10-Hydroxy-5,5-dimethyl-6-methylidene-7-oxa-2-azapentacyclo[11.8.0.03,11.04,8.015,20]henicosa-1(21),3(11),4(8),9,13,15,17,19-octaen-12-one | 284671-57-4

• 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: 10-Hydroxy-5,5-dimethyl-6-methylidene-7-oxa-2-azapentacyclo[11.8.0.03,11.04,8.015,20]henicosa-1(21),3(11),4(8),9,13,15,17,19-octaen-12-one
• CAS: 284671-57-4
• 化学式: C₂₂H₁₇NO₃
• 分子量: 343.382
• InChiKey: AJDQXZNYJOVAHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 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：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硫酸二甲酯 、 10-Hydroxy-5,5-dimethyl-6-methylidene-7-oxa-2-azapentacyclo[11.8.0.03,11.04,8.015,20]henicosa-1(21),3(11),4(8),9,13,15,17,19-octaen-12-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以82%的产率得到10-Hydroxy-2,5,5-trimethyl-6-methylidene-7-oxa-2-azapentacyclo[11.8.0.03,11.04,8.015,20]henicosa-1(21),3(11),4(8),9,13,15,17,19-octaen-12-one
  参考文献：
  名称：

  Synthesis and Cytotoxic and Antitumor Activity of Benzo[b]pyrano[3,2-h]acridin-7-one Analogues of Acronycine

  摘要：

  Benzo[b]acronycine (6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one, 4), an acronycine analogue with an additional aromatic ring linearly fused on the natural alkaloid basic skeleton, was synthesized in three steps, starting from 3-amino-2-naphthalenecarboxylic acid (5). Eight 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine esters and diesters (17-24) were obtained by catalytic osmic oxidation, followed by acylation. All these compounds were significantly more cytotoxic than acronycine, when tested against L1210 leukemia cells in vitro. The potency of the cyclic carbonate 24 was in the range of the most active drugs currently used in cancer chemotherapy. Two selected diesters (17 and 24) were evaluated in vivo against P388 leukemia and colon 38 adenocarcinoma implanted in mice. Both compounds were markedly active at doses 16-fold lower than the dose of acronycine itself. Against colon 38 adenocarcinoma, compounds 17 and 24 were highly efficient, inhibiting tumor growth by more than 80%. Diacetate 17 was the most active, inhibiting tumor growth by 96% at 6.25 mg/kg, with two of seven mice being tumor-free on day 43.

  DOI：

  10.1021/jm990972l
• 作为产物：
  描述：

  1,3-Dihydroxy-5,12-dihydro-benzo[b]acridin-12-one 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 10-Hydroxy-5,5-dimethyl-6-methylidene-7-oxa-2-azapentacyclo[11.8.0.03,11.04,8.015,20]henicosa-1(21),3(11),4(8),9,13,15,17,19-octaen-12-one
  参考文献：
  名称：

  Synthesis and Cytotoxic and Antitumor Activity of Benzo[b]pyrano[3,2-h]acridin-7-one Analogues of Acronycine

  摘要：

  Benzo[b]acronycine (6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one, 4), an acronycine analogue with an additional aromatic ring linearly fused on the natural alkaloid basic skeleton, was synthesized in three steps, starting from 3-amino-2-naphthalenecarboxylic acid (5). Eight 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine esters and diesters (17-24) were obtained by catalytic osmic oxidation, followed by acylation. All these compounds were significantly more cytotoxic than acronycine, when tested against L1210 leukemia cells in vitro. The potency of the cyclic carbonate 24 was in the range of the most active drugs currently used in cancer chemotherapy. Two selected diesters (17 and 24) were evaluated in vivo against P388 leukemia and colon 38 adenocarcinoma implanted in mice. Both compounds were markedly active at doses 16-fold lower than the dose of acronycine itself. Against colon 38 adenocarcinoma, compounds 17 and 24 were highly efficient, inhibiting tumor growth by more than 80%. Diacetate 17 was the most active, inhibiting tumor growth by 96% at 6.25 mg/kg, with two of seven mice being tumor-free on day 43.

  DOI：

  10.1021/jm990972l

文献信息

• Synthesis and Cytotoxic and Antitumor Activity of Benzo[<i>b</i>]pyrano[3,2-<i>h</i>]acridin-7-one Analogues of Acronycine
  作者：Nadine Costes、Hervé Le Deit、Sylvie Michel、François Tillequin、Michel Koch、Bruno Pfeiffer、Pierre Renard、Stéphane Léonce、Nicolas Guilbaud、Laurence Kraus-Berthier、Alain Pierré、Ghanem Atassi

  DOI：10.1021/jm990972l

  日期：2000.6.1

  Benzo[b]acronycine (6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one, 4), an acronycine analogue with an additional aromatic ring linearly fused on the natural alkaloid basic skeleton, was synthesized in three steps, starting from 3-amino-2-naphthalenecarboxylic acid (5). Eight 1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine esters and diesters (17-24) were obtained by catalytic osmic oxidation, followed by acylation. All these compounds were significantly more cytotoxic than acronycine, when tested against L1210 leukemia cells in vitro. The potency of the cyclic carbonate 24 was in the range of the most active drugs currently used in cancer chemotherapy. Two selected diesters (17 and 24) were evaluated in vivo against P388 leukemia and colon 38 adenocarcinoma implanted in mice. Both compounds were markedly active at doses 16-fold lower than the dose of acronycine itself. Against colon 38 adenocarcinoma, compounds 17 and 24 were highly efficient, inhibiting tumor growth by more than 80%. Diacetate 17 was the most active, inhibiting tumor growth by 96% at 6.25 mg/kg, with two of seven mice being tumor-free on day 43.