tert-butyldimethyl(4-isocyanatobenzyloxy)silane | 922173-23-7

• 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: tert-butyldimethyl(4-isocyanatobenzyloxy)silane
• 英文别名: tert-butyl-[(4-isocyanatophenyl)methoxy]dimethylsilane；tert-Butyl[(4-isocyanatophenyl)methoxy]dimethylsilane；tert-butyl-[(4-isocyanatophenyl)methoxy]-dimethylsilane
• CAS: 922173-23-7
• 化学式: C₁₄H₂₁NO₂Si
• 分子量: 263.412
• InChiKey: CBXOVKFTFPXWOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyldimethyl(4-isocyanatobenzyloxy)silane 在 lithium hydroxide 、 Amberlite IR-120 (H⁺ form) 、 水 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.5h， 生成 N-[4-(daunorubicin-N-carbonyloxymethyl)phenyl] O-β-D-galactopyranosyl carbamate
  参考文献：
  名称：

  Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy

  摘要：

  A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-beta-glycoside were designed to be activated by beta-glucuronidase or beta-galactosidase. Prodrugs with -chloro, bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -beta-glucuronyl, -beta-glucosyl or -beta-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly beta-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective beta-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2 h. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00095-4
• 作为产物：
  描述：

  对氨基苯甲醇 在 咪唑 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 27.0h， 生成 tert-butyldimethyl(4-isocyanatobenzyloxy)silane
  参考文献：
  名称：

  用于四嗪触发的细胞内醇释放的自消灭性接头的开发。

  摘要：

  生物正交降解反应是前药活化的一种有前途的策略，因为它们涉及键断裂以释放目标分子。反式-环辛烯（TCO）-四嗪逆电子需求的Diels-Alder反应已在体内广泛用于降低胺前药的含量，但是，对含醇生物活性化合物的释放研究较少。在这里，我们报告了与四嗪触发器反应后释放OH分子的TCO-氨基甲酸酯苄基醚自消灭性连接体。苄基醚连接物被证明是高度稳定的，并且在与四嗪类反应后可以在生理条件下迅速释放出醇。使用荧光TCO-苄基醚-香豆素探针和不同的3种化合物，通过荧光和HPLC分析系统地检查了机理和降解率。6-取代的四嗪衍生物。这项研究表明，降级迅速发生（t1 / 2 = 27分钟），环加成步骤在几秒钟内（t1 / 2 = 7 s）发生，反应速率约为100 M-1 s-1。重要的是，该反应与活生物体相容，如在活大肠杆菌存在下抗菌化合物三氯生前药的降解证明的那样，该反应通过释放的“ OH-活性药物”的作用导

  DOI：

  10.1039/c9ob01167f

文献信息

• Highly Diastereoselective Synthesis of Anomeric β-O-Glycopyranosyl Carbamates from Isocyanates
  作者：Ruben G. G. Leenders、Rob Ruytenbeek、Eric W. P. Damen、Hans W. Scheeren

  DOI：10.1055/s-1996-4377

  日期：1996.11

  1-β-O-Glycopyranosyl carbamates are prepared with practically 100% β-diastereoselectivity from anomerically unprotected glycopyranosides and isocyanates. The isocyanates are prepared in situ from carboxylic acids via acyl azides.

  1-β-O-Glycopyranosyl carbamates 是通过在几乎 100% β-对映选择性下，从无保护的α-糖苷和异氰酸酯制备的。异氰酸酯则是由羧酸通过酰基叠氮化物原位制备得来的。
• [EN] CYCLOPENTAIMIDAZOLONES FOR THE TREATMENT OF CANCER<br/>[FR] CYCLOPENTAIMIDAZOLONES POUR LE TRAITEMENT DU CANCER
  申请人：BROAD INST INC

  公开号：WO2019173506A1

  公开（公告）日：2019-09-12

  Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/or prophylaxis of proliferative diseases, including cancer, and more specifically, pancreatic cancer.

  本文提供了一些用于治疗各种增生性疾病的化合物。这些化合物及其药用盐可制成药物组合物，并可用于治疗和/或预防增生性疾病的方法，包括癌症，更具体地说，胰腺癌。
• 丹曲林前药及其用法
  申请人：伊格尔研究实验室有限公司

  公开号：CN111344286A

  公开（公告）日：2020-06-26

  本公开涉及丹曲林前药，其组合物，及其在疾病治疗中的用法。
• Esters Of Glucuronide Prodrugs Of Anthracyclines And Method Of Preparation And Use In Tumor-Selective Chemotherapy
  申请人：Aben Rene Wilhelmus Marie

  公开号：US20090227617A1

  公开（公告）日：2009-09-10

  The invention relates to novel esters and in particular to some novel esters of glucuronide prodrugs of anthracyclines having tunable water-solubility, their synthesis and use in tumor-selective chemotherapy. It appeared that in the final step in the synthesis of these prodrugs, i.e. the coupling of the glucuronide spacer moiety to the parent drug molecule, protection of the sugar hydroxyls is, surprisingly, no longer required. A process for the preparation of these unprotected sugar spacer moieties is also disclosed.

  该发明涉及新型酯类化合物，特别是一些新型葡萄糖醛酸盐前药的酯类化合物，其具有可调节的水溶性，以及它们在肿瘤选择性化疗中的合成和应用。在这些前药的合成的最后一步中，即将葡萄糖醛酸盐间隔基与母药分子偶联时，令人惊讶的是，不再需要保护糖羟基。还公开了一种制备这些未保护糖间隔基的过程。
• The azaquinone-methide elimination: comparison study of 1,6- and 1,4-eliminations under physiological conditions
  作者：Rotem Erez、Doron Shabat

  DOI：10.1039/b808198k

  日期：——

  spacer-technique to develop dendritic and polymeric self-immolative molecular systems that can disassemble through a domino-like mechanism upon a stimulus event. In this report, we study the disassembly of a system that can disintegrate through para- and ortho-azaquinone-methide eliminations. The disassembly was evaluated with molecules that undergo single 1,6- or 1,4-elimination and with molecules that

  消除氮杂醌是一个强大而有效的反应，可用于拆解前药系统中的间隔基。我们和其他人已经使用间隔子技术来开发树突状和聚合的自消灭分子系统，这些系统可以在刺激事件发生时通过类似多米诺的机制进行分解。在本报告中，我们研究了可通过对位和邻位氮杂醌甲基化物消除而分解的系统的分解。用经历单个1,6-或1,4-消除的分子和经历双重1,6-和1,4-消除的分子评估拆卸。在生理条件下，1,6-消除比1,4-消除略快。这项研究揭示了前药系统的拆卸行为。