7-O-(4-aminobutyroyl)paclitaxel | 560060-75-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 7-O-(4-aminobutyroyl)paclitaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-9-(4-aminobutanoyloxy)-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 560060-75-5
• 化学式: C₅₁H₅₈N₂O₁₅
• 分子量: 939.026
• InChiKey: WGSUFHCJZSQCJF-OEDNWNMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  68.0
• 可旋转键数：
  14.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  253.38
• 氢给体数：
  4.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (S)-11-formy-4-乙基-4-羟基-1,12-二氢-4H-2-噁-6,12a-二氮杂-二苯并b,h芴-3,13-二酮 、 7-O-(4-aminobutyroyl)paclitaxel 在 4 A molecular sieve 作用下， 以 苯 为溶剂， 以60.7%的产率得到
  参考文献：
  名称：

  Antitumor agents 216. Synthesis and evaluation of paclitaxel–camptothecin conjugates as novel cytotoxic agents1

  摘要：

  Five conjugates (16-20) composed of a paclitaxel and a camptothecin derivative joined by an imine linkage were synthesized and evaluated as cytotoxic agents and as inhibitors of DNA topoisomerase I. All of the conjugates were potent inhibitors of tumor cell replication with improved activity relative to camptothecin. Significantly, compounds 16-18 were more active than paclitaxel and camptothecin against HCT-8 (colon adenocarcinoma) cell replication, and the spectrum of activity was different from a simple mixture of paclitaxel and camptothecin. All of the conjugates were significantly less potent than camptothecin as inhibitors of human topoisomerase I in vitro with 16, 18, and 19 showing only marginal activity at 50 M Based on activity against drug-resistant cell line replication, one could conclude that the conjugates are simply acting as 'weak taxanes', but the spectrum of activity, particularly against MCF-7 and HCT-8, strongly suggests that a novel mechanism of action has been achieved through conjugation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00040-3
• 作为产物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-3-phenyl-2-phenylmethoxycarbonyloxypropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(phenylmethoxycarbonylamino)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 palladium on activated charcoal 氢气 作用下， 生成 7-O-(4-aminobutyroyl)paclitaxel
  参考文献：
  名称：

  Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: Evaluation of novel conjugates as cytotoxic agents

  摘要：

  Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED50 = 14.8, 3.1, 19.4 nM compared with 55.5 nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.051

文献信息

• Branched drug-linker conjugates for the coupling to biological targeting molecules
  申请人：celares GmbH

  公开号：EP2913064A1

  公开（公告）日：2015-09-02

  The invention relates to novel conjugates comprising three molecules of a therapeutic agent and a branched, mono-reactive polyethylene glycol (PEG) based linker according to formula (I) or (II), a method for the preparation of such conjugates and use thereof. In addition, the invention relates to a pharmaceutical composition, a pharmaceutical kit comprising said conjugates for the treatment of a disease or disorder that can be at least in part alleviated by therapy.

  本发明涉及包括三分子治疗剂和一种基于分支、单反应性聚乙二醇（PEG）连接剂的新型共轭物，其符合公式（I）或（II），以及制备这种共轭物的方法和使用方法。此外，本发明还涉及一种药物组合物，一种包括所述共轭物的药物套装，用于治疗可以通过治疗至少在一定程度上缓解的疾病或疾病。
• Synthesis and characterization of novel natural product-Gd(III) MRI contrast agent conjugates
  作者：Eleni K. Efthimiadou、Maria E. Katsarou、Michael Fardis、Christos Zikos、Emmanuel N. Pitsinos、Athanasios Kazantzis、Leondios Leondiadis、Marina Sagnou、Dionisios Vourloumis

  DOI：10.1016/j.bmcl.2008.10.027

  日期：2008.12

  Several novel gadolinium chelates conjugated with paclitaxel, colchicine and thyroxine have been prepared as MRI contrast agents targeted to tubulin and thyroxine-binding globulin, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• [EN] INTERCELLULAR AND INTRACELLULAR PROXIMITY-BASED LABELING COMPOSITIONS AND SYSTEMS<br/>[FR] COMPOSITIONS ET SYSTÈMES DE MARQUAGE BASÉ SUR LA PROXIMITÉ INTRACELLULAIRE ET INTERCELLULAIRE
  申请人：UNIV PRINCETON

  公开号：WO2021174035A8

  公开（公告）日：2021-10-21