4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone | 1394245-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone
• 英文别名: isoquinolinequinone；Methyl 3-methyl-5,8-dioxoisoquinoline-4-carboxylate；methyl 3-methyl-5,8-dioxoisoquinoline-4-carboxylate
• CAS: 1394245-59-0
• 化学式: C₁₂H₉NO₄
• 分子量: 231.208
• InChiKey: VVQSGZAVZAHUBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  73.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone 在 N-溴代丁二酰亚胺(NBS) 、 cerium(III) chloride heptahydrate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 1.8h， 生成 7-bromo-6-(4-methoxyphenyl)amino-4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone
  参考文献：
  名称：

  新型苯氨基异喹啉醌对癌细胞系的合成和体外抗增殖活性。

  摘要：

  合成了多种苯氨基异喹啉醌并测试了它们对三种人类肿瘤来源的癌细胞系的抗增殖活性。新的氨基醌是通过酸诱导的胺化和溴化反应从 4-甲氧基羰基-3-甲基异喹啉-5,8-醌 (1) 制备的。根据醌核上取代苯氨基的位置和供体能力，观察到抗增殖活性的显着差异。取代基对生物活性的影响根据供体-受体相互作用进行了讨论，通过氨基醌的氧化还原特性进行了评估。

  DOI：

  10.3390/molecules18010721
• 作为产物：
  描述：

  2,5-二羟基苯甲醛 、 methyl (E)-3-aminocrotonate 在 magnesium sulfate 、 silver(l) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以86%的产率得到4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone
  参考文献：
  名称：

  Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones

  摘要：

  报道了 4-甲氧基羰基-3-甲基异喹啉醌 (1) 及其各种醌核上带有氨基、烷基氨基和卤素基团的取代产物的合成。使用 MTT 比色法在体外评估了 6-、7- 和 6,7- 取代的异喹啉醌系列的细胞毒性活性。所有新合成的化合物均对 MRC-5 健康肺成纤维细胞和四种人类肿瘤细胞系：AGS 胃腺癌、SK-MES-1 肺细胞、J82 膀胱癌和 HL-60 白血病细胞表现出中等到高效力。在该系列中，化合物4b、12和13对人胃腺癌、人肺癌和人膀胱癌细胞表现出令人感兴趣的抗肿瘤活性。 7-Amino-6-bromoisoquinoline-5,8-quinone (13) 被发现是针对测试的癌细胞系最有希望的活性化合物，IC50 值在 0.21−0.49 mM 范围内，低于抗癌剂依托泊苷用作参考。

  DOI：

  10.3390/molecules17067042

文献信息

• Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone–Amino Acid Derivatives
  作者：Jaime Valderrama、Virginia Delgado、Sandra Sepúlveda、Julio Benites、Cristina Theoduloz、Pedro Buc Calderon、Giulio Muccioli

  DOI：10.3390/molecules21091199

  日期：——

  methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure–activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate

  从 3-甲基-4-甲氧基羰基异喹啉-5,8-醌和多种l-和d-α-氨基酸甲酯合成了多种带有α-氨基酸部分的氨基异喹啉-5,8-醌。通过使用（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑鎓溴化物）（MTT）测定法评估该系列成员对正常和癌细胞系的细胞毒活性。从目前的研究来看，构效关系表明氨基酸片段的位置和结构在细胞毒性作用中起着重要作用。观察到中等至高的细胞毒活性，并且来自 l-丙氨酸、l-亮氨酸、l-苯丙氨酸和 d-苯丙氨酸的四个成员被选为有前途的化合物，其 IC50 范围为 0.5 至 6.25 μM，并且具有良好的选择性指数 (≥2.24)。
• Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach
  作者：Juana Ibacache、Judith Faundes、Margarita Montoya、Sophia Mejías、Jaime Valderrama

  DOI：10.3390/molecules23020439

  日期：——

  The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4’-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC50 = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC50 = 3.67; SI = 0.32) and taxol (mean IC50 = 0.35; SI = 0.91) employed as reference anticancer drugs.

  报告基于苯胺基异喹啉醌支架合成了五种新型同二聚体。在这些孪生药物衍生物中，苯胺基喹啉醌药基的两个单元通过亚甲基间隔相连。异喹啉醌与 4,4'-二氨基二苯甲烷通过一连串的两个氧化胺化反应形成了二聚体。同二聚体的初步体外筛选显示，它们对 MDA-MB-21 乳腺癌和 B16-F10 小鼠转移性黑色素瘤细胞系具有中等到较高的细胞毒性活性。不对称同源二聚体 15 脱颖而出，因为它在亚摩尔浓度下具有很强的细胞毒性，而且与作为参考抗癌药物的依托泊苷（平均 IC50 = 3.67；SI = 0.32）和紫杉醇（平均 IC50 = 0.35；SI = 0.91）相比，具有很高的选择性指数（平均 IC50 = 0.37 μM；SI = 6.97）。
• Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones
  作者：Virginia Delgado、Andrea Ibacache、Cristina Theoduloz、Jaime A. Valderrama

  DOI：10.3390/molecules17067042

  日期：——

  The synthesis of 4-methoxycarbonyl-3-methylisoquinolinequinone (1) and a variety of its substitution products with amino-, alkylamino and halogen groups on the quinone nucleus is reported. The series of 6-, 7- and 6,7-subtituted isoquinolinequinones were evaluated in vitro for their cytotoxic activity using the MTT colorimetric method. All the newly synthesized compounds showed moderate to high potency against MRC-5 healthy lung fibroblasts and four human tumor cell lines: AGS gastric adenocarcinoma, SK-MES-1 lung, J82 bladder carcinoma, and HL-60 leukemia cells. Among the series, compounds 4b, 12 and 13 exhibited interesting antitumor activity against human gastric adenocarcinoma, human lung and human bladder carcinoma cancer cells. 7-Amino-6-bromoisoquinoline-5,8-quinone (13) was found to be the most promising active compound against the tested cancer cell lines, with IC50 values in the 0.21−0.49 mM range, lower than the anti-cancer agent etoposide used as reference.

  报道了 4-甲氧基羰基-3-甲基异喹啉醌 (1) 及其各种醌核上带有氨基、烷基氨基和卤素基团的取代产物的合成。使用 MTT 比色法在体外评估了 6-、7- 和 6,7- 取代的异喹啉醌系列的细胞毒性活性。所有新合成的化合物均对 MRC-5 健康肺成纤维细胞和四种人类肿瘤细胞系：AGS 胃腺癌、SK-MES-1 肺细胞、J82 膀胱癌和 HL-60 白血病细胞表现出中等到高效力。在该系列中，化合物4b、12和13对人胃腺癌、人肺癌和人膀胱癌细胞表现出令人感兴趣的抗肿瘤活性。 7-Amino-6-bromoisoquinoline-5,8-quinone (13) 被发现是针对测试的癌细胞系最有希望的活性化合物，IC50 值在 0.21−0.49 mM 范围内，低于抗癌剂依托泊苷用作参考。
• Synthesis and in Vitro Antiproliferative Activity of New Phenylaminoisoquinolinequinones against Cancer Cell Lines
  作者：Virginia Delgado、Andrea Ibacache、Verónica Arancibia、Cristina Theoduloz、Jaime Valderrama

  DOI：10.3390/molecules18010721

  日期：——

  phenylaminoisoquinolinequinones were synthesized and tested for their antiproliferative activity against three human-tumor derived cancer cell lines. The new aminoquinones were prepared from 4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone (1) via acid-induced amination and bromination reactions. Remarkable differences in antiproliferative activity were observed depending upon the location and donor capacity

  合成了多种苯氨基异喹啉醌并测试了它们对三种人类肿瘤来源的癌细胞系的抗增殖活性。新的氨基醌是通过酸诱导的胺化和溴化反应从 4-甲氧基羰基-3-甲基异喹啉-5,8-醌 (1) 制备的。根据醌核上取代苯氨基的位置和供体能力，观察到抗增殖活性的显着差异。取代基对生物活性的影响根据供体-受体相互作用进行了讨论，通过氨基醌的氧化还原特性进行了评估。