10-methoxycamptothecin-7-aldehyde | 308085-52-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 10-methoxycamptothecin-7-aldehyde
• 英文别名: (19S)-19-ethyl-19-hydroxy-7-methoxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-10-carbaldehyde
• CAS: 308085-52-1
• 化学式: C₂₂H₁₈N₂O₆
• 分子量: 406.395
• InChiKey: FQJGWKURACUHSX-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  10-methoxycamptothecin-7-aldehyde 在 甲酸 、 盐酸羟胺 、 sodium formate 作用下， 反应 4.0h， 以35%的产率得到(19S)-19-ethyl-19-hydroxy-7-methoxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-10-carbonitrile
  参考文献：
  名称：

  Novel 7-Substituted Camptothecins with Potent Antitumor Activity

  摘要：

  The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC50 values in the 0.05-1 muM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.

  DOI：

  10.1021/jm000944z
• 作为产物：
  描述：

  9-甲氧基喜树碱 在 硫酸 、 双氧水 、 iron(II) sulfate 作用下， 反应 101.0h， 生成 10-methoxycamptothecin-7-aldehyde
  参考文献：
  名称：

  Novel 7-Substituted Camptothecins with Potent Antitumor Activity

  摘要：

  The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC50 values in the 0.05-1 muM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.

  DOI：

  10.1021/jm000944z

文献信息

• Novel 7-Oxyiminomethyl Derivatives of Camptothecin with Potent in Vitro and in Vivo Antitumor Activity
  作者：Sabrina Dallavalle、Anna Ferrari、Barbara Biasotti、Lucio Merlini、Sergio Penco、Grazia Gallo、Mauro Marzi、Maria Ornella Tinti、Roberta Martinelli、Claudio Pisano、Paolo Carminati、Nives Carenini、Giovanni Beretta、Paola Perego、Michelandrea De Cesare、Graziella Pratesi、Franco Zunino

  DOI：10.1021/jm0108092

  日期：2001.9.1

  In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for

  为了合成可能通过抑制拓扑异构酶I（Topo I）起作用的潜在抗癌药，制备了喜树碱（CPT）7位上的一系列新的氧亚氨基甲基衍生物。合成依赖于20S-CPT-7-醛或20S-CPT-7-酮与烷基，芳基，杂芳基，芳基烷基和杂芳基烷基O取代的羟胺的缩合。测试了这些化合物在体外对H460非小肺癌细胞系的细胞毒性活性，该活性针对0.01-0.3 microM范围内的37种化合物中的24种。QSAR分析表明，亲脂性是与细胞毒性相关的主要参数。对DNA-Topo I-药物可裂解复合物的研究表明，细胞毒性与Topo I抑制之间存在大致平行的关系。NaCl介导的三元复合物破坏后DNA裂解的持续性表明，对于最有效的化合物（例如15），细胞毒性至少部分与复合物的稳定有关，这也得到了DNA-的持续性的支持。药物处理细胞中的酶复合物。使用人肺肿瘤异种移植模型，与托泊替康直接比较，评估了最有效类似物（15）的体内抗肿瘤功效。在最佳剂量（2-3
• [EN] TREATMENT OF HYPERPROLIFERATIVE DISEASES WITH CAMPTOTHECINE N-OXIDE AND ANALOGS<br/>[FR] traitement de maladies hyperprolifEratives avec la camptothecine n-oxyde et des analogues de celle-ci
  申请人：NOVACEA INC

  公开号：WO2007095389A2

  公开（公告）日：2007-08-23

  [EN] The invention relates to N-oxides of camptothecin analogs having activity for treating hyperproliferative disorders. Pharmaceutical compositions comprising therapeutically effective amount of camptothecin analog N-oxides and bis N-oxides, or a pharmaceutically acceptable salt or prodrug thereof, are disclosed. Further, the invention relates to methods of using the compounds, alone or in combination with one or more other active agents or treatments, to treat hyperproliferative disorders.
  [FR] L'invention concerne des N-oxydes d'analogues de camptothécine ayant une activité pour le traitement de maladies hyperprolifératives. Des compositions pharmaceutiques comprenant une quantité efficace d'un point de vue thérapeutique de N-oxydes et de N-oxydes bis d'analogues de camptothécine, ou des sels ou un promédicament de ceux-ci acceptables d'un point de vue pharmaceutique sont décrits. En outre, l'invention concerne des procédés d'utilisation des composés, seuls ou en association avec un ou plusieurs autres agents actifs ou traitements, pour traiter des troubles hyperprolifératifs.
• Novel 7-Substituted Camptothecins with Potent Antitumor Activity
  作者：Sabrina Dallavalle、Tatiana Delsoldato、Anna Ferrari、Lucio Merlini、Sergio Penco、Nives Carenini、Paola Perego、Michelandrea De Cesare、Graziella Pratesi、Franco Zunino

  DOI：10.1021/jm000944z

  日期：2000.10.1

  The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC50 values in the 0.05-1 muM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.