9,11-dihydroxybenzo[a]acridin-12(7H)-one | 818375-07-4

• 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: 9,11-dihydroxybenzo[a]acridin-12(7H)-one
• 英文别名: 9,11-dihydroxybenzo[α]acridin-12(7H)-one；9,11-Di-hydroxybenzo [a]acridin-12(7h)-one；9,11-dihydroxy-7H-benzo[a]acridin-12-one
• CAS: 818375-07-4
• 化学式: C₁₇H₁₁NO₃
• 分子量: 277.279
• InChiKey: YZCFEHNEXQQNFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9,11-dihydroxybenzo[a]acridin-12(7H)-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 27.25h， 生成 6-hydroxy-3,3-dimethyl-3,14-dihydro-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 三氯化铝 、 氯化亚砜 、 氢溴酸 、 sodium hydride 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 129.5h， 生成 9,11-dihydroxybenzo[a]acridin-12(7H)-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

• Benzo[a]pyrano[3,2-h]acridin-7-one compounds
  申请人：——

  公开号：US20040266753A1

  公开（公告）日：2004-12-30

  A compound selected from those of formula (I): 1 wherein: X and Y represent a group selected from hydrogen, halogen, hydroxy, alkoxy, nitro, cyano, alkyl, trihaloalkyl and NR a R b , wherein R a and R b are as defined in the description R 1 represents hydrogen or alkyl R 2 represents a group selected from hydrogen, alkyl, —OR″ a , —NR′ a R′ b , -T a -O″ a , —N″ a -T a -NR′ a R′ b , —N″ a —C(O)-T a H, —O—C(O) T a H, T a -NR′ a R′ b , —NR″ a -T a -OR″ a , —NR″ a -T a -CO 2 R″ a and —N″ a —C(O)-T a -NR′ a R′ b , wherein R′ a , R″ a , R′b and T a are as defined in the description R 3 and R 4 represent hydrogen or alkyl A represents a group of formula —CH(R 5 )CH(R 6 ), —CH═C(R 7 )—, —C(R 7 )═CH—, —C(O)CH(R 8 ) or —CH(R 8 )—C(O), wherein R 5 , R 6 , R 7 and R 8 are as defined in the description its isomers, N-oxides, and addition salts thereof with a pharmaceutically acceptable acid or base, and medicinal products containing the same which are useful in the treatment of cancer.

  从以下公式（I）中选择的一种化合物：其中：X和Y代表从氢、卤素、羟基、烷氧基、硝基、氰基、烷基、三卤代烷基和NRaRb中选择的基团，其中Ra和Rb如描述中所定义；R1代表氢或烷基；R2代表从氢、烷基、—OR″a、—NR′aR′b、-Ta-O″a、—N″a-Ta-NR′aR′b、—N″a—C(O)-TaH、—O—C(O) TaH、Ta-NR′aR′b、—NR″a-Ta-OR″a、—NR″a-Ta-CO2R″a和—N″a—C(O)-Ta-NR′aR′b中选择的基团，其中R′a、R″a、R′b和Ta如描述中所定义；R3和R4代表氢或烷基；A代表公式—CH(R5)CH(R6)、—CH═C(R7)—、—C(R7)═CH—、—C(O)CH(R8)或—CH(R8)—C(O)中选择的基团，其中R5、R6、R7和R8如描述中所定义的其异构体、N-氧化物以及与药学上可接受的酸或碱形成的加合盐，以及含有这种化合物的药物产品，适用于癌症治疗。
• 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.