2'-NHS-succinylpaclitaxel | 245110-80-9

• 英文名称: 2'-NHS-succinylpaclitaxel
• 英文别名: Butanedioic acid, 1-[(1R)-2-[[(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl]oxy]-1-[(S)-(benzoylamino)phenylmethyl]-2-oxoethyl] 4-(2,5-dioxo-1-pyrrolidinyl) ester；1-O-[(1S,2R)-1-benzamido-3-[[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-2-benzoyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-15-yl]oxy]-3-oxo-1-phenylpropan-2-yl] 4-O-(2,5-dioxopyrrolidin-1-yl) butanedioate
• CAS: 245110-80-9
• 化学式: C₅₅H₅₈N₂O₁₉
• 分子量: 1051.07
• InChiKey: DXNRHBJDAAJTTD-CGFZLWGJSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  76
• 可旋转键数：
  21
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  291
• 氢给体数：
  3
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  环(-RGDFK) 、 2'-NHS-succinylpaclitaxel 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy

  摘要：

  The effective chemotherapy for glioblastoma multiform (GBM) requires a nanomedicine that can both penetrate the blood-brain barrier (BBB) and target the glioma cells subsequently. In this study, Transferrin (Tf)modified cyclo-[Arg-Gly-Asp-o-Phe-Lys] (c[RGDfK])-paclitaxel conjugate (RP) loaded micelle (TRPM) was prepared and evaluated for its targeting efficiency, antiglioma activity, and toxicity in vitro and in vivo. Tf modification significantly enhanced the cellular uptake of TRPM by primary brain microvascular endothelial cells (BMEC) to 2.4-fold of RP loaded micelle (RPM) through Tf receptor mediated endocytosis, resulting in a high drug accumulation in the brain after intravenous injection.The c[RGDfK] modified paclitaxel (PTX) was released from micelle subsequently and targeted to integrin overexpressed glioma cells in vitro, and showed significantly prolonged retention in glioma tumor and peritumoral tissue. Most importantly, TRPM exhibited the strongest antiglioma activity, as the mean survival time of mice bearing intracranial U-87 MG glioma treated with TRPM (42.8 days) was significantly longer than those treated with Tf modified PTX loaded micelle (TPM) (39.5 days), PTX loaded micelle (PM) (34.8 days), Taxol (33.6 days), and saline (34.5 days). Noteworthy, TRPM did not lead to body weight loss compared with saline and was less toxic than TPM. These results indicated that TRPM could be a promising nanomedicine for glioma chemotherapy.

  DOI：

  10.1021/mp200600t
• 作为产物：
  描述：

  紫杉醇 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 2'-NHS-succinylpaclitaxel
  参考文献：
  名称：

  两种互补的抗癌药物的共轭可将分子水凝胶作为共递送系统使用。

  摘要：

  我们在本通讯中报道了基于两种互补抗癌药物进行化疗的分子水凝胶系统的第一个例子。

  DOI：

  10.1039/c1cc16250k

文献信息

• [EN] HYDROGELATORS COMPRISING D-AMINO ACIDS<br/>[FR] COMPOSÉS FORMANT DES HYDROGELS COMPRENANT DES ACIDES AMINÉS D
  申请人：UNIV BRANDEIS

  公开号：WO2014074789A1

  公开（公告）日：2014-05-15

  Described herein are compounds comprising an oligopeptide and a non-steroidal antiinflammatory agent. The compounds self-assemble into supramolecular hydrogels and can be used as topical treatments for inflammatory conditions, such as osteoarthritis. Also described herein are oligopeptides compounds made from D-amino acid residues that form supramolecular hydrogels. The compounds may be functionalized with active agents, such as anticancer therapeutic agents, antiinflammatory agents, or imaging agents, therefore providing new mechanisms for delivery of active agents.

  本文描述了包含寡肽和非甾体抗炎药物的化合物。这些化合物自组装成超分子水凝胶，可用作治疗炎症病症，如骨关节炎的局部治疗。本文还描述了由D-氨基酸残基制成的寡肽化合物，形成超分子水凝胶。这些化合物可以与活性剂（如抗癌治疗剂、抗炎药物或成像剂）功能化，从而提供了传递活性剂的新机制。
• PRODRUG COMPOSITIONS, PRODRUG NANOPARTICLES, AND METHODS OF USE THEREOF
  申请人：Washington University

  公开号：US20160279060A1

  公开（公告）日：2016-09-29

  The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof.

  本发明涵盖了前药组合物、包含一种或多种前药的纳米粒子，以及其使用方法。
• TRANSMUCOSAL DELIVERY OF PHARMACEUTICAL ACTIVE SUBSTANCES
  申请人：JON Sangyong

  公开号：US20070292387A1

  公开（公告）日：2007-12-20

  Provided is a conjugate including a pharmacologically active substance covalently bound to chitosan or its derivative and a method for transmucosal delivery of a pharmacologically active substance using the same. Specifically, a conjugate includes a pharmacologically active substance covalently bound via a linker to chitosan; and a pharmaceutical composition for transmucosal administration of a drug includes the aforementioned conjugate and a pharmaceutically acceptable carrier. Further provided is a method for in vivo delivery of a pharmacologically active substance via a transmucosal route, by covalent binding of the active substance with chitosan or its derivative via a linker. The conjugate in accordance with the present invention exhibits excellent absorption rate and biocompatibility in biological mucous membranes, particularly mucous membranes of the alimentary canal (especially the gastrointestinal tract), in vivo degradability, and superior bioavailability even with oral administration, thus enabling treatment of diseases via oral administration of a drug.

  提供的是一个包括药理活性物质与壳聚糖或其衍生物共价结合的共轭物，以及使用该共轭物进行药理活性物质经粘膜途径传递的方法。具体来说，该共轭物包括通过连接剂与壳聚糖共价结合的药理活性物质；以及用于经粘膜途径给药的药物组合物包括上述共轭物和药学上可接受的载体。此外，提供了一种通过药理活性物质与壳聚糖或其衍生物通过连接剂共价结合的方式，经粘膜途径在体内传递药理活性物质的方法。根据本发明的共轭物在生物粘膜，特别是消化道（尤其是胃肠道）的粘膜中表现出优异的吸收速率和生物相容性，在体内可降解性，以及即使口服也具有优越的生物利用度，从而使得通过口服给药治疗疾病成为可能。
• A New NT4 Peptide-Based Drug Delivery System for Cancer Treatment
  作者：Jlenia Brunetti、Sara Piantini、Marco Fragai、Silvia Scali、Giulia Cipriani、Lorenzo Depau、Alessandro Pini、Chiara Falciani、Stefano Menichetti、Luisa Bracci

  DOI：10.3390/molecules25051088

  日期：——

  selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetrabranched peptide known as NT4, which is a promising cancer theranostic by virtue of its high cancer selectivity. We developed NT4 directly conjugated with one, two, or three

  开发选择性肿瘤靶向剂以将多个单位的化疗药物递送至癌组织将提高治疗效果并极大地推进癌症治疗的进展。在这里，我们报告了一种基于称为 NT4 的四分支肽的新药物递送系统，由于其高癌症选择性，它是一种很有前途的癌症治疗诊断学。我们开发了 NT4 与一个、两个或三个单位的紫杉醇和基于 NT4 的纳米系统直接偶联，使用 NIR 发射量子点，加载 NT4 肿瘤靶向剂并与紫杉醇偶联，以获得 NT4-QD-PTX旨在同时检测和杀死肿瘤细胞的纳米装置。当在人结肠腺癌细胞系 HT-29 上测试时，NT4-QD-PTX 的选择性结合和体外细胞毒性高于未标记的 QD-PTX。
• Conjugate comprising a neurotensin receptor ligand
  申请人：3B Pharmaceuticals GmbH

  公开号：EP2954933A1

  公开（公告）日：2015-12-16

  The present invention is related to a conjugate comprising a structure of general formula (I)         [TM1] - [AD1] - [LM] - [AD2] - [TM2]     (I), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (II): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (III) wherein ALK' is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及一种包含一般式（I）结构的结合物，其中TM1是第一靶向基团，第一靶向基团能够结合到第一个靶标，AD1是第一适配基团或者不存在，LM是连接基团或者不存在，AD2是第二适配基团或者不存在，TM2是第二靶向基团，第二靶向基团能够结合到第二个靶标；其中第一靶向基团和/或第二靶向基团是式（II）化合物之一：其中R1选自氢、甲基和环丙基甲基组成的群；AA-COOH是选自2-氨基-2-环戊烷羧酸、环己基甘氨酸和9-氨基-双环[3.3.1]壬烷-9-羧酸组成的氨基酸；R2选自（C1-C6）烷基、（C3-C8）环烷基、（C3-C8）环烷基甲基、卤素、硝基和三氟甲基的群；ALK是（C2-C5）烷基亚基；R3、R4和R5各自独立地选自氢和（C1-C4）烷基，但是在R3、R4和R5中的一个符合以下式（III）：其中ALK'是（C2-C5）烷基亚基；R6选自氢和（C1-C4）烷基；R7是键；或其药理学上可接受的盐、溶剂或水合物。