3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one | 570375-80-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one
• 英文别名: 7,7-Dimethyl-8-oxa-2-azapentacyclo[12.8.0.03,12.04,9.016,21]docosa-1(22),3(12),4(9),5,10,14,16,18,20-nonaen-13-one
• CAS: 570375-80-3
• 化学式: C₂₂H₁₇NO₂
• 分子量: 327.382
• InChiKey: HKMPUZJNWWRJMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one 在 吡啶 、 4-二甲氨基吡啶 、 四氧化锇 、 sodium hydride 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 99.0h， 生成 Acetic acid (1S,2S)-2-acetoxy-3,3,14-trimethyl-7-oxo-2,3,7,14-tetrahydro-1H-4-oxa-14-aza-benzo[a]naphthacen-1-yl ester
  参考文献：
  名称：

  Structure−Activity Relationships and Mechanism of Action of Antitumor Benzo[b]pyrano[3,2-h]acridin-7-one Acronycine Analogues

  摘要：

  The cytotoxic and antitumor activities of cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 3, 6-9 were strongly correlated with their ability to give covalent adducts with purified, as well as genomic, DNA. Such adducts involve reaction between the exocyclic N-2 amino group of guanines exposed in the minor groove of double helical DNA and the leaving ester group at the benzylic position 1 of the drug. A transesterification process of the ester group from position 2 to position 1 in aqueous medium accounted for the intense activity of the cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 10-13. Compounds without acyloxy or hydroxy group at position 1, such as 15, 17, 18, and 22, were inert with respect to DNA and almost devoid of significant cytotoxic activity. Condensation of 5-amino-2,2-dimethyl-2H-chromene (26) with 3-bromo-2-naphthoic acid (27), followed by cyclization, gave access to 6-demethoxy analogues. Diacetate 32 and cyclic carbonate 33, both belonging to the latter series, were less reactive toward DNA and less cytotoxic than their 6-methoxy counterparts 3 and 34. DNA alkylation appears thus to play an important role in the antitumor properties of benzo[b]pyrano[3,2-h]acridin-7-one derivatives.

  DOI：

  10.1021/jm030790y
• 作为产物：
  描述：

  3-溴萘-2-羧酸 在 potassium acetate 、 copper diacetate 、 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 71.0h， 生成 3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one
  参考文献：
  名称：

  Structure−Activity Relationships and Mechanism of Action of Antitumor Benzo[b]pyrano[3,2-h]acridin-7-one Acronycine Analogues

  摘要：

  The cytotoxic and antitumor activities of cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 3, 6-9 were strongly correlated with their ability to give covalent adducts with purified, as well as genomic, DNA. Such adducts involve reaction between the exocyclic N-2 amino group of guanines exposed in the minor groove of double helical DNA and the leaving ester group at the benzylic position 1 of the drug. A transesterification process of the ester group from position 2 to position 1 in aqueous medium accounted for the intense activity of the cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 10-13. Compounds without acyloxy or hydroxy group at position 1, such as 15, 17, 18, and 22, were inert with respect to DNA and almost devoid of significant cytotoxic activity. Condensation of 5-amino-2,2-dimethyl-2H-chromene (26) with 3-bromo-2-naphthoic acid (27), followed by cyclization, gave access to 6-demethoxy analogues. Diacetate 32 and cyclic carbonate 33, both belonging to the latter series, were less reactive toward DNA and less cytotoxic than their 6-methoxy counterparts 3 and 34. DNA alkylation appears thus to play an important role in the antitumor properties of benzo[b]pyrano[3,2-h]acridin-7-one derivatives.

  DOI：

  10.1021/jm030790y

文献信息

• Structure−Activity Relationships and Mechanism of Action of Antitumor Benzo[<i>b</i>]pyrano[3,2-<i>h</i>]acridin-7-one Acronycine Analogues
  作者：Huong Doan Thi Mai、Thomas Gaslonde、Sylvie Michel、François Tillequin、Michel Koch、Jean-Bernard Bongui、Abdelhakim Elomri、Elisabeth Seguin、Bruno Pfeiffer、Pierre Renard、Marie-Hélène David-Cordonnier、William Laine、Christian Bailly、Laurence Kraus-Berthier、Stéphane Léonce、John A. Hickman、Alain Pierré

  DOI：10.1021/jm030790y

  日期：2003.7.1

  The cytotoxic and antitumor activities of cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 3, 6-9 were strongly correlated with their ability to give covalent adducts with purified, as well as genomic, DNA. Such adducts involve reaction between the exocyclic N-2 amino group of guanines exposed in the minor groove of double helical DNA and the leaving ester group at the benzylic position 1 of the drug. A transesterification process of the ester group from position 2 to position 1 in aqueous medium accounted for the intense activity of the cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 10-13. Compounds without acyloxy or hydroxy group at position 1, such as 15, 17, 18, and 22, were inert with respect to DNA and almost devoid of significant cytotoxic activity. Condensation of 5-amino-2,2-dimethyl-2H-chromene (26) with 3-bromo-2-naphthoic acid (27), followed by cyclization, gave access to 6-demethoxy analogues. Diacetate 32 and cyclic carbonate 33, both belonging to the latter series, were less reactive toward DNA and less cytotoxic than their 6-methoxy counterparts 3 and 34. DNA alkylation appears thus to play an important role in the antitumor properties of benzo[b]pyrano[3,2-h]acridin-7-one derivatives.