Radester

• 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: Radester
• 英文别名: 1-(5-formamido-2-methoxy-3,6-dioxocyclohexa-1,4-dien-1-yl)propan-2-yl 5-chloro-2,4-dihydroxybenzoate
• 化学式: C₁₈H₁₆ClNO₈
• 分子量: 409.78
• InChiKey: WJOCXYVCMMPHIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-甲氧基对苯二酚 在 platinum(IV) oxide 、 palladium diacetate 硝酸铵 、 4-二甲氨基吡啶 、 正丁基锂 、 三甲基氯硅烷 、 氢气 、 sodium hydride 、 N,N'-二环己基碳二亚胺 、 三氟乙酸酐 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 37.08h， 生成 Radester
  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。
• Macrocyclic compounds useful as inhibitors of kinases and HSP90
  申请人：Winssinger Nicolas

  公开号：US20080146545A1

  公开（公告）日：2008-06-19

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin邻苯二酚内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP 90）的抑制剂。还公开了包含有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
  申请人：WINSSINGER Nicolas

  公开号：US20120077775A1

  公开（公告）日：2012-03-29

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin酚羧酸内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP90）的抑制剂。还公开了含有有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• Macrocyclic prodrug compounds useful as therapeutics
  申请人：Nexgenix Pharmaceuticals

  公开号：EP2254880B1

  公开（公告）日：2016-08-17
• METHODS OF TREATING VIRAL INFECTION
  申请人：Frydman Judith

  公开号：US20100093824A1

  公开（公告）日：2010-04-15

  The present invention provides methods of treating an RNA viral infection, generally involving administering an agent that reduces the activity of a host cell protein required for maturation of a viral protein, where the emergence of variant virus resistant to the agent is reduced. The present invention further provides combination therapies for viral infection, involving administration of two or more agents that reduce the activity of a host cell protein required for maturation of a viral protein.