N-succinimidyl-4-(trimethylstannyl)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-succinimidyl-4-(trimethylstannyl)benzoic acid
• 英文别名: N-succinimidyl 4-(trimethylstannyl)benzoate；N-succinimidyl 4-trimethylstannylbenzoate；N-Succinimidyl-4-trimethylstannyl-benzoate；(2,5-dioxopyrrolidin-1-yl) 4-trimethylstannylbenzoate
• 化学式: C₁₄H₁₇NO₄Sn
• 分子量: 382.003
• InChiKey: UIVJCVJPQDZQOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.45
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-succinimidyl-4-(trimethylstannyl)benzoic acid 在 <76Br>Br(1-) 、 chloroamine-T 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.17h， 以60%的产率得到N-succinimidyl 4-[76Br]bromobenzoate
  参考文献：
  名称：

  Synthesis of N-Succinimidyl 4-[76Br]Bromobenzoate and its Use in Conjugation Labelling of Macromolecules.

  摘要：

  The Br-76 radiobromination of proteins and modified oligonucleotides by the use of N-succinimidyl 4-[Br-76]bromobenzoate are described. The labelled N-succinimidyl bromobenzoate was synthesised from the corresponding trimethyltin compound, N-succinimidyl 4-trimethylstannylbenzoate, in 45-60% isolated radiochemical yield with a specific radioactivity of 20-200 GBq mu mol(-1). The use of N-succinimidyl 4-[Br-76]bromobenzoate in conjugation with the proteins human serum albumin and chromogranin and with 5'-hexylamino-modified oligodeoxynucleotides (ODN) and its phosphorothioate analogues (S-ODN), is described. The oligonucleotide sequence chosen for this work is an antisense sequence for the m-RNA encoding for chromogranin in rat.

  DOI：

  10.3891/acta.chem.scand.53-0508

文献信息

• [EN] MINIMAL SAPONIN ANALOGUES, SYNTHESIS AND USE THEREOF<br/>[FR] ANALOGUES DE SAPONINE À STRUCTURE MINIMALE, SYNTHÈSE ET UTILISATION
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2015184451A1

  公开（公告）日：2015-12-03

  Truncated triterpene saponin analogues containing a trisaccharide or tetrasaccharide ester are disclosed. Also disclosed are pharmaceutical compositions comprising truncated saponin analogues and synthetic methods of producing the truncated saponin analogues. Another aspect of the present application relates to a method for immunizing a subject, comprising administering to the subject the pharmaceutical composition comprising a minimal saponin analogue and an antigen.

  披露了含有三糖或四糖酯的截短三萜皂苷类似物。还披露了包含截短皂苷类似物的药物组合物以及生产截短皂苷类似物的合成方法。本申请的另一个方面涉及一种免疫主体的方法，包括向主体施用包含最小皂苷类似物和抗原的药物组合物。
• Synthesis and radioiodination of some daunorubicin and doxorubicin derivatives
  作者：Senait Ghirmai、Eskender Mume、Vladimir Tolmachev、Stefan Sjöberg

  DOI：10.1016/j.carres.2004.10.014

  日期：2005.1

  the corresponding benzoic acid, resulting in good yields. Nicotinic acids and benzoic acids, activated with a succinimidyl group, were coupled to the amino group of daunorubicin to give the corresponding amide derivatives. Amine derivatives were obtained by the reductive amination of aromatic aldehydes with daunorubicin hydrochloride. The stannylated ester and amide derivatives were used as precursors

  柔红霉素和阿霉素是有效的癌症治疗药物。然而，其无差别的毒性阻碍了它们的临床疗效。可通过将药物封装在脂质体中并使用肿瘤靶向剂选择性靶向肿瘤细胞来解决此问题。此外，可以通过将俄歇电子发射体（125）I连接到柔红霉素和阿霉素衍生物上来增强抗肿瘤作用。在这种情况下，合成了柔红霉素和阿霉素的许多酯，酰胺和胺衍生物。柔红霉素的苯甲酸酯衍生物是通过14-溴双柔红霉素与相应的苯甲酸钾盐的亲核酯化反应合成的，收率很高。被琥珀酰亚胺基活化的烟酸和苯甲酸，将其与柔红霉素的氨基偶联以得到相应的酰胺衍生物。通过用盐酸柔红霉素对芳族醛进行还原胺化反应，可得到胺衍生物。甲锡烷基化的酯和酰胺衍生物用作放射性碘化的前体。使用氯胺-T作为氧化剂进行（125）I的放射性标记。优化的标记导致放射性碘化柔红霉素和阿霉素衍生物的高放射标记产率（85-95％）。胺的放射性碘化在活化的苯环的邻位进行，从而提供中等的放射化学产率（55-7
• Development of a minimal saponin vaccine adjuvant based on QS-21
  作者：Alberto Fernández-Tejada、Eric K. Chea、Constantine George、NagaVaraKishore Pillarsetty、Jeffrey R. Gardner、Philip O. Livingston、Govind Ragupathi、Jason S. Lewis、Derek S. Tan、David Y. Gin

  DOI：10.1038/nchem.1963

  日期：2014.7

  Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure–function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies. Adjuvants are used to increase the immune response to molecular vaccines. A minimal synthetic variant of the saponin natural product QS-21 has been developed as a potent, non-toxic adjuvant, enabling dissection of structural requirements in the triterpene domain and in vivo biodistribution studies to probe mechanisms of action.

  佐剂是添加到疫苗中的材料，用于增强对抗原的免疫反应。QS-21 是一种天然产品佐剂，目前正在许多疫苗临床试验中进行研究，但其使用受到稀缺性、毒性、不稳定性和分子作用机制不明等因素的限制。在本文中，我们描述了一种最小 QS-21 类似物的开发过程，这种类似物能将佐剂活性与毒性分离开来，为机理研究提供了一个强大的平台。我们发现，QS-21 的整个支链三糖结构域对于佐剂活性来说是不可或缺的，而之前被认为能与未知细胞靶点共价结合的 C4-醛取代基也不是必需的。生物分布研究表明，与减弱的变体相比，活性佐剂优先保留在注射部位和最近的引流淋巴结。总之，这些研究为了解皂苷的结构与功能关系提供了重要依据，为合成无毒佐剂提供了实用途径，并为详细的机理研究建立了平台。佐剂用于提高分子疫苗的免疫反应。皂苷天然产物 QS-21 的最小合成变体已被开发成一种强效、无毒的佐剂，从而能够剖析三萜结构域的结构要求，并通过体内生物分布研究来探究其作用机制。
• Synthesis and Preliminary Evaluation of ¹³¹I-Labeled FAPI Tracers for Cancer Theranostics
  作者：Huan Ma、Feize Li、Guohua Shen、Huawei Cai、Weihao Liu、Tu Lan、Yuanyou Yang、Jijun Yang、Jiali Liao、Ning Liu

  DOI：10.1021/acs.molpharmaceut.1c00566

  日期：2021.11.1

  candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two

  作为癌症治疗学的极好靶点，成纤维细胞活化蛋白 (FAP) 已成为癌症研究中极具吸引力的焦点。开发了一类具有N- (4-quinolinoyl)-Gly-(2-cyanopyrrolidine) 支架的 FAP 抑制剂 (FAPIs)，具有纳摩尔级亲和力和高选择性。与90 Y、177 Lu、225 Ac 和188 Re 相比，211 At 似乎更适合作为 FAPI 示踪剂的治疗候选者，这些示踪剂在肿瘤部位具有快速清除和短保留。因此，目前的研究报告了211 At 和131 I 标记的两种 FAPI 前体的合成以及131用于癌症治疗学的 I 标记的 FAPI 类似物。具有甲锡前体的 FAPI 变体已成功合成，并使用放射性碘去苯甲酸化反应用131 I 标记。对于131 I-FAPI-02 和131 I-FAPI-04，获得了两种放射性示踪剂，其放射化学纯度超过 99%，放射化学产率分别为 58.2
• Yngve, U.; Hedberg, E.; Tolmachev, V., Journal of Labelled Compounds and Radiopharmaceuticals, 1997, vol. 40, # c, p. 120 - 121
  作者：Yngve, U.、Hedberg, E.、Tolmachev, V.、Langstroem, B.

  DOI：——

  日期：——