7-chloro-8-hydroxymethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline | 681441-53-2

• 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: 7-chloro-8-hydroxymethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline
• 英文别名: (7-Chloro-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl)methanol
• CAS: 681441-53-2
• 化学式: C₁₂H₁₀ClNO₃
• 分子量: 251.669
• InChiKey: SZDZBIGZVLBJGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-8-hydroxymethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline 在 palladium diacetate 、 t-Bu₃Ph 、 四丁基溴化铵 、 sodium acetate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 39.0h， 生成 8-ethyl-8-hydroxy-2,3,8,9,12,15-hexahydro-10H,13H-[1,4]dioxino[2,3-g]oxepino[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione
  参考文献：
  名称：

  Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues

  摘要：

  Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell. lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

  DOI：

  10.1021/jm980400l
• 作为产物：
  描述：

  7-chloro-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carbaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.58h， 以90%的产率得到7-chloro-8-hydroxymethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline
  参考文献：
  名称：

  新型2,3-二氢-1,4-二氧杂[2,3-g]喹啉衍生物的合成作为潜在的抗肿瘤药物。

  摘要：

  已经合成了新的二恶英喹啉（1-8），并已针对几种细胞系测试了它们的抗增殖特性。在DMF存在下用三氯氧化磷处理6-乙酰氨基-2,3-二氢-1,4-苯并二恶英（10）导致线性和有角的三环化合物的混合物。对关键中间体进行了修饰和环化，得到了相应的二恶英喹啉。通常，这些化合物具有适度的柠檬酸。

  DOI：

  10.1016/j.bmc.2003.12.024

文献信息

• Synthesis of novel 2,3-dihydro-1,4-dioxino[2,3- g ]quinoline derivatives as potential antitumor agents
  作者：M.T Vázquez、M Romero、M.D Pujol

  DOI：10.1016/j.bmc.2003.12.024

  日期：2004.3

  New dioxinoquinolines (1-8) have been synthesized and their antiproliferative properties have been tested against several cell lines. The treatment of the 6-acetamido-2,3-dihydro-1,4-benzodioxine (10) with phosphorous oxychloride in the presence of DMF leads to a mixture of linear and angular tricyclic compounds. The key intermediates were modified and cyclized giving the corresponding dioxinoquinolines

  已经合成了新的二恶英喹啉（1-8），并已针对几种细胞系测试了它们的抗增殖特性。在DMF存在下用三氯氧化磷处理6-乙酰氨基-2,3-二氢-1,4-苯并二恶英（10）导致线性和有角的三环化合物的混合物。对关键中间体进行了修饰和环化，得到了相应的二恶英喹啉。通常，这些化合物具有适度的柠檬酸。
• Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues
  作者：Olivier Lavergne、Laurence Lesueur-Ginot、Francesc Pla Rodas、Philip G. Kasprzyk、Jacques Pommier、Danièle Demarquay、Grégoire Prévost、Gérard Ulibarri、Alain Rolland、Anne-Marie Schiano-Liberatore、Jeremiah Harnett、Dominique Pons、José Camara、Dennis C. H. Bigg

  DOI：10.1021/jm980400l

  日期：1998.12.1

  Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell. lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.