2-(2-Carboxy-ethyl)-3-chloro-4,6-dihydroxy-benzoic acid 2-(3-amino-6-methoxy-2,5-bis-methoxymethoxy-phenyl)-1-methyl-ethyl ester | 884861-60-3

• 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: 2-(2-Carboxy-ethyl)-3-chloro-4,6-dihydroxy-benzoic acid 2-(3-amino-6-methoxy-2,5-bis-methoxymethoxy-phenyl)-1-methyl-ethyl ester
• 英文别名: 3-[2-[1-[5-Amino-2-methoxy-3,6-bis(methoxymethoxy)phenyl]propan-2-yloxycarbonyl]-6-chloro-3,5-dihydroxyphenyl]propanoic acid
• CAS: 884861-60-3
• 化学式: C₂₄H₃₀ClNO₁₁
• 分子量: 543.955
• InChiKey: AXFKOUDDUIAWNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(2-Carboxy-ethyl)-3-chloro-4,6-dihydroxy-benzoic acid 2-(3-amino-6-methoxy-2,5-bis-methoxymethoxy-phenyl)-1-methyl-ethyl ester 在 palladium on activated charcoal 三甲基氯硅烷 、 air 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 7-Chloro-8,10-dihydroxy-17-methoxy-14-methyl-13-oxa-2-azatricyclo[14.3.1.06,11]icosa-1(19),6(11),7,9,16-pentaene-3,12,18,20-tetrone
  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 palladium on activated charcoal 硝酸铵 、 4-二甲氨基吡啶 、 sodium chlorite 、 sodium periodate 、 sodium dihydrogenphosphate 、 四氧化锇 、 正丁基锂 、 2-甲基-2-丁烯 、 氢气 、 sodium hydride 、 N,N'-二环己基碳二亚胺 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 0.33h， 生成 2-(2-Carboxy-ethyl)-3-chloro-4,6-dihydroxy-benzoic acid 2-(3-amino-6-methoxy-2,5-bis-methoxymethoxy-phenyl)-1-methyl-ethyl ester
  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

• 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.
• 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.