1-(2-methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)propan-2-ol | 854261-03-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2-methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)propan-2-ol
• 英文别名: 1-[2-Methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl]propan-2-ol
• CAS: 854261-03-3
• 化学式: C₁₄H₂₁NO₈
• 分子量: 331.323
• InChiKey: RTYOXTSBRCWAGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(2-methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)propan-2-ol 在 platinum(IV) oxide 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 1-(3-benzamido-6-methoxy-2,5-bis(methoxymethoxy)phenyl)propan-2-yl 5-chloro-2,4-dihydroxybenzoate
  参考文献：
  名称：

  Design, Synthesis, and StructureActivity Relationships for Chimeric Inhibitors of Hsp90

  摘要：

  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.

  DOI：

  10.1021/jo061054f
• 作为产物：
  描述：

  2-甲氧基对苯二酚 在 硝酸铵 、 正丁基锂 、 sodium hydride 、 三氟乙酸酐 作用下， 以 乙腈 为溶剂， 反应 0.33h， 生成 1-(2-methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)propan-2-ol
  参考文献：
  名称：

  Design, Synthesis, and StructureActivity Relationships for Chimeric Inhibitors of Hsp90

  摘要：

  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.

  DOI：

  10.1021/jo061054f

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。
• Radanamycin, a macrocyclic chimera of radicicol and geldanamycin
  作者：Mingwen Wang、Gang Shen、Brian S.J. Blagg

  DOI：10.1016/j.bmcl.2006.01.086

  日期：2006.5

  Radicicol and geldanamycin are potent inhibitors of the Hsp90 protein folding machinery, which is an emerging target for the development of cancer chemotherapeutics. However, radicicol is inactive in vivo and geldanamycin suffers from its redox-active behavior that produces toxicity unrelated to Hsp90 inhibition. It was proposed that a chimeric molecule containing the resorcinol ring of radicicol and the quinone of geldanamycin could provide an opportunity to elucidate structure-activity relationships for both natural products and serve as a starting point for the development of more potent inhibitors. Synthesis of the macrocyclic chimera named radanamycin is reported along with the biological activity exhibited by this compound in MCF-7 breast cancer cells. (C) 2006 Elsevier Ltd. All rights reserved.
• Heat shock protein 90 inhibitors
  申请人：Blagg Brian

  公开号：US20070197787A1

  公开（公告）日：2007-08-23

  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.
• HEAT SHOCK PROTEIN 90 INHIBITORS
  申请人：Blagg Brian S.J.

  公开号：US20100099865A1

  公开（公告）日：2010-04-22

  Novel compounds useful for inhibiting the 90kDa heat shock proteins containing a quinone-like moiety and a di-hydroxy phenol like moiety, similar to geldanamycin and radicicol.
• US7208630B2
  申请人：——

  公开号：US7208630B2

  公开（公告）日：2007-04-24