1,5-bis-m-toluoylamino-anthraquinone | 75311-87-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1,5-bis-m-toluoylamino-anthraquinone
• 英文别名: 1,5-Bis-m-toluoylamino-anthrachinon；1,5-bis-[3-(methyl)benzoylamido]-9,10-anthracenedione；3-methyl-N-[5-[(3-methylbenzoyl)amino]-9,10-dioxoanthracen-1-yl]benzamide
• CAS: 75311-87-4
• 化学式: C₃₀H₂₂N₂O₄
• 分子量: 474.516
• InChiKey: ZLHJKTRNYILSGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,5-二氨基蒽醌 、 间甲基苯甲酰氯 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以63%的产率得到1,5-bis-m-toluoylamino-anthraquinone
  参考文献：
  名称：

  Synthesis and Antitumor Evaluation of Symmetrical 1,5-Diamidoanthraquinone Derivatives as Compared to Their Disubstituted Homologues

  摘要：

  一系列对称的1,5-二氨基蒽醌衍生物已被合成，并研究了其对多种癌细胞系的细胞抑制活性。初步的结构-活性关系得到了建立。结果显示，化合物5和18在1.24-1.75 μM时对Hepa G2细胞系表现出显著的细胞毒性；化合物5、16和18在0.14-1.82 μM时对2.2.15细胞系表现出细胞毒性，通过XTT比色法进行了测定。两种结构相关的化合物，米托蒽醌和阿霉素，被作为阳性对照进行平行测试。此外，发现化合物5和18在对人肝癌细胞系的活性上比米托蒽醌更强，而与阿霉素的活性相当。在上述化合物中，化合物18对2.2.15细胞的活性最强。我们证明了蒽醌基团对于活性是必不可少的，且较少空间位阻的取代基有助于增强体外活性。讨论了氨基蒽醌类化合物作为潜在抗癌剂的细胞毒性影响。我们进一步阐明了这一类化合物的药效基团的性质，为结构-活性关系提供了合理依据。

  DOI：

  10.1248/cpb.54.458

文献信息

• Synthesis and pharmaceuticals of novel bis-substituted anthraquinone derivatives
  申请人：Huang Hsu-Shan

  公开号：US20050009924A1

  公开（公告）日：2005-01-13

  This invention relates to novel anthraquinone compounds useful in the treatment of allergic, inflammatory conditions, antioxidant, tumor condition, stem cell application, tissue engineering, applied in treating age-associate tissue degeneration, reverse organ failure in chronic high-turnover disease and therapeutic compositions containing such compounds. The compounds of the present invention are 1,4-, 1,5- and 1,8-difunctionalized anthraquinones or analogs thereof. According to the practice of the invention, there are provided bis-symmetrical substituted anthraquinone compounds according to formula I: wherein R1, R2, R3 and R4 present a straight, aminoalkylamino side chains or branched chain alkyl group having 1 to 6 carbons which may be substituted with one or more groups of R5, or R1, R2, R3 and R4 present phenyl or benzyl which may be substituted with one or two groups of R6; wherein R5 is selected from the group consisting of halogen, —RNH 2 , —RNH 2 R, —ROH, —NO 2 , —OCH 3 , —OCH 2 CH 3 , and —OCH 2 CH 2 CH 3 ; and wherein R6 is selected from the group consisting of a straight or branched chain alkyl group having 1 to 4 carbons, halogen, —RNH 2 , —RNH 2 R, —ROH, —NO 2 , —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —CH 2 Br, —CH 2 Cl, —CH 2 OH, —C(CH 3 ) 3 , —(CH 2 ) 2 0H, —(CH 2 ) 3 OH, —(CH 2 ) 4 OH, —CH 2 NH 2 , —(CH 2 ) 2 NH 2 , —(CH 2 ) 3 NH 2 , —(CH 2 ) 4 NH 2 , —(CH 2 ) 5 NH 2 , —CH 2 N(CH 3 ) 2 , —(CH 2 ) 2 N(CH 3 ) 2 , —(CH 2 ) 2 NH(CH 2 ) 2 OH, —(CH 2 ) 3 NH(CH 2 ) 2 OH, —(CH 2 ) 2 NHCH 2 OH, —(CH 2 ) 3 NHCH 2 OH, —CH 2 CH(CH 3 ) 2 , —CHCl 2 , —CH(CH 3 )Cl, —(CH 2 ) 2 Cl, —(CH 2 ) 3 Cl, —(CH 2 ) 3 Br, —(CH 2 ) 4 Br, and —(CH 2 ) 4 Cl. Chart 1. Activation of hTERT promoter-driven SEAP expression by c-Myc. About 1×10 7 hTERT-BJ1 cells were transfected with 13.5 μg each of plasmid pSEAP or pPhTERT-SEAP and of plasmid pMT2T or pMT2T-cMyc by electroporation. After 24 h, viable cells were harvested, and reinoculated at a density of 3×10 5 /mL, and the SEAP activity after 24 h at 37 □. The transfection efficiency of each experiment was determined by cotransfection with 1.5 μg of plasmid pCMVβ. The values were determined from three experiments. P<0.05 is presented by an asterisk.

  这项发明涉及新的蒽醌化合物，可用于治疗过敏、炎症症状、抗氧化、肿瘤病情、干细胞应用、组织工程学，用于治疗与年龄相关的组织退化、慢性高周转病的器官功能衰竭以及含有这种化合物的治疗性组合物。本发明的化合物是1,4-、1,5-和1,8-二官能蒽醌或其类似物。根据本发明的实践，提供了根据式I的双对称取代蒽醌化合物：其中R1、R2、R3和R4表示直链、氨基烷基氨基侧链或具有1至6个碳的支链烷基基团，可被一个或多个R5基团取代，或者R1、R2、R3和R4表示苯基或苄基，可被一个或两个R6基团取代；其中R5选自卤素、—RNH2、—RNH2R、—ROH、—NO2、—OCH3、—OCH2CH3和—OCH2CH2CH3组成的群；其中R6选自具有1至4个碳的直链或支链烷基基团、卤素、—RNH2、—RNH2R、—ROH、—NO2、—OCH3、—OCH2CH3、—OCH2CH2CH3、—CH2Br、—CH2Cl、—CH2OH、—C(CH3)3、—(CH2)20H、—(CH2)3OH、—(CH2)4OH、—CH2NH2、—(CH2)2NH2、—(CH2)3NH2、—(CH2)4NH2、—(CH2)5NH2、—CH2N(CH3)2、—(CH2)2N(CH3)2、—(CH2)2NH(CH2)2OH、—(CH2)3NH(CH2)2OH、—(CH2)2NHCH2OH、—(CH2)3NHCH2OH、—CH2CH(CH3)2、—CHCl2、—CH(CH3)Cl、—(CH2)2Cl、—(CH2)3Cl、—(CH2)3Br、—(CH2)4Br和—(CH2)4Cl。表1. c-Myc激活hTERT启动子驱动的SEAP表达。约1×107 hTERT-BJ1细胞通过电穿孔转染了13.5 μg的pSEAP或pPhTERT-SEAP质粒和pMT2T或pMT2T-cMyc质粒。24小时后，收集活细胞，并以3×105/mL的密度重新接种，37℃下培养24小时后测定SEAP活性。每次实验的转染效率通过与1.5 μg的pCMVβ质粒共转染确定。数值是根据三次实验确定的。P<0.05由星号表示。
• US4191679A
  申请人：——

  公开号：US4191679A

  公开（公告）日：1980-03-04
• Synthesis and Antitumor Evaluation of Symmetrical 1,5-Diamidoanthraquinone Derivatives as Compared to Their Disubstituted Homologues
  作者：Hsu-Shan Huang、Hui-Fen Chiu、Chi-Wei Tao、In-Been Chen

  DOI：10.1248/cpb.54.458

  日期：——

  A series of symmetrical 1,5-diamidoanthraquinone derivatives with potentially bioreducible groups has been synthesized and their cytostatic activity against the panel of various cancer cell lines in vitro has been studied. Preliminary structure–activity relationships were established. The results indicated that compounds 5 and 18 exhibited significant potent cytotoxicity at 1.24—1.75 μM for Hepa G2 cell line; compounds 5, 16, and 18 exhibited cytotoxicity at 0.14—1.82 μM for 2.2.15 cell line as determined by XTT colorimetric assay. Two structurally related compounds, mitoxantrone and adriamycin, were tested in parallel as positive controls. In addition, it was found that compounds 5 and 18 were a more potent and specific human hepatoma cell line than mitoxantrone and showed comparable activity to adriamycin. Among them, compound 18 was the most potent for 2.2.15 cells. We have demonstrated that the anthraquinone moiety is essential for activity and that less sterically hindered substituents contribute to enhanced in vitro efficacy. Implications for amidoanthraquinone cytotoxicity as potential anticancer agents are discussed. We further delineate the nature of the pharmacophore for this class of compounds, which provides a rational basis for the structure–activity relationships.

  一系列对称的1,5-二氨基蒽醌衍生物已被合成，并研究了其对多种癌细胞系的细胞抑制活性。初步的结构-活性关系得到了建立。结果显示，化合物5和18在1.24-1.75 μM时对Hepa G2细胞系表现出显著的细胞毒性；化合物5、16和18在0.14-1.82 μM时对2.2.15细胞系表现出细胞毒性，通过XTT比色法进行了测定。两种结构相关的化合物，米托蒽醌和阿霉素，被作为阳性对照进行平行测试。此外，发现化合物5和18在对人肝癌细胞系的活性上比米托蒽醌更强，而与阿霉素的活性相当。在上述化合物中，化合物18对2.2.15细胞的活性最强。我们证明了蒽醌基团对于活性是必不可少的，且较少空间位阻的取代基有助于增强体外活性。讨论了氨基蒽醌类化合物作为潜在抗癌剂的细胞毒性影响。我们进一步阐明了这一类化合物的药效基团的性质，为结构-活性关系提供了合理依据。