1-<<2-(dimethylamino)ethyl>amino>-4-fluoro-5,8-dihydroxyanthracene-9,10-dione | 134529-37-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1-<<2-(dimethylamino)ethyl>amino>-4-fluoro-5,8-dihydroxyanthracene-9,10-dione
• 英文别名: 1-(2-(dimethylamino)ethylamino)-4-fluoro-5,8-dihydroxyanthracene-9,10-dione；1-[2-(dimethylamino)ethylamino]-4-fluoro-5,8-dihydroxyanthracene-9,10-dione；1-[[2-(dimethylamino)ethyl]amino]-4-fluoro-5,8-dihydroxyanthracene-9,10-dione
• CAS: 134529-37-6
• 化学式: C₁₈H₁₇FN₂O₄
• 分子量: 344.342
• InChiKey: PXFUCKLHWOVIRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-<<2-(dimethylamino)ethyl>amino>-4-fluoro-5,8-dihydroxyanthracene-9,10-dione 在 吡啶 、 四氯化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 1-[2-(dimethylamino)ethylamino]-4-[2-(3-chloromethylpiperidin-1-yl)ethylamino]-5,8-dihydroxyanthracene-9,10-dione
  参考文献：
  名称：

  Development of Nonsymmetrical 1,4-Disubstituted Anthraquinones That Are Potently Active against Cisplatin-Resistant Ovarian Cancer Cells

  摘要：

  A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.

  DOI：

  10.1021/jm050438f
• 作为产物：
  描述：

  1,4-二氟-5,8-二羟基蒽醌 、 N,N-二甲基乙二胺 以 吡啶 为溶剂， 反应 28.0h， 以42%的产率得到1-<<2-(dimethylamino)ethyl>amino>-4-fluoro-5,8-dihydroxyanthracene-9,10-dione
  参考文献：
  名称：

  对称和不对称取代的1,4-双[（氨基烷基）氨基]蒽-9,10-二酮和1,4-双[（氨基烷基）氨基] -5,8-二羟基蒽-9,10-的合成及抗肿瘤评价diones。

  摘要：

  1,4-二氟蒽-9,10-二酮（3）和1,4-二氟-5,8-二羟基蒽-9,10-二酮（4）的过量二胺（或a）氟化物的ipso bis置换在室温下，在吡啶中分别得到对称的1，4-双取代的类似物5和6。可以通过用小于1摩尔当量的二胺（或单胺）处理分别产生7和8来实现氟化物从3和4的ipso单取代。用不同的二胺处理7或8分别导致不对称取代的1,4-双[（氨基烷基）氨基]蒽9,10-二酮9和10。已经评估了许多合成的不对称类似物在体外和体内对L1210的抗肿瘤活性。评价了类似物10a与米托蒽醌（2）和阿霉素的交叉抗性，体外针对MDR株抗人结肠癌LOVO及其对DOXO的亚株（LOVO / DOXO）的交叉抗性。提出和讨论了观察到的细胞毒性的潜在机制。

  DOI：

  10.1021/jm00112a009

文献信息

• [EN] ANTHARQUINONE COMPOUNDS AS ANTI CANCER COMPOUNDS<br/>[FR] UTILISATION DE COMPOSES D'ANTHRAQUINONE EN TANT QUE COMPOSES ANTICANCEREUX
  申请人：UNIV LONDON PHARMACY

  公开号：WO2005061453A1

  公开（公告）日：2005-07-07

  Anthraquinone compounds of the general formula (I) or a salt thereof (Formula I) in which R1 to R4 are each selected from the group consisting of H, C1-4 alkyl, X1, -NHR0N (R5)2 in which R0 is a C1-12 alkanediyl and each R5 is H or optionally substituted C1-4 alkyl, and a group of formula (II) in which at least one of R6,R7 and R8 is selected from X2 , and X2 substituted C1-4 alkyl and any others are H or C1-4 alkyl; R9 is selected from H, C1-4 alkyl, X2 and X2 substituted C1-4 alkyl; m is 0 or 1; n is 1 or 2; X1 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; and X2 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; provided that at least one of R1 to R4 is a group of formula (II). The N-oxides are useful prodrugs which are selectively bioreduced in hypoxic tumours to the corresponding cyclic amine derivatives. The amine compounds are cytotoxic and may be used as alkylating agents having topoisomerase II inhibiting activities in cancer therapy.

  通式（I）的蒽醌化合物或其盐（公式I），其中R1至R4分别选自H、C1-4烷基、X1、-NHR0N（R5）2，其中R0为C1-12烷二基，每个R5为H或可选择性取代的C1-4烷基，以及公式（II）中的一组，其中R6、R7和R8中至少有一个选自X2，和X2取代的C1-4烷基，其他为H或C1-4烷基；R9选自H、C1-4烷基、X2和X2取代的C1-4烷基；m为0或1；n为1或2；X1为卤素原子、羟基、C1-6烷氧基、芳基氧基或酰氧基；X2为卤素原子、羟基、C1-6烷氧基、芳基氧基或酰氧基；前提是R1至R4中至少有一个是公式（II）的一组。N-氧化物是有用的前药，可选择性地在低氧肿瘤中生物还原为相应的环胺衍生物。胺化合物具有细胞毒性，可用作在癌症治疗中具有拓扑异构酶II抑制活性的烷基化剂。
• [EN] ACETALANTHRAQUINONE DERIVATIVES USEFUL FOR CELLULAR STAINING<br/>[FR] DÉRIVÉS D'ACÉTOANTHRAQUINONE UTILISÉS POUR LA COLORATION CELLULAIRE
  申请人：BIOSTATUS LTD

  公开号：WO2017220969A1

  公开（公告）日：2017-12-28

  The present invention provides di-substituted acetalanthraquinone- based compounds of the Formulae (l)-(IV) that are useful for cellular staining and for light-based detection of biological material, e.g. fluorescence-based detection of biological material. These compounds may be used in hydrolysed or non-hydrolysed form. Also provided is a fluorescent complex that comprises a nucleic acid and an acetalanthraquinone-based compound of the invention; and a method of staining a biological sample comprising cells or other biological material containing nucleic acid, which method comprises contacting the biological sample with an acetalanthraquinone-based compound of the invention. In the Formulae (l)-(IV), A and B are each independently of formula -RaCH2CH(ORb)2; or one of A and B is of formula -RaCH2CH(ORb)2 and the other one is of formula: -NRb2.

  本发明提供了一种基于二取代乙缩醛蒽醌的化合物，其化学式为（I）-（IV），这些化合物可用于细胞染色和生物材料的光检测，例如基于荧光的生物材料检测。这些化合物可以以水解或非水解形式使用。还提供了一种包含核酸和本发明的乙缩醛蒽醌化合物的荧光复合物；以及一种染色生物样本的方法，该生物样本包含细胞或其他含有核酸的生物材料，该方法包括将生物样本与本发明的乙缩醛蒽醌化合物接触。在化学式（I）-（IV）中，A和B分别独立于式-RaCH2CH(ORb)2；或A和B中的一个为式-RaCH2CH(ORb)2，另一个为式-NRb2。
• Antharquinone Compounds as Anti Cancer Compounds
  申请人：Patterson Laurence Hylton

  公开号：US20080027107A1

  公开（公告）日：2008-01-31

  Anthraquinone compounds of the general formula (I) or a salt thereof (Formula I) in which R 1 to R 4 are each selected from the group consisting of H, C 1-4 alkyl, X 1 , —NHR 0 N (Rs)2 in which R° is a C 1 l 12 alkanediyl and each R 5 is H or optionally substituted C 14 alkyl, and a group of formula (11) in which at least one of R 6 ,R 7 and R 8 is selected from X 2 , and X 2 substituted C 1-4 alkyl and any others are H or C 14 alkyl; R 9 is selected from H, C 1 4 alkyl, X 2 and X 2 substituted C 1-4 alkyl; m is 0 or 1; n is 1 or 2; X 1 is a halogen atom, a hydroxyl group, a C 1 . 6 alkoxyl group, an aryloxy group or an acyloxy group; and X 2 is a halogen atom, a hydroxyl group, a C 1 6 alkoxyl group, an aryloxy group or an acyloxy group; provided that at least one of R 1 to R 4 is a group of formula (II). The N-oxides are useful prodrugs which are selectively bioreduced in hypoxic tumours to the corresponding cyclic amine derivatives. The amine compounds are cytotoxic and may be used as alkylating agents having topoisomerase II inhibiting activities in cancer therapy.

  通式（I）或其盐（式I）的蒽醌化合物，其中R1至R4均选自H、C1-4烷基、X1、-NHR0N（Rs）2的群，其中R°是C1l12烷二基，每个R5是H或可选取代的C14烷基，以及式（II）的一组，其中至少有一个R6、R7和R8选自X2和X2取代的C1-4烷基，其余为H或C14烷基；R9选自H、C14烷基、X2和X2取代的C1-4烷基；m为0或1；n为1或2；X1为卤素原子、羟基、C1.6烷氧基、芳基氧基或酰氧基；X2为卤素原子、羟基、C16烷氧基、芳基氧基或酰氧基；前提是至少有一个R1至R4是式（II）的一组。N-氧化物是有用的前药，在低氧肿瘤中选择性地生物还原为相应的环状胺衍生物。胺化合物具有细胞毒性，并可用作具有拓扑异构酶II抑制活性的烷基化剂，用于癌症治疗。
• Acetalanthraquinone derivatives useful for cellular staining
  申请人：BIOSTATUS LIMITED

  公开号：US11447638B2

  公开（公告）日：2022-09-20

  The present invention provides di-substituted acetalanthraquinone-based compounds of the Formulae (l)-(IV) that are useful for cellular staining and for light-based detection of biological material, e.g. fluorescence-based detection of biological material. These compounds may be used in hydrolysed or non-hydrolysed form. Also provided is a fluorescent complex that comprises a nucleic acid and an acetalanthraquinone-based compound of the invention; and a method of staining a biological sample comprising cells or other biological material containing nucleic acid, which method comprises contacting the biological sample with an acetalanthraquinone-based compound of the invention. In the Formulae (l)-(IV), A and B are each independently of formula —RaCH2CH(ORb)2; or one of A and B is of formula —RaCH2CH(ORb)2 and the other one is of formula: —NRb2.

  本发明提供了式(l)-(IV)的二取代乙酰蒽醌基化合物，可用于细胞染色和生物材料的光基检测，如生物材料的荧光检测。这些化合物可以水解或非水解形式使用。还提供了一种荧光复合物，该复合物包括核酸和本发明的乙酰蒽醌基化合物；以及一种染色生物样品的方法，该生物样品包括含有核酸的细胞或其他生物材料，该方法包括将生物样品与本发明的乙酰蒽醌基化合物接触。在式(l)-(IV)中，A和B各自独立地为式-RaCH2CH(ORb)2；或A和B中的一个为式-RaCH2CH(ORb)2，另一个为式：-NRb2。
• Synthesis of DNA-Directed Pyrrolidinyl and Piperidinyl Confined Alkylating Chloroalkylaminoanthraquinones:  Potential for Development of Tumor-Selective <i>N</i>-Oxides
  作者：Klaus Pors、Steven D. Shnyder、Paul H. Teesdale-Spittle、John A. Hartley、Mire Zloh、Mark Searcey、Laurence H. Patterson

  DOI：10.1021/jm0608154

  日期：2006.11.30

  A novel series of 1,4-disubstituted chloroethylaminoanthraquinones, containing alkylating chloroethylamino functionalities as part of a rigid piperidinyl or pyrrolidinyl ring-system, have been prepared. The target compounds were prepared by ipso-displacement of halides of various anthraquinone chromophores by either hydroxylated or chlorinated piperidinyl- or pyrrolidinyl-alkylamino side chains. The chloroethylaminoanthraquinones were shown to alkylate guanine residues of linearized pBR322 (1-20 mu M), and two symmetrically 1,4-disubstituted anthraquinones (compounds 14 and 15) were shown to interstrand cross-link DNA in the low nM range. Several 1,4-disubstituted chloroethylaminoanthraquinones were potently cytotoxic (IC(50) values: <= 40 nM) in human ovarian cancer A2780 cells. Two agents (compounds 18 and 19) exhibited mean GI(50) values of 96 nM and 182 nM, respectively, in the NCI human tumor cell line panel. Derivatization of the potent DNA cross-linking agent 15 to an N-oxide resulted in loss of the DNA unwinding, DNA interstrand cross-linking and cytotoxic activity of the parent molecule.