7-hydroxymethyl-10-hydroxycamptothecin | 86639-61-4

• 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: 7-hydroxymethyl-10-hydroxycamptothecin
• 英文别名: SN-38；(19S)-19-ethyl-7,19-dihydroxy-10-(hydroxymethyl)-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-14,18-dione
• CAS: 86639-61-4
• 化学式: C₂₁H₁₈N₂O₆
• 分子量: 394.384
• InChiKey: JFYLHBNJLVAXBS-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-hydroxymethyl-10-hydroxycamptothecin 在 甲酸 、 盐酸羟胺 、 sodium formate 作用下， 反应 9.0h， 生成 (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：

  7-hydroxymethylcamptothecin 在 硫酸 、 双氧水 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 溶剂黄146 为溶剂， 反应 4.0h， 生成 7-hydroxymethyl-10-hydroxycamptothecin
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 20(S)-Camptothecin Derivatives: A-Ring Modified and 7,10-Disubstituted Camptothecins.

  摘要：

  在A环上具有硝基、氨基、氯、溴、羟基和甲氧基的20(S)-喜树碱衍生物被合成出来。通过在三氟乙酸中用四乙酸铅处理，B环氢化的喜树碱（2a）被转化为10-羟基喜树碱（6e）。通过N-氧化物（9）的光反应得到了10-取代的衍生物（6）。对A环修饰的喜树碱的细胞毒性进行了体外KB细胞和小鼠中的白血病L1210的评估。鉴定出7-乙基-10-羟基喜树碱（6i）作为一个有潜力的衍生物，可进一步进行修饰。

  DOI：

  10.1248/cpb.39.3183

文献信息

• 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。
• Camptothecin derivatives, processes for preparing same, formulations containing such derivatives and their use
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP0074256B1

  公开（公告）日：1986-11-20
• US4473692A
  申请人：——

  公开号：US4473692A

  公开（公告）日：1984-09-25
• US4545880A
  申请人：——

  公开号：US4545880A

  公开（公告）日：1985-10-08
• US7452901B2
  申请人：——

  公开号：US7452901B2

  公开（公告）日：2008-11-18