1,4-bis-{[2-(2-hydroxymethylpiperidin-1-yl)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione | 857637-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1,4-bis-{[2-(2-hydroxymethylpiperidin-1-yl)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione
• 英文别名: 1,4-Bis-{[2-(2-hydroxymethylpiperidine-1-yl)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione；1,4-dihydroxy-5,8-bis[2-[2-(hydroxymethyl)piperidin-1-yl]ethylamino]anthracene-9,10-dione
• CAS: 857637-13-9
• 化学式: C₃₀H₄₀N₄O₆
• 分子量: 552.671
• InChiKey: KVXMZHZWICMYGI-UHFFFAOYSA-N

物化性质

• 沸点：
  839.6±65.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  146
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1,4-bis-{[2-(2-hydroxymethylpiperidin-1-yl)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione 在 四氯化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 1,4-bis-{[2-(2-chloromethylpiperidin-1-yl)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione
  参考文献：
  名称：

  Synthesis of DNA-Directed Pyrrolidinyl and Piperidinyl Confined Alkylating Chloroalkylaminoanthraquinones:  Potential for Development of Tumor-Selective N-Oxides

  摘要：

  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.

  DOI：

  10.1021/jm0608154
• 作为产物：
  描述：

  1-(2-氨基乙基)-2-哌啶甲醇 、 1,4-二氟-5,8-二羟基蒽醌 在 吡啶 作用下， 反应 1.0h， 以34%的产率得到1,4-bis-{[2-(2-hydroxymethylpiperidin-1-yl)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione
  参考文献：
  名称：

  [EN] ANTHARQUINONE COMPOUNDS AS ANTI CANCER COMPOUNDS
  [FR] UTILISATION DE COMPOSES D'ANTHRAQUINONE EN TANT QUE COMPOSES ANTICANCEREUX

  摘要：

  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。

  公开号：

  WO2005061453A1

文献信息

• Anthraquinone compounds as anti cancer compounds
  申请人：Somanta Limited

  公开号：US07557215B2

  公开（公告）日：2009-07-07

  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）或其盐（式I）的蒽醌类化合物，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或可选取代的C1-4烷基，以及公式（II）的基团，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、芳氧基或酰氧基；X2为卤素原子、羟基、C1-6烷氧基、芳氧基或酰氧基；但要求R1至R4中至少有一个是公式（II）的基团。N-氧化物是有用的前药，可在低氧肿瘤中选择性地生物还原为相应的环状胺衍生物。胺类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在癌症治疗中使用。
• ANTHRAQUINONE COMPOUNDS AS ANTI CANCER COMPOUNDS
  申请人：Somanta Limited

  公开号：EP1701939B1

  公开（公告）日：2009-02-25
• US7557215B2
  申请人：——

  公开号：US7557215B2

  公开（公告）日：2009-07-07
• 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.
• [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。