2-羟甲基-4,7-二甲氧基苯并咪唑 | 103151-22-0

• 物质功能分类: 有机原料 - 醇、酚、酚醇类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-羟甲基-4,7-二甲氧基苯并咪唑
• 英文名称: 2-hydroxymethyl-4,7-dimethoxy benzimidazole
• 英文别名: 4,7-dimethoxy-2-hydroxymethylbenzimidazole；(4,7-dimethoxybenzimidazol-2-yl)methanol；(4,7-dimethoxy-1H-benzimidazol-2-yl)-methanol；1H-Benzimidazole-2-methanol, 4,7-dimethoxy-；(4,7-dimethoxy-1H-benzimidazol-2-yl)methanol
• CAS: 103151-22-0
• 化学式: C₁₀H₁₂N₂O₃
• 分子量: 208.217
• InChiKey: KDSNURLLTUKKSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-羟甲基-4,7-二甲氧基苯并咪唑 在 silver(II) oxide 、 氨 、 硝酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 10.16h， 生成 2-[[Amino-[bis(2-bromoethyl)amino]phosphoryl]oxymethyl]-1-methylbenzimidazole-4,7-dione
  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-2,3-二硝基苯 在 盐酸 、 乙醇 、 铂 作用下， 生成 2-羟甲基-4,7-二甲氧基苯并咪唑
  参考文献：
  名称：

  Syntheses of Dimethoxybenzimidazoles, Dihydroxybenzimidazoles and Imidazo-p-benzoquinones

  摘要：

  DOI：

  10.1021/jo01092a017

文献信息

• Heterocyclic quinones with potential antitumor activity. 2. Synthesis and antitumor activity of some benzimidazole-4,7-dione derivatives
  作者：Ippolito Antonini、Francesco Claudi、Gloria Cristalli、Palmarisa Franchetti、Mario Grifantini、Sante Martelli

  DOI：10.1021/jm00396a041

  日期：1988.1

  series of benzimidazole-4,7-dione derivatives, bearing substituents at positions 1, 2, 5, and 6 of the benzimidazole ring, has been synthesized and tested for antitumor activity in vivo on P388 leukemia. Some of the synthesized compounds show significant antitumor activity, associated with high toxicity, however. Compounds 7, 18, and 27 show the highest antitumor activity in this series, whereas 17

  已经合成了一系列在苯并咪唑环的1、2、5和6位带有取代基的苯并咪唑-4,7-二酮衍生物，并在体内测试了其对P388白血病的抗肿瘤活性。然而，一些合成的化合物显示出显着的抗肿瘤活性，并伴有高毒性。化合物7、18和27在此系列中显示出最高的抗肿瘤活性，而17、19和22几乎没有活性。这些醌的一些假设的生物学前体没有抗肿瘤活性。讨论了一些构效关系。
• Synthesis of Analogs of Hoechst 33258 Designed for Altered Base and Sequence Recognition
  作者：Ashok K. Sing、J. W. Lown

  DOI：10.1080/00397910008087106

  日期：2000.3

  Abstract The syntheses of various analogs of the minor groove binding agent Hoechst 33258 I are described to explore their potential of selective helicase blockade and anticancer activity. The target compounds II a,b,c and III a,b,c were obtained by condensation of the appropriate functionalized ortho-diamines and substituted benzimidazole carboxaldehydes in nitrobenzene.

  摘要 描述了小沟结合剂 Hoechst 33258 I 的各种类似物的合成，以探索其选择性解旋酶阻断和抗癌活性的潜力。目标化合物II a、b、c和III a、b、c通过适当的官能化邻二胺和取代的苯并咪唑甲醛在硝基苯中的缩合获得。
• Synthesis of Pyrrolo- and Pyrido-[1,2-<i>a</i>]benzimidazolequinone Anti-tumor Agents Containing a Fused Cyclopropane Ring
  作者：Fawaz Aldabbagh、John O’Shaughnessy

  DOI：10.1055/s-2005-861832

  日期：——

  A cyclopropane ring has been fused onto tetrahydropyrrolo- and tetrahydropyrido-[1,2-a]-benzimidazoles and -benzimidazolequinones via the cycloaddition of diazomethines generated from the thermolysis of N-(allyl and but-3-enyl)benzimidazole-2-Eschenmoser hydrazones (aziridinyl imines). At lower temperatures, the 1,3-dipolar [3 + 2] cycloadduct was obtained for only the N-allylbenzimidazole-2-Eschenmoser

  通过 N-(烯丙基和丁-3-烯基)苯并咪唑-2-Eschenmoser 热解产生的重氮亚甲基环加成，环丙烷环已稠合到四氢吡咯并-和四氢吡啶并-[1,2-a]-苯并咪唑和苯并咪唑醌上腙（氮丙啶亚胺）。在较低温度下，仅 N-烯丙基苯并咪唑-2-Eschenmoser 腙得到 1,3-偶极 [3 + 2] 环加合物。
• Synthesis of Benzimidazolequinone Analogue of Cyclopropamitosene Antitumor Agents
  作者：Fawaz Aldabbagh、John O’Shaughnessy、Desmond Cunningham、Paul Kavanagh、Dónal Leech、Patrick McArdle

  DOI：10.1055/s-2004-831341

  日期：——

  The preparation of a pyrrolo[ 1,2-a]benzimidazole, pyrido[1,2-a]benzimidazole and pyrrolo[1,2-a]benzimidazolequinone containing a fused cyclopropane ring is reported. Their synthesis involved the thermolysis of the respective benzimidazole-2-Eschenmoser hydrazones (aziridinyl imines), which facilitated an intramolecular 1,3-dipolar cycloaddition. X-ray crystal structure of one [3+2] pyrazoline-cycloadduct

  报道了含有稠环丙烷环的吡咯并[1,2-a]苯并咪唑、吡啶并[1,2-a]苯并咪唑和吡咯并[1,2-a]苯并咪唑醌的制备。它们的合成涉及各自苯并咪唑-2-Eschenmoser 腙（氮丙啶基亚胺）的热解，这促进了分子内 1,3-偶极环加成。展示了一种 [3+2] 吡唑啉环加合物的 X 射线晶体结构。环丙吡咯并 [1,2-a] 苯并咪唑醌的 -1.052 V（相对于二茂铁）的氧化还原电位通过循环伏安法测定，表明单电子还原比丝裂霉素 C 或环丙酰胺更容易发生。
• Synthesis of Substituted Imidazo[4,5-b]pyridines as Analogues of the DNA Binding Fluorochrome Hoechst 33258
  作者：Ashok K. Singh、J. WilliamLown

  DOI：10.1080/00397919808004966

  日期：1998.11

  Abstract Various substituted imidazo[4,5-b]pyridine analogues of Hoechst 33258 have been synthesized to explore the potential of selective helicase blockade and anticancer activity. The target compounds II a, b & d were obtained by condensation of the appropriate functionalized diamine and substituted benzimidazole aldehydes in nitrobenzene.

  摘要 合成了 Hoechst 33258 的各种取代咪唑并 [4,5-b] 吡啶类似物，以探索选择性解旋酶阻断和抗癌活性的潜力。目标化合物IIa、b和d通过合适的官能化二胺和取代的苯并咪唑醛在硝基苯中的缩合获得。