10-hydroxy-7-formylcamptothecin | 308085-51-0

• 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-hydroxy-7-formylcamptothecin
• 英文别名: (19S)-19-ethyl-7,19-dihydroxy-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: 308085-51-0
• 化学式: C₂₁H₁₆N₂O₆
• 分子量: 392.368
• InChiKey: ZYIWSASNWMIJFL-NRFANRHFSA-N

物化性质

• 沸点：
  879.9±65.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  10-hydroxy-7-formylcamptothecin 在 甲酸 、 盐酸羟胺 、 sodium formate 作用下， 反应 4.0h， 以79%的产率得到(19S)-19-ethyl-7,19-dihydroxy-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：

  10-羟基喜树碱 在 硫酸 、 双氧水 、 iron(II) sulfate 作用下， 反应 101.0h， 生成 10-hydroxy-7-formylcamptothecin
  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

• 具有抗肿瘤活性的喜树碱衍生物
  申请人：苏州汉德景曦新药研发有限公司

  公开号：CN103848856B

  公开（公告）日：2016-08-03

  本发明公开了具有抗肿瘤活性的喜树碱衍生物，其为具有式(I)或式(II)所示结构的化合物、对映异构体或其药用盐。本发明的喜树碱类似物具有有益的药学性质，其对拓扑异构酶I和/或II具有抑制作用并具有抗肿瘤活性。实验证实本发明的化合物具有抗病毒活性，因而本发明的化合物可被用于不同的治疗应用中，如该化合物、其对映异构体或其药用盐应用于制备抗肿瘤药物方面。
• Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors
  作者：Raffaella Cincinelli、Loana Musso、Roberto Artali、Mario Guglielmi、Erminia Bianchino、Francesco Cardile、Fabiana Colelli、Claudio Pisano、Sabrina Dallavalle

  DOI：10.1016/j.ejmech.2017.11.021

  日期：2018.1

  compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the psammaplin A scaffold showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473

  最近的研究表明，由喜树碱衍生物和HDAC抑制剂组成的联合疗法具有增强的抗癌作用。为了在单一活性化合物中发挥这种协同作用，我们设计了同时靶向拓扑异构酶I和HDAC的新型双作用多价分子。特别地，包含喜树碱和psammaplin A支架的所选化合物显示出广谱的抗增殖活性，IC 50值在纳摩尔范围内。初步的体内结果表明对CD-1裸鼠原位异种移植的人间皮瘤原代细胞MM473有很强的抗肿瘤活性，并且具有很高的耐受性。
• Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents
  作者：Raffaella Cincinelli、Loana Musso、Roberto Artali、Mario B. Guglielmi、Ilaria La Porta、Carmela Melito、Fabiana Colelli、Francesco Cardile、Giacomo Signorino、Alessandra Fucci、Martina Frusciante、Claudio Pisano、Sabrina Dallavalle

  DOI：10.1371/journal.pone.0205018

  日期：——

  hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted

  最近的研究表明，在联合疗法中，HDAC抑制剂与喜树碱衍生物具有协同作用。为了利用这种协同作用，设计了同时靶向拓扑异构酶I和HDAC的新杂合分子。特别是，含有喜树碱和SAHA样模板的选定多价药物表现出广谱的抗增殖活性，IC50值在纳摩尔范围内。初步的体内结果表明对CD-1裸鼠原位异种移植的人间皮瘤原代细胞MM473有很强的抗肿瘤活性，并且具有很高的耐受性。
• ANTI-CANCER PHOSPHONATE ANALOGS
  申请人：Boojamra Constantine G.

  公开号：US20100022467A1

  公开（公告）日：2010-01-28

  The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗癌化合物、含有这些化合物的组合物以及包括给予这些化合物的治疗方法，还涉及用于制备这些化合物的过程和中间体。
• US7452901B2
  申请人：——

  公开号：US7452901B2

  公开（公告）日：2008-11-18