N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide triflouroacetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide triflouroacetate
• 英文别名: N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazole-4-yl)pentanamide trifluoroacetate；HDA-biotin；N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide 2,2,2-trifluoroacetate；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-(6-aminohexyl)pentanamide;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₁₆H₃₀N₄O₂S
• 分子量: 456.53
• InChiKey: YLGCZXQORJGXCG-HZPCBCDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  159
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide triflouroacetate 在 偶氮二异丁腈 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery

  摘要：

  To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition-fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2'-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40-90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs.

  DOI：

  10.1016/j.jconrel.2020.09.013
• 作为产物：
  描述：

  (+)生物素-N-琥珀酰亚胺基酯 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(6-aminohexyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide triflouroacetate
  参考文献：
  名称：

  Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery

  摘要：

  To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition-fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2'-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40-90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs.

  DOI：

  10.1016/j.jconrel.2020.09.013

文献信息

• Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid
  作者：Marie-Adrienne Dude、Ulrich Kaeppler、Monika Herb、Markus Schiller、Franziska Schulz、Birgit Vedder、Saskia Heppner、Gabriele Pradel、Jiri Gut、Philip Rosenthal、Tanja Schirmeister、Matthias Leippe、Christoph Gelhaus

  DOI：10.3390/molecules14010019

  日期：——

  A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC50 values of 9.0 and 18.8 μM against Plasmodia.

  一系列依他尼酸衍生物被合成并筛选其对恶性疟原虫的体外活性，以及它们对重组表达的法西平-2和法西平-3的活性。该系列中活性最强的两种化合物对疟原虫的IC50值分别为9.0和18.8 μM。
• Design of a Mechanism-Based Probe for Neuraminidase To Capture Influenza Viruses
  作者：Chun-Ping Lu、Chien-Tai Ren、Yi-Ning Lai、Shih-Hsiung Wu、Wei-Man Wang、Jean-Yin Chen、Lee-Chiang Lo

  DOI：10.1002/anie.200501738

  日期：2005.10.28
• A versatile library of activity-based probes for fluorescence detection and/or affinity isolation of lipolytic enzymes
  作者：Heidrun Susani-Etzerodt、Hannes Schmidinger、Gernot Riesenhuber、Ruth Birner-Gruenberger、Albin Hermetter

  DOI：10.1016/j.chemphyslip.2006.06.018

  日期：2006.10

  This work describes the synthesis of a library of fluorescent and/or biotinylated alkylphosphonate inhibitors being reactive towards serine hydrolases, especially lipases and esterases. Fluorescent inhibitors can be used for sensitive and rapid detection of active proteins by gel electrophoresis. Biotinylated inhibitors are applicable for the enrichment and isolation of active enzymes. Functionality as well as the different detection methods of the synthesized inhibitors were successfully tested with an enzyme preparation, namely cholesterol esterase from porcine pancreas (ppCE). Moreover, a biotinylated inhibitor was employed to enrich ppCE on avidin beads. Hence, our set of phosphonate inhibitors can be used for the detection and/or isolation of active serine hydrolases. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
• RNA G-Quadruplexes in Kirsten Ras (<i>KRAS</i>) Oncogene as Targets for Small Molecules Inhibiting Translation
  作者：Giulia Miglietta、Susanna Cogoi、Jessica Marinello、Giovanni Capranico、Alexander S. Tikhomirov、Andrey Shchekotikhin、Luigi E. Xodo

  DOI：10.1021/acs.jmedchem.7b00622

  日期：2017.12.14

  The human KRAS transcript contains a G-rich 5'-UTR sequence (77% GC) harboring several G4 motifs capable to form stable RNA G-quadruplex (RG4) structures that can serve as targets for small molecules. A biotin streptavidin pull-down assay showed that 4,11-bis(2-aminoethylamino)anthra[2,3-b]furan-5,10-dione (2a) binds to RG4s in the KRAS transcript under low-abundance cellular conditions. Dual-luciferase assays demonstrated that 2a and its analogue 4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione (2b) repress translation in a dose-dependent manner. The effect of the G4-ligands on Panc-1 cancer cells has also been examined. Both 2a and 2b efficiently penetrate the cells, suppressing protein p21KRAS to < 10% of the control. The KRAS down-regulation induces apoptosis together with a dramatic reduction of cell growth and colony formation. In summary, we report a strategy to suppress the KRAS oncogene in pancreatic cancer cells by means of small molecules binding to RG4s in the 5'-UTR of mRNA.
• MULTIVALENT POLYMERS, PROCESSES FOR THEIR PREPARATION, AND THEIR USE FOR PREPARING BIOLOGICALLY ACTIVE COMPOUNDS.
  申请人：Novartis AG

  公开号：EP0866802A1

  公开（公告）日：1998-09-30