[2-({5-oxo-5-[(triisopropylsilyl)oxy]pentan-2-yl}disulfanyl)phenyl]acetic acid | 1334524-25-2

• 分子结构分类: 有机化合物
• 英文名称: [2-({5-oxo-5-[(triisopropylsilyl)oxy]pentan-2-yl}disulfanyl)phenyl]acetic acid
• 英文别名: 2-(2-5-oxo-5-(triisopropylsilyloxy)pentan-2-yldisulfanylphenyl)acetic acid；2-[2-[[5-Oxo-5-tri(propan-2-yl)silyloxypentan-2-yl]disulfanyl]phenyl]acetic acid
• CAS: 1334524-25-2
• 化学式: C₂₂H₃₆O₄S₂Si
• 分子量: 456.743
• InChiKey: JCULEPIVQIVOJQ-UHFFFAOYSA-N

物化性质

• 沸点：
  511.6±50.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.94
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [2-({5-oxo-5-[(triisopropylsilyl)oxy]pentan-2-yl}disulfanyl)phenyl]acetic acid 在 吡啶 、 4-二甲氨基吡啶 、 氢氟酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 58.0h， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-15-[(2R,3S)-2-[2-[2-[[5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  [EN] SYNTHESIS OF NOVEL ASYMMETRIC BOW-TIE PAMAM DENDRIMER-BASED CONJUGATES FOR TUMOR-TARGETING DRUG DELIVERY
  [FR] SYNTHÈSE DE NOUVEAUX CONJUGUÉS ASYMÉTRIQUES À BASE D'UN DENDRIMÈRE PAMAM EN NŒUD PAPILLON POUR ADMINISTRATION DE MÉDICAMENTS CIBLÉE VERS UNE TUMEUR

  摘要：

  本公开涉及一种公式为Vm-D-C-D'-(T-F)n的基于树状聚合物的结合物，该结合物对于肿瘤靶向药物传递很有用。不对称树状聚合物的使用可以实现特定的靶向以及合成的可重复性。

  公开号：

  WO2015038493A1
• 作为产物：
  描述：

  在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 [2-({5-oxo-5-[(triisopropylsilyl)oxy]pentan-2-yl}disulfanyl)phenyl]acetic acid
  参考文献：
  名称：

  Targeted and armed oncolytic adenovirus via chemoselective modification

  摘要：

  Oncolytic adenoviruses (Ads) are an emerging alternative therapy for cancer; however, clinical trial have not yet demonstrated sufficient efficacy. When oncolytic Ads are used in combination with taxoids a synergistic increase in both cytotoxicity and viral replication is observed. In order to generate a next generation oncolytic adenovirus, virion were physically conjugated to a highly potent taxoid, SB-T-1214, and a folate targeting motif. Conjugation was enabled via the metabolic incorporation of non-canonical monosaccharides (O-GlcNAz) and amino acids (homopropargylglycine), which served as sites for chemoselective modification. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.039

文献信息

• [EN] THERAPEUTIC AGENT FOR TREATING TUMORS<br/>[FR] AGENT THÉRAPEUTIQUE POUR LE TRAITEMENT DE TUMEURS
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2015143092A1

  公开（公告）日：2015-09-24

  The present disclosure relates to a therapeutic agent of the formula: Z-C(=O)-(CH2)n-ϕ-S-S-(CRR')m-(CH2)p-C(=O)- NH-(CH2)q-NH-Y[NH-(CH2)r-X-T-W][NH-(CH2-CH-O)t (CH2)s-NH-V] Formula I or a pharmaceutically acceptable salt thereof, useful for treating tumors, including cancers. Where the compound of Formula I also contains a radionuclide or an imaging agent or both, the compound of formula I is a theranostic agent useful for treating and diagnosing tumors, including cancers.

  本公开涉及一种治疗剂，其化学式为：Z-C(=O)-(CH2)n-ϕ-S-S-(CRR')m-( )p-C(=O)- NH-( )q-NH-Y[NH-( )r-X-T-W][NH-( -CH-O)t ( )s-NH-V] 化学式I或其药学上可接受的盐，用于治疗肿瘤，包括癌症。化合物I的化学式还包含放射性核素或成像剂或两者的情况下，化合物I是一种治疗和诊断肿瘤，包括癌症的治疗剂。
• Design, synthesis and application of fluorine-labeled taxoids as 19F NMR probes for the metabolic stability assessment of tumor-targeted drug delivery systems
  作者：Joshua D. Seitz、Jacob G. Vineberg、Longfei Wei、Jonathan F. Khan、Brendan Lichtenthal、Chi-Feng Lin、Iwao Ojima

  DOI：10.1016/j.jfluchem.2014.08.006

  日期：2015.3

  tumor-targeting module, were designed and synthesized as 19F NMR probes. Fluorine atoms and CF3 groups were strategically incorporated into the conjugates to investigate the mechanism of linker cleavage and factors that influence their plasma and metabolic stability by real-time monitoring with 19F NMR. Time-resolved 19F NMR study on probe 1 disclosed a stepwise mechanism for release of a fluorotaxoid

  新型的靶向肿瘤的药物结合物BLT-F2（1）和BLT-S-F6（2），以氟类紫杉醇为战斗部，基于机制的自消灭性二硫键，以生物素为肿瘤靶向模块，被称为“ BLT-F2（1）”和“ BLT-S-F6（2）”。设计并合成为19F NMR探针。将氟原子和CF3基团策略性地结合到缀合物中，以通过19F NMR实时监测来研究接头裂解的机制以及影响其血浆和代谢稳定性的因素。对探针1进行时间分辨的19 F NMR研究揭示了一种逐步释放氟类紫杉醇的机制，而其他分析方法可能未检测到这种机制。探针2设计为在紫杉醇部分带有两个 基团，以作为“ 3-FAB”报告基因，以提高灵敏度，并使用聚乙二醇低聚物插入物来提高溶解度。由于关键信号/峰与生物系统中高度复杂的成分所产生的背景重叠，因此通过HPLC和1H NMR对血浆或细胞培养基中药物偶联物的接头稳定性和反应性进行干净的分析很麻烦。因此，使用19 F NMR将为该
• Design, Synthesis, and Biological Evaluations of Tumor-Targeting Dual-Warhead Conjugates for a Taxoid–Camptothecin Combination Chemotherapy
  作者：Jacob G. Vineberg、Edison S. Zuniga、Anushree Kamath、Ying-Jen Chen、Joshua D. Seitz、Iwao Ojima

  DOI：10.1021/jm500631u

  日期：2014.7.10

  Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two warheads, self-immolative disulfide linkers for drug release, biotin as the tumor-targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR (BR+, biotin receptor overexpressed) and WI38 (BR-, normal) cell lines in the absence and presence of glutathione (GSH), which is an endogenous thiol that triggers drug release inside the cancer cells. With the GSH and resuspension protocol, 2 exhibited IC50 values of 3.22-9.80 nM against all BR+ cancer cell lines, and 705 nM against WI38. Thus, there was a two orders of magnitude higher selectivity to cancer cells. Also, a clear cooperative effect was observed for the taxoid-camptothecin combination when two drugs were delivered to the cancer cells specifically in the form of a dual-warhead conjugate.