建模相结合的综合策略，来研究新型醌类衍生物作为CDC25抑制剂。事实证明，最有前途的分子在一位数微摩尔浓度下能抑制CDC25同工型，成为化学生物学研究中的宝贵工具，并且是进一步优化的有利条件。[公式：见文字]。
• Substituted benzopyrans as selective estrogen receptor-beta agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP1790644A1

  公开（公告）日：2007-05-30

  The present invention relates to substituted benzopyran derivatives, stereoisomers, and pharmaceutical acceptable salts thereof and processes for the preparation of the same. The compounds of the present invention are useful as Estrogen Receptor β agonists. Such agonists are useful for the treating Estrogen Receptor β mediated diseases such as prostate cancer.

  本发明涉及取代的苯并吡喃衍生物、立体异构体、其药物可接受盐及其制备工艺。本发明的化合物可用作雌激素受体β激动剂。此类激动剂可用于治疗雌激素受体β介导的疾病，如前列腺癌。
• Design, Synthesis, and StructureActivity Relationships for Chimeric Inhibitors of Hsp90
  作者：Gang Shen、Mingwen Wang、Timothy R. Welch、Brian S. J. Blagg

  DOI：10.1021/jo061054f

  日期：2006.9.1

  Inhibition of the 90 kDa heat shock protein (Hsp90) family of molecular chaperones represents a promising new chemotherapeutic approach toward the treatment of several cancers. Previous studies have demonstrated that the natural products, radicicol and geldanamycin, are potent inhibitors of the Hsp90 N-terminal ATP binding site. The cocrystal structures of these molecules bound to Hsp90 have been determined, and through molecular modeling and superimposition of these ligands, hybrids of radicicol and geldanamycin have been designed. A series of macrocylic chimeras of radicicol and geldanamycin and the corresponding seco-agents have been prepared and evaluated for both antiproliferative activity and their ability to induce Hsp90-dependent client protein degradation.