tert-butyl 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolixino<1,2-b>quinolin-2-yl)pentanoate | 186668-38-2

• 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: tert-butyl 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolixino<1,2-b>quinolin-2-yl)pentanoate
• 英文别名: tert-butyl 3-hydroxy-3-[8-(hydroxymethyl)-9-oxo-9,11-dihydroindolizino[1,2-b]quinolin-7-yl]pentanoate；tert-butyl 3-hydroxy-3-[8-(hydroxymethyl)-9-oxo-11H-indolizino[1,2-b]quinolin-7-yl]pentanoate
• CAS: 186668-38-2
• 化学式: C₂₅H₂₈N₂O₅
• 分子量: 436.508
• InChiKey: ZPPNZZMGZJVRMV-UHFFFAOYSA-N

物化性质

• 沸点：
  716.0±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolixino<1,2-b>quinolin-2-yl)pentanoate 在 盐酸 、 氢氧化钾 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolizino<1,2-b>quinolin-2-yl)pentanoic acid
  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：

  喜树碱 在 sodium tetrahydroborate 、 sodium periodate 、 三甲基氯硅烷 、 氮 、 锌 作用下， 以 甲醇 为溶剂， 生成 tert-butyl 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolixino<1,2-b>quinolin-2-yl)pentanoate
  参考文献：
  名称：

  新型20-O-连接的喜树碱酯衍生物作为强效拓扑异构酶I抑制剂的合成和细胞毒性。

  摘要：

  为了改善高喜树碱（hCPT）的抗肿瘤活性，首先基于合成路线设计和合成了一系列新颖的20- O-连接的hCPT酯衍生物，通过该合成路线，hCPT被不同的取代的苯氧基乙酸酯衍生物酰化。对大多数衍生物进行了针对六种人类癌细胞系KB，KB / VCR，A549，HCT-8，Bel7402和A2780的体外细胞毒性测定，并且大多数测定的化合物对这些肿瘤细胞系表现出良好的抗增殖活性，尤其是对KB

  DOI：

  10.1080/10286020.2013.855203

文献信息

• E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation
  作者：Giuseppe Giannini、Mauro Marzi、Walter Cabri、Elena Marastoni、Gianfranco Battistuzzi、Loredana Vesci、Claudio Pisano、Giovanni Luca Beretta、Michelandrea De Cesare、Franco Zunino

  DOI：10.1016/j.bmcl.2008.03.074

  日期：2008.5

  derivatives of homocamptothecins showed ability to form stable ternary complexes with DNA and topoisomerase I. The 7-oxyiminomethyl derivatives of homocamptothecins were evaluated as a racemic mixture. Following the isolation of the two enantiomers, the 20 (R)-hydroxy isomer confirms the best activity. By using a panel of human tumor cells, all tested homocamptothecins showed a potent antiproliferative activity

  与五元E环类似物相反，高喜树碱的7-氧亚氨基甲基衍生物具有与DNA和拓扑异构酶I形成稳定的三元复合物的能力。高喜树碱的7-氧亚氨基甲基衍生物被评估为外消旋混合物。在分离出两种对映异构体之后，20（R）-羟基异构体证实了最佳活性。通过使用一组人类肿瘤细胞，所有测试的同型喜树碱均显示出有效的抗增殖活性，与可裂解复合物的持久性相关。在天然支架和相应的喜树碱同系物之间没有观察到显着差异。该系列的选定化合物对人胃肠道肿瘤异种移植物表现出优异的抗肿瘤活性。
• Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06339091B1

  公开（公告）日：2002-01-15

  The compound of the formula wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.

  该化合物的结构如下所示，其中取代基的定义如规范中所述，以及其无毒、药用可接受的盐，可用于治疗病毒感染、寄生虫病和癌症的治疗。
• New analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them
  申请人：——

  公开号：US20030004150A1

  公开（公告）日：2003-01-02

  A compound of the formula 1 wherein the substituents are defined as in the specification which compounds are useful in the treatment of cancer.

  其中取代基如规范中所定义的化合物的化学式，这些化合物在癌症治疗中很有用。
• Analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them
  申请人：Societe de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06815546B2

  公开（公告）日：2004-11-09

  A compound of the formula wherein the substituents are defined as in the specification which compounds are useful in the treatment of cancer.

  该化合物的化学式，其中取代基的定义如规范中所述，这些化合物在癌症治疗中很有用。
• BN 80245: An E-ring modified camptothecin with potent antiproliferative and topoisomerase I inhibitory activities
  作者：Olivier Lavergne、Laurence Lesueur-Ginot、Francesc Pla Rodas、Dennis C.H. Bigg

  DOI：10.1016/s0960-894x(97)00398-3

  日期：1997.9

  The crucial E-ring of camptothecin has been modified to afford the homologous beta-hydroxylactone derivative BN 80245. This compound, which is more stable than camptothecin, remains a potent inhibitor of both cell growth and topoisomerase I. (C) 1997 Elsevier Science Ltd.