(9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H)-dione | 367452-96-8

• 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: (9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H)-dione
• 英文别名: (9S)-1-Amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione；(10S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione
• CAS: 367452-96-8
• 化学式: C₂₄H₂₂FN₃O₄
• 分子量: 435.455
• InChiKey: ZVYVPGLRVWUPMP-ODOSRFNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H)-dione 、 乙酸酐 在 三乙胺 作用下， 以 甲醇 为溶剂， 生成 N-[(10S,23R)-10-ethyl-18-fluoro-10-hydroxy-19-methyl-5,9-dioxo-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaen-23-yl]acetamide 、 N-[(1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]acetamide
  参考文献：
  名称：

  Exatecan 甲磺酸盐的替代合成

  摘要：

  描述了合成 Exatecan 甲磺酸盐的替代方法。已开发出由化合物5制备 Exatecan 的 7 步合成路线。第一步碘化反应具有更好的选择性，有效避免了不需要的位置异构体。引入硝基、烯烃和亚硝基后一步同时还原，避免了过度的逐步还原。通过叔丁酯与三氯化铟的分子内傅克酰化成功合成了环状化合物(9)。利用脱乙酰反应中的差向异构化从母液中回收exaltecan，该合成路线总收率达到12%。

  DOI：

  10.1016/j.tetlet.2024.154912

文献信息

• CAMPTOTHECIN DERIVATIVE, AND PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION AND APPLICATION
  申请人：Zhou Wenqiang

  公开号：US20140107342A1

  公开（公告）日：2014-04-17

  The present invention relates to a camptothecin derivative having a structure as represented by Formula (II), in which X n+ is selected from H + , K + , Na + , Li + , Mg 2+ , Ca 2+ , Zn 2+ , Fe 3+ , and ammonium ion, while R 1 , R 2 , R 3 , and R 4 independently represent a hydrogen, a hydroxyl group, a nitro group, a cyano group, a halogen, a carboxyl group, an optionally substituted amino group, a silicon-containing group, a monocyclic aryloxy group, an optionally substituted C1-C6 alkoxy group, an optionally substituted C1-C6 alkylcarbonyl group, an optionally substituted C1-C6 alkyl group, or an optionally substituted C3-C6 cycloalkyl group; alternatively, R 1 and R 2 are connected via one to three other atoms to form a heterocyclic ring; and in another embodiment, R 3 and R 4 are oxygen atoms and connected via —O—(CH 2 ) n —O—, forming a ring, in which n=I or 2. The compound has great water-solubility, chemical stability, and great efficacy in treatment on cancer.

  本发明涉及一种具有如下式（II）所表示结构的紫杉醌衍生物，其中X n+ 选自H + 、K + 、Na + 、Li + 、Mg 2+ 、Ca 2+ 、Zn 2+ 、Fe 3+ 和铵离子，而R 1 、R 2 、R 3 和R 4 独立地代表氢、羟基、硝基、氰基、卤素、羧基、可选择取代的氨基、含硅基团、单环芳氧基团、可选择取代的C1-C6烷氧基团、可选择取代的C1-C6烷基羰基团、可选择取代的C1-C6烷基团，或可选择取代的C3-C6环烷基团；或者，R 1 和R 2 通过一到三个其他原子连接形成杂环环；在另一实施例中，R 3 和R 4 是氧原子，并通过—O—(CH 2 ) n —O—连接形成一个环，其中n=1或2。该化合物具有很高的水溶性、化学稳定性，并在癌症治疗中具有很高的功效。
• BLOCK COPOLYMERS FOR STABLE MICELLES
  申请人：Intezyne Technologies, Inc.

  公开号：US20130280306A1

  公开（公告）日：2013-10-24

  The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

  本发明涉及聚合物化学领域，更具体地说是涉及多区块共聚物以及包含相同的多区块共聚物胶束。本发明的组合物适用于药物输送应用。
• ANTIBODY-DRUG CONJUGATE
  申请人：DAIICHI SANKYO COMPANY, LIMITED

  公开号：US20150297748A1

  公开（公告）日：2015-10-22

  As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L 1 -L 2 -L P -NH—(CH 2 ) n 1 -L a -L b -L c - wherein the antibody is connected to the terminal of L 1 , and the antitumor compound is connected to the terminal of L c with the nitrogen atom of the amino group at position 1 as a connecting position.

  提供了一种抗肿瘤药物，其在抗肿瘤效果和安全性方面均表现出色，其中通过以下公式表示的抗肿瘤化合物通过具有以下公式表示的结构的连接剂与抗体结合：-L1-L2-LP-NH-（CH2）n1-La-Lb-Lc-其中抗体连接到L1的末端，抗肿瘤化合物连接到Lc的末端，并以氨基位置1的氮原子作为连接位置。
• [EN] ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS<br/>[FR] COMPOSÉS CIBLANT DES RÉCEPTEURS HORMONAUX NUCLÉAIRES ANTICANCÉREUX
  申请人：NUVATION BIO INC

  公开号：WO2022204184A1

  公开（公告）日：2022-09-29

  The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.

  该披露涉及从核类固醇受体结合物中衍生出的抗癌化合物，包括含有相同化合物的产品，以及它们的使用和制备方法。
• MEDICINAL COMPOSITIONS CONTAINING CAMPTOTHECIN DERIVATIVE AND PH REGULATING AGENT
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1310254A1

  公开（公告）日：2003-05-14

  A pharmaceutical preparation which ensures stability and solubility of a hexacyclic camptothecin derivative prepared by adding a ring having a water-soluble group to camptothecin, wherein a pH-adjusting substance and, as occasion demands, a sugar or a sugar alcohol are added to the hexacyclic camptothecin derivative.

  一种药物制剂，可确保通过在喜树碱中添加具有水溶性基团的环而制备的六环喜树碱衍生物的稳定性和可溶性，其中在六环喜树碱衍生物中添加了一种 pH 值调节物质，并根据需要添加了一种糖或糖醇。