7-ethyl-9-amino-20(S)-camptothecin | 124622-68-0

• 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: 7-ethyl-9-amino-20(S)-camptothecin
• 英文别名: (19S)-8-amino-10,19-diethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
• CAS: 124622-68-0
• 化学式: C₂₂H₂₁N₃O₄
• 分子量: 391.426
• InChiKey: XEZHQWJDQCESCS-QFIPXVFZSA-N

物化性质

• 沸点：
  810.4±65.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (氯亚甲基)二甲基氯化铵 、 7-ethyl-9-amino-20(S)-camptothecin 以 N,N-二甲基甲酰胺 为溶剂， 生成 N'-((S)-4,11-Diethyl-4-hydroxy-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-10-yl)-N,N-dimethyl-formamidine; hydrochloride
  参考文献：
  名称：

  Synthesis and antitumor activity of a new class of water soluble camptothecin derivatives

  摘要：

  A new family of water soluble camptothecin derivatives is described. Their synthesis, in vitro cytotoxicity, and in vivo antitumor activity is reported. Compounds 5a and 5c displayed excellent in vivo antitumor activity both ip and iv.

  DOI：

  10.1016/0960-894x(96)00083-2
• 作为产物：
  描述：

  7-乙基-10-羟基喜树碱 在 4-二甲氨基吡啶 、 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 甲酸 、 硝酸 、 三乙胺 作用下， 以 硫酸 为溶剂， 生成 7-ethyl-9-amino-20(S)-camptothecin
  参考文献：
  名称：

  Synthesis and antitumor activity of a new class of water soluble camptothecin derivatives

  摘要：

  A new family of water soluble camptothecin derivatives is described. Their synthesis, in vitro cytotoxicity, and in vivo antitumor activity is reported. Compounds 5a and 5c displayed excellent in vivo antitumor activity both ip and iv.

  DOI：

  10.1016/0960-894x(96)00083-2

文献信息

• [EN] CHOLESTEROL/BILE ACID/BILE ACID DERIVATIVE-MODIFIED THERAPEUTIC ANTI-CANCER DRUGS<br/>[FR] MEDICAMENTS ANTICANCEREUX THERAPEUTIQUES MODIFIES PAR LE CHOLESTEROL/L'ACIDE BILIAIRE/LES DERIVES D'ACIDE BILIAIRE
  申请人：SONUS PHARMA INC

  公开号：WO2005118612A1

  公开（公告）日：2005-12-15

  Cholesterol-modified anti-cancer therapeutic drug compounds, bile-acid-modified anti-cancer therapeutic drug compounds, and bile-acid-derivative-modified anti-cancer therapeutic drug compounds; emulsion, microemulsion, and micelle formulations that include the compounds, methods for administering the compounds and formulations; and methods for treating cancer using the compounds and formulations.

  胆固醇修饰的抗癌治疗药物化合物，胆酸修饰的抗癌治疗药物化合物，以及胆酸衍生物修饰的抗癌治疗药物化合物；包括这些化合物的乳剂、微乳剂和胶束配方，用于给药这些化合物和配方的方法；以及使用这些化合物和配方治疗癌症的方法。
• LIPOPHILIC ANTICANCER DRUG COMPOUNDS, COMPOSITIONS AND RELATED METHODS
  申请人：Zhang Yuehua

  公开号：US20070142331A1

  公开（公告）日：2007-06-21

  Lipophilic anticancer drug compounds, compositions that include the compounds, and methods for treating a cell proliferative disease using the compounds.

  亲脂性抗癌药物化合物，包括该化合物的组合物，以及使用该化合物治疗细胞增殖性疾病的方法。
• LIPOPHILIC DI(ANTICANCER DRUG) COMPOUNDS, COMPOSITIONS, AND RELATED METHODS
  申请人：Zhang Yuehua

  公开号：US20070141093A1

  公开（公告）日：2007-06-21

  Lipophilic di(anticancer drug) compounds, compositions that include the compounds, and methods for treating a cell proliferative disease using the compounds.

  亲脂性双(抗癌药物)化合物，包括这些化合物的组合物，以及使用这些化合物治疗细胞增殖性疾病的方法。
• Synthesis and Antitumor Activity of 20(S)-Camptothecin Derivatives. A-Ring-Substituted 7-Ethylcamptothecins and Their E-Rig-Modified Water-Soluble Derivatives.
  作者：Takashi YAEGASHI、Seigo SAWADA、Hiroshi NAGATA、Tomio FURUTA、Teruo YOKOKURA、Tadashi MIYASAKA

  DOI：10.1248/cpb.42.2518

  日期：——

  Twenty-six novel A-ring-modified 7-ethylcamptothecins (6) were synthesized by Friedlander's condensation of the chiral tricyclic ketone (5) with aminopropiophenones (4). The compounds substituted with fluorine at the 11 position showed strong cytotoxicity to KB and L1210 cells. The 11-fluoro derivatives also exhibited strong inhibitory activity on DNA topoisomerase I. Nine compounds 6 with four to ten times stronger cytotoxicity than that of camptothecin were selected and converted into water-soluble 17-O-acyl amide derivatives (8). Compounds 8e (10-Me, O-COCH2CH2SCH3) and 8f (11-F, O-COC2H5) showed activity towards Meth A in mice that was comparable to that of CPT-11, at lower doses than CPT-11.

  合成了二十六种新型A环修饰的7-乙基喜树碱（6），通过Friedlander缩合反应，将手性三环酮（5）与氨基丙酮芳香化合物（4）进行反应。11位取代氟的化合物对KB细胞和L1210细胞表现出强烈的细胞毒性。11-氟衍生物在DNA拓扑酶I上的抑制活性也很强。选择了九种细胞毒性比喜树碱强四到十倍的化合物6，并将其转化为水溶性的17-O-酰胺衍生物（8）。化合物8e（10-甲基，O-COCH2CH2SCH3）和8f（11-氟，O-COC2H5）在小鼠中对Meth A的活性与CPT-11相当，且所需剂量低于CPT-11。
• Camptothecin derivatives and process for preparing same
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP0325247A1

  公开（公告）日：1989-07-26

  New camptothecin derivatives and a process for preparing same are disclosed, which are represented by the general formula: wherein R¹ represents a lower alkyl group, R² represents a hydrogen atom or an amino, hydroxyl, lower acylamino or lower alkoxy group, R³ represents a hydrogen or halogen atom or a lower alkyl, hydroxyl, lower alkoxy, nitro, amino, cyano or di(lower alkyl)amino group, R⁴ represents a hydrogen or halogen atom or a lower alkyl, hydroxyl, lower alkoxy, lower alkylthio, amino, cyano or di(lower alkyl)amino group, and R⁵ represents a hydrogen or halogen atom or a hydroxyl or lower alkoxy group, with the proviso that all of the R², R³, R⁴ and R⁵ substituents should not be a hydrogen atom and also that if any one of the R², R³, R⁴ and R⁵ is a hydroxyl or lower alkoxy group, all of the other three substituents should not be a hydrogen atom. The new camptothecin derivatives are useful as anti-tumor drugs or intermediates therefor.

  本发明公开了新喜树碱衍生物及其制备方法，它们由通式表示： 其中 R¹ 代表低级烷基，R² 代表氢原子或氨基、羟基、低级酰氨基或低级烷氧基，R³ 代表氢原子或卤素原子或低级烷基、羟基、低级烷氧基、硝基、氨基、氰基或二（低级烷基）氨基，R⁴ 代表氢原子或卤素原子或低级烷基、羟基、低级烷氧基、低级烷硫基、氨基、氰基或二（低级烷基）氨基，以及 R⁵ 代表氢原子或卤素原子或低级烷基、羟基、低级烷氧基、低级烷硫基、氨基、氰基或二（低级烷基）氨基、R⁴代表氢原子、卤素原子或低级烷基、羟基、低级烷氧基、低级烷硫基、氨基、氰基或二（低级烷基）氨基，R⁵代表氢原子、卤素原子或羟基或低级烷氧基，但所有 R²、R³、R⁴ 和 R⁵ 取代基都不能是氢原子，而且如果 R²、R³、R⁴ 和 R⁵ 中的任何一个是羟基或低级烷氧基，则其他三个取代基都不能是氢原子。新喜树碱衍生物可用作抗肿瘤药物或其中间体。