(+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one

• 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: (+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one
• 英文别名: (5S,6S)-5,6-dihydroxy-11-methoxy-2,7,7-trimethyl-8-oxa-2-azapentacyclo[12.8.0.03,12.04,9.015,20]docosa-1(14),3,9,11,15,17,19,21-octaen-13-one
• 化学式: C₂₄H₂₃NO₅
• 分子量: 405.45
• InChiKey: CDRRPLDAWDEYGS-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 63.0h， 生成 (+/-)-cis-1-acetoxy-2-isovaleroyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one
  参考文献：
  名称：

  Synthesis, Antitumor Activity, and Mechanism of Action of Benzo[a]pyrano[3,2-h]acridin-7-one Analogues of Acronycine

  摘要：

  Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a] pyrano[3,2-h] acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA. Among the most active compounds, 25, with IC50 values of 0.7 and 0.15 mu M against L1210 and KB-3-1, respectively, was selected for evaluation in vivo against Colon 38 adenocarcinoma implanted in mice. This compound was active at 3 mg/kg iv (day 12 and 24) with 3/7 tumor free mice by day 80.

  DOI：

  10.1021/jm0602007
• 作为产物：
  描述：

  2-甲氧基-1-萘甲酸 在 四氧化锇 、 三氯化铝 、 氯化亚砜 、 氢溴酸 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 257.25h， 生成 (+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one
  参考文献：
  名称：

  Synthesis, Antitumor Activity, and Mechanism of Action of Benzo[a]pyrano[3,2-h]acridin-7-one Analogues of Acronycine

  摘要：

  Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a] pyrano[3,2-h] acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA. Among the most active compounds, 25, with IC50 values of 0.7 and 0.15 mu M against L1210 and KB-3-1, respectively, was selected for evaluation in vivo against Colon 38 adenocarcinoma implanted in mice. This compound was active at 3 mg/kg iv (day 12 and 24) with 3/7 tumor free mice by day 80.

  DOI：

  10.1021/jm0602007

文献信息

• US7276512B2
  申请人：——

  公开号：US7276512B2

  公开（公告）日：2007-10-02
• Synthesis, Antitumor Activity, and Mechanism of Action of Benzo[<i>a</i>]pyrano[3,2-<i>h</i>]acridin-7-one Analogues of Acronycine
  作者：Tuan Minh Nguyen、Chavalit Sittisombut、Sabrina Boutefnouchet、Marie-Christine Lallemand、Sylvie Michel、Michel Koch、François Tillequin、Romain Mazinghien、Amélie Lansiaux、Marie-Hélène David-Cordonnier、Bruno Pfeiffer、Laurence Kraus-Berthier、Stéphane Léonce、Alain Pierré

  DOI：10.1021/jm0602007

  日期：2006.6.1

  Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a] pyrano[3,2-h] acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA. Among the most active compounds, 25, with IC50 values of 0.7 and 0.15 mu M against L1210 and KB-3-1, respectively, was selected for evaluation in vivo against Colon 38 adenocarcinoma implanted in mice. This compound was active at 3 mg/kg iv (day 12 and 24) with 3/7 tumor free mice by day 80.