3,4-dihydro-8-hydroxy-2,2-dimethyl-2H-benzo[h]chromene-5,6-dione | 305836-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 3,4-dihydro-8-hydroxy-2,2-dimethyl-2H-benzo[h]chromene-5,6-dione
• 英文别名: 8-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione；8-hydroxy-β-lapachone；8-Hydroxy-beta-lapachone；8-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione
• CAS: 305836-34-4
• 化学式: C₁₅H₁₄O₄
• 分子量: 258.274
• InChiKey: IKNHVSDGNYBZKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 甲烷磺酸 、 potassium tert-butylate 、 氧气 、 三溴化硼 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 0.05h， 生成 3,4-dihydro-8-hydroxy-2,2-dimethyl-2H-benzo[h]chromene-5,6-dione
  参考文献：
  名称：

  β-Lapachone analogs with enhanced antiproliferative activity

  摘要：

  In this study, we describe the synthesis of a series of alpha- and beta-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-beta-lapachone as lead with enhanced activity over the parent drug beta-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to beta-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-beta-lapachone. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.008

文献信息

• Quinones as disease therapies
  申请人：SLIL Biomedical Corporation

  公开号：US06482943B1

  公开（公告）日：2002-11-19

  Novel quinones are provided, as well as compositions comprising these novel quinones. Methods of using the novel quinones in treatment of various indications including cancer are also provided.

  本发明提供了新型的醌类物质，以及包含这些新型醌类物质的组合物。还提供了使用这些新型醌类物质治疗各种疾病，包括癌症的方法。
• Synthetic methods for the preparation of ARQ 501 (β-Lapachone) human blood metabolites
  作者：Rui-Yang Yang、Darin Kizer、Hui Wu、Erika Volckova、Xiu-Sheng Miao、Syed M. Ali、Manish Tandon、Ronald E. Savage、Thomas C.K. Chan、Mark A. Ashwell

  DOI：10.1016/j.bmc.2008.03.073

  日期：2008.5

  ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione), a synthetic version of beta-Lapachone, is a promising anti-cancer agent currently in multiple Phase II clinical trials. Promising anti-cancer activity was observed in Phase I and Phase II trials. Metabolism by red blood cells of drugs is an understudied area of research and the metabolites arising from oxidative ring opening (M2 and M3), decarbonylation/ ring contraction (M5), and decarbonylation/ oxidation (M4 and M6) of ARQ 501 offer a unique opportunity to provide insight into these metabolic processes. Since these metabolites were not detected in in vitro incubations of ARQ 501 with liver microsomes and were structurally diverse, confirmation by chemical synthesis was considered essential. In this report, we disclose the synthetic routes employed and the characterization of the reference standards for these blood metabolites as well as additional postulated structures, which were not confirmed as metabolites. (C) 2008 Elsevier Ltd. All rights reserved.
• US7253207B2
  申请人：——

  公开号：US7253207B2

  公开（公告）日：2007-08-07
• β-Lapachone analogs with enhanced antiproliferative activity
  作者：Carla Ríos-Luci、Evelyn L. Bonifazi、Leticia G. León、Juan C. Montero、Gerardo Burton、Atanasio Pandiella、Rosana I. Misico、José M. Padrón

  DOI：10.1016/j.ejmech.2012.04.008

  日期：2012.7

  In this study, we describe the synthesis of a series of alpha- and beta-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-beta-lapachone as lead with enhanced activity over the parent drug beta-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to beta-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-beta-lapachone. (C) 2012 Elsevier Masson SAS. All rights reserved.