10-[(2,4-dinitrophenyl)hydrazono]-1,8-dihydroxy-10H-anthracen-9-one | 156383-28-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 10-[(2,4-dinitrophenyl)hydrazono]-1,8-dihydroxy-10H-anthracen-9-one
• 英文别名: 10-[(2,4-dinitrophenyl)hydrazinylidene]-1,8-dihydroxyanthracen-9-one
• CAS: 156383-28-7
• 化学式: C₂₀H₁₂N₄O₇
• 分子量: 420.338
• InChiKey: MLCYGRKUWZFKIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  168.2
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  10-[(2,4-dinitrophenyl)hydrazono]-1,8-dihydroxy-10H-anthracen-9-one 在 acetobromo-a-D-glucose 、 三氟甲磺酸三甲基硅酯 、 sodium acetate 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 10-[(2,4-dinitrophenyl)hydrazono]-1-acetoxy-8-hydroxy-10H-anthracen-9-one
  参考文献：
  名称：

  Design, Synthesis, and Anticancer Properties of 4,4‘-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone and Analogues

  摘要：

  4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 10(2)-10(3) when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.

  DOI：

  10.1021/jm0301080
• 作为产物：
  描述：

  1,8-二羟基蒽醌 、 2,4-二硝基苯肼 在 硫酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以90%的产率得到10-[(2,4-dinitrophenyl)hydrazono]-1,8-dihydroxy-10H-anthracen-9-one
  参考文献：
  名称：

  Design, Synthesis, and Anticancer Properties of 4,4‘-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone and Analogues

  摘要：

  4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 10(2)-10(3) when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.

  DOI：

  10.1021/jm0301080

文献信息

• [EN] CYTOTOXIC COMPOUNDS<br/>[FR] COMPOSES CYTOTOXIQUES
  申请人：MORGAN, Lee, Roy

  公开号：WO1994005276A1

  公开（公告）日：1994-03-17

  (EN) Compounds are disclosed which display cytotoxic effects against estrogen-independent tumors. These compounds may be represented by the formula X-R1 wherein X is a phenyl ring which may be substituted with one or more nitro, methyl or trihalomethyl groups and R1 is a benzophenone hydrazone, a xanthone hydrazone, a thioxanthone hydrazone, a fluoren hydrazone, an anthraquinone hydrazone, an anthraquinone phenylhydrazone, an indano [1,2,3-$i(de)]-2$i(H)-phtalazinone, a tetralin [1,2,3-$i(de)]-2$i(H)-phtalazinone, an acridone hydrazone, or a dibenzosuberenone hydrazone. The R1 moiety may be substituted with one or more hydroxy, methoxy or halogen groups. These compounds are useful as chemotherapeutic antineoplastic agents.(FR) Composés présentant des effets cytotoxiques contre des tumeurs indépendantes de l'÷strogène. Ces composés peuvent être représentés par la formule X-R1 dans laquelle X représente un cycle phényle pouvant être substitué par un ou plusieurs groupes nitro, méthyle ou trihalométhyle, et R1 représente une hydrazone de benzophénone, une hydraxone de xanthone, une hydrazone de thioxanthone, une hydrazone de fluorène, une hydrazone d'anthraquinone, une phénylhydrazone d'anthraquinone, une indano [1,2,3-$i(de)]-2$i(H)-phtalazinone, une tétraline [1,2,3-$i(de)]-2$i(H)-phtalazinone, une hydrazone d'acridone, ou une hydrazone de dibenzosubérénone. La fraction R1 peut être substituée par un ou plusieurs groupes hydroxy, méthoxy ou halogène. Ces composés sont utiles en tant qu'agents chimiothérapeutiques antinéoplasiques.
• Design, Synthesis, and Anticancer Properties of 4,4‘-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone and Analogues
  作者：Lee Roy Morgan、Kanappan Thangaraj、Blaise LeBlanc、Andrew Rodgers、Lionel T. Wolford、Catherine L. Hooper、Dominic Fan、Branko S. Jursic

  DOI：10.1021/jm0301080

  日期：2003.10.1

  4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 10(2)-10(3) when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.