1,2,7,8,9,10-hexahydro-4-<(trimethylacetyl)amino>cyclopentanoanthracene-1,2-dione | 160555-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1,2,7,8,9,10-hexahydro-4-<(trimethylacetyl)amino>cyclopentanoanthracene-1,2-dione
• 英文别名: 4-(trimethylacetyl)amino-1,2,7,8,9,10-hexahydrocyclopentano[de]anthracene-1,2-dione；8,9-oxalyl-6-trimethylacetylamino-1,2,3,4-tetrahydroanthracene；N-(1,2-dioxo-7,8,9,10-tetrahydroaceanthrylen-4-yl)-2,2-dimethylpropanamide
• CAS: 160555-13-5
• 化学式: C₂₁H₂₁NO₃
• 分子量: 335.403
• InChiKey: ARQJPTFBZUGXOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2,7,8,9,10-hexahydro-4-<(trimethylacetyl)amino>cyclopentanoanthracene-1,2-dione 在 sodium hydroxide 、 双氧水 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 3-(trimethylacetyl)aminoanthracene-1,9-dicarboxylic acid anhydride
  参考文献：
  名称：

  Analogues of Amonafide and Azonafide with Novel Ring Systems

  摘要：

  Three new types of amonafide and azonafide analogues were synthesized and screened in a panel of human solid tumor cells and murine L1210 leukemia cells. The structural types included tetrahydroazonafides, which have the naphthalene chromophore of amonafide within the anthracene nucleus of azonafide; phenanthrene analogues, in which the linear anthracene nucleus is replaced by the bent phenanthrene nucleus; and azaphenanthrenes. The tetrahydroazonafides were generally intermediate in potencies between amonafide and azonafide against the tumor cells, but some of them had high potencies against the L1210 cells and were more potent against the MDR strain than the sensitive strain. The phenanthrene and azaphenanthrene analogues showed no improvement on the potencies of the anthracenes.

  DOI：

  10.1021/jm9905817
• 作为产物：
  描述：

  草酰氯 、 6-<(trimethylacetyl)amino>-1,2,3,4-tetrahydroanthracene 在 三氯化铝 sodium hydroxide 作用下， 以 二硫化碳 、 氯仿 为溶剂， 以232 mg (4.3%)的产率得到1,2,7,8,9,10-hexahydro-3-<(trimethylacetyl)amino>cyclopentanoanthracene-1,2-dione
  参考文献：
  名称：

  1, 2-dihydro-3H-dibenzisoquinoline-1,3-dione anticancer agents

  摘要：

  这项发明涉及一种用于治疗具有以下化学式的肿瘤的化合物：##STR1##

  公开号：

  US05635506A1

文献信息

• 1, 2-dihydro-3H-dibenzisoquinoline-1,3-dione anticancer agents
  申请人：Research Corporation Technologies, Inc.

  公开号：US05635506A1

  公开（公告）日：1997-06-03

  This invention relates to a compound useful for the treatment of tumors having the formula: ##STR1##

  这项发明涉及一种用于治疗具有以下化学式的肿瘤的化合物：##STR1##
• 1,2 DIHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3 DIONE AND THEIR USE AS ANTICANCER AGENTS
  申请人：RESEARCH CORPORATION TECHNOLOGIES

  公开号：EP0660824A1

  公开（公告）日：1995-07-05
• US5635506A
  申请人：——

  公开号：US5635506A

  公开（公告）日：1997-06-03
• [EN] 1,2 DIHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3 DIONE AND THEIR USE AS ANTICANCER AGENTS<br/>[FR] 1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX
  申请人：——

  公开号：WO1994006771A1

  公开（公告）日：1994-03-31

  [EN] This invention relates to a compound useful for the treatment of tumors having formula (I), wherein R8, R6 and R10 are independently hydrogen, lower alkyl, aryl, lower alkanoyl, formyl, halogen, hydrazino, nitro, NR2R3, OR1, or SR1, methoxy, hydroxy, CO2H, SO2NR1R2, or CONR1R2; R1, R2 and R3 are independently hydrogen, lower alkyl, aryl lower alkyl, aryl, formyl or lower alkanoyl; R9, R11, R10 and R7 are independently hydrogen, or lower alkyl or R9 and R11 taken together with the carbon atoms to which they are attached form a phenyl group or R9 and R10 taken together with the carbon atoms to which they are attached form a phenyl group or R7 and R10 taken together with the carbon atoms to which they are attached form a phenyl group; A is (CR4R5)n3, lower cycloalkyl or aryl or a chemical bond; each R4 and R5 are independently hydrogen or lower alkyl; R12 and R13 are independently hydrogen, or lower alkyl which is unsubstituted or substituted with hydroxy, mercapto, lower alkoxy, lower alkylcarbonyloxy, carboxy, or carbloweralkoxy or R12 and R13 taken together with the nitrogen to which they are attached form a 3-6-membered heterocyclic ring; D is a chemical bond or taken together with NR12 forms a 5 or 6-membered heterocyclic ring; n1 and n2 are independently 0, 1 or 2; and n3 is 0, 1, 2, 3, 4 or 5.
  [FR] L'invention concerne un composé utile pour le traitement des tumeurs représenté par la formule (I) dans laquelle, R8, R6 et R10 représentent indépendamment hydrogène, alkyle inférieur, aryle, alkanoyle, formyle, halogène, hydrazino, nitro, NR2R3, OR1, ou SR1, méthoxy, hydroxy, CO2H, SO2NR1R2 ou CONR1R2; R1, R2 et R3 représentent indépendamment hydrogène, alkyle inférieur, alkyle inférieur d'aryle, aryle, formyle ou alkanoyle inférieur, R9, R11, R10 et R7 représentent indépendamment hydrogène, ou alkyle inférieur ou R9 et R11 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle ou R9 et R10 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle ou R7 et R10 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle; A représente (CR4R5)n3, cycloalkyle inférieur ou aryle ou une liaison chimique; chaque R4 et R5 représente indépendamment hydrogène ou alkyle inférieur, R12 et R13 représentent indépendamment hydrogène, ou alkyle inférieur non substitué ou substitué par hydroxy, mercapto, alcoxy ou substitué par hydroxy, mercapto, alcoxy inférieur, carbonyloxy d'aryle inférieur, carboxy ou carbo-alcoxy inférieur ou R12 et R13 considérés ensemble avec l'azote auquel ils sont attachés forment un hétérocycle à 3-6 éléments; D représente une liaison chimique ou forme lorsqu'il est considéré avec NR12 un hétérocyle à 5 ou 6 éléments; n1 et n2 représentent indépendamment 0, 1 ou 2; et n3 représente 0, 1, 2, 3, 4 ou 5.
• Amino-Substituted 2-[2-(Dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. Synthesis, Antitumor Activity, and Quantitative Structure-Activity Relationship
  作者：Salah M. Sami、Robert T. Dorr、Aniko M. Solyom、David S. Alberts、William A. Remers

  DOI：10.1021/jm00006a018

  日期：1995.3

  Sets of 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with amino and actylamino groups at each of the eight positions on the anthracene nucleus were synthesized from appropriately substituted anthracenes. Their evaluation in in vitro antitumor and cardiotoxicity assays revealed a very strong dependence of potency on the position of substitution. Certain compounds, including the 4-, 5-, 7-, and 9-amino derivatives, showed significantly higher potency than the unsubstituted parent compound, azonafide. Among them, 7-aminoazonafide had low cardiotoxicity relative to cytotoxicity. In general, the acetylamino analogues were less potent than the amino derivatives against tumor cells and neonatal rat heart myocytes; however, 5-(acetylamino)azonafide was highly cardiotoxic. 9-Aminoazonafide was more efficacious than azonafide or amonafide against P388 leukemia in mice. Statistically significant correlations were made between the ability of amino analogues to increase the transition melt temperature (Delta T-m) of DNA and their potency against solid tumors, leukemia cells, or cardiac myocytes.