1,4-dimethoxy-3-thiomethyl-2-hydroxymethylnaphthalene | 289896-39-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1,4-dimethoxy-3-thiomethyl-2-hydroxymethylnaphthalene
• 英文别名: 1,4-dimethoxy-2-hydroxymethyl-3-methylthionaphthalene；1,4-Dimethoxy-2-hydroxymethyl-3-methylsulfanylnaphthalene；(1,4-dimethoxy-3-methylsulfanylnaphthalen-2-yl)methanol
• CAS: 289896-39-5
• 化学式: C₁₄H₁₆O₃S
• 分子量: 264.345
• InChiKey: TWRJYNFVHYZFKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-dimethoxy-3-thiomethyl-2-hydroxymethylnaphthalene 在 ammonium cerium(IV) nitrate 、 氨 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.75h， 生成 amino-N,N-di-(2-chloroethyl)aminophosphoric acid (3-methylthio-1,4-naphthoquinone-2-ylmethyl) ester
  参考文献：
  名称：

  Development of Novel Quinone Phosphorodiamidate Prodrugs Targeted to DT-Diaphorase

  摘要：

  A series of naphthoquinone and benzimidazolequinone phosphorodiamidates has been synthesized and studied as potential cytotoxic prodrugs activated by DT-diaphorase. Reduction of the quinone moiety in the target compounds was expected to provide a pathway for expulsion of the phosphoramide mustard alkylating agent. All of the compounds synthesized were excellent substrates for purified human DT-diaphorase (k(cat)/K-m = 3 x 10(7) - 3 x 10(8) M-1 s(-1)). The naphthoquinones were toxic to both HT-29 and BE human colon cancer cell lines in a clonogenic assay; however, cytotoxicity did not correlate with DT-diaphorase activity in these cell lines. The benzimidazolequinone analogues were 1-2 orders of magnitude less cytotoxic than the naphthoquinone analogues. Chemical reduction of the naphthoquinone led to rapid expulsion of the phosphorodiamidate anion; in contrast, the benzimidazole reduction product was stable. Michael addition of glutathione and other sulfur nucleophiles provides an alternate mechanism for activation of the naphthoquinone phosphorodiamidates, and this mechanism may contribute to the cytotoxicity of these compounds.

  DOI：

  10.1021/jm000179o
• 作为产物：
  描述：

  1,4-二甲氧基-2-萘甲酸甲酯 在 lithium aluminium tetrahydride 、 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 4.5h， 生成 1,4-dimethoxy-3-thiomethyl-2-hydroxymethylnaphthalene
  参考文献：
  名称：

  Development of Novel Quinone Phosphorodiamidate Prodrugs Targeted to DT-Diaphorase

  摘要：

  A series of naphthoquinone and benzimidazolequinone phosphorodiamidates has been synthesized and studied as potential cytotoxic prodrugs activated by DT-diaphorase. Reduction of the quinone moiety in the target compounds was expected to provide a pathway for expulsion of the phosphoramide mustard alkylating agent. All of the compounds synthesized were excellent substrates for purified human DT-diaphorase (k(cat)/K-m = 3 x 10(7) - 3 x 10(8) M-1 s(-1)). The naphthoquinones were toxic to both HT-29 and BE human colon cancer cell lines in a clonogenic assay; however, cytotoxicity did not correlate with DT-diaphorase activity in these cell lines. The benzimidazolequinone analogues were 1-2 orders of magnitude less cytotoxic than the naphthoquinone analogues. Chemical reduction of the naphthoquinone led to rapid expulsion of the phosphorodiamidate anion; in contrast, the benzimidazole reduction product was stable. Michael addition of glutathione and other sulfur nucleophiles provides an alternate mechanism for activation of the naphthoquinone phosphorodiamidates, and this mechanism may contribute to the cytotoxicity of these compounds.

  DOI：

  10.1021/jm000179o

文献信息

• Quinone derivatives, pharmaceutical compositions, and uses thereof
  申请人：Kelley Mark R.

  公开号：US09089605B2

  公开（公告）日：2015-07-28

  This application describes quinone derivatives which target the redox site of Ape1/Ref1. Also included in the invention are pharmaceutical formulations containing the derivatives and therapeutic uses of the derivatives.

  本申请描述了靶向Ape1/Ref1的氧化还原位点的醌衍生物。本发明还包括含有该衍生物的药物配方和该衍生物的治疗用途。
• QUINONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Kelley Mark R.

  公开号：US20100297113A1

  公开（公告）日：2010-11-25

  This application describes quinone derivatives which target the redox site of Ape1/Ref1. Also included in the invention are pharmaceutical formulations containing the derivatives and therapeutic uses of the derivatives.

  这个应用描述了目标为Ape1/Ref1的氧化还原位点的醌衍生物。发明还包括含有这些衍生物的药物制剂和这些衍生物的治疗用途。
• Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)
  作者：Rodney L. Nyland、Meihua Luo、Mark R. Kelley、Richard F. Borch

  DOI：10.1021/jm9014857

  日期：2010.2.11

  The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Apel/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Apel can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Apel redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Apel. Benzoquinone and naphthoquinone analogues of the Apel-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Apel redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 mu M range.
• US7304046B2
  申请人：——

  公开号：US7304046B2

  公开（公告）日：2007-12-04
• US9089605B2
  申请人：——

  公开号：US9089605B2

  公开（公告）日：2015-07-28