4-[2'-(N-t-butoxycarbonyl)aminoethyl]phenoxyacetic acid, methyl ester | 254750-55-5

• 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: 4-[2'-(N-t-butoxycarbonyl)aminoethyl]phenoxyacetic acid, methyl ester
• 英文别名: Methyl 2-[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]phenoxy]acetate
• CAS: 254750-55-5
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: TUSIDNKDPCILTI-UHFFFAOYSA-N

物化性质

• 沸点：
  436.7±30.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[2'-(N-t-butoxycarbonyl)aminoethyl]phenoxyacetic acid, methyl ester 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成 2-((4-methoxybenzyl)(2-((4-(2-(methylamino)-2-oxoethoxy)phenethyl)amino)-2-oxoethyl)amino)-N-methyl-N-((1R,2S)-1-phenyl-1-(prop-2-yn-1-yloxy)propan-2-yl)acetamide
  参考文献：
  名称：

  Comparison of diffusion coefficients for matched pairs of macrocyclic and linear molecules over a drug-like molecular weight range

  摘要：

  通过核磁共振波谱法比较了一系列紧密匹配的大环和线性分子对的扩散系数。大环系列的设计既与通常用于类药物分子的分子量范围重叠，又有所扩展。每个线性分子代表了其相应大环分子的碳解裂变，旨在最小化功能和物理化学性质的差异。每个分子系列均采用铜催化的叠氮-炔环加成（CuAAC）反应，在流动体系中使用铜管进行制备。在整个研究分子量范围内，大环系列始终展现出更高的扩散性。大环和线性类似物之间扩散系数的倍数差异似乎与溶剂粘度或介电环境无关。

  DOI：

  10.1039/c1ob05996c
• 作为产物：
  描述：

  对羟基苯乙腈 在 sodium tetrahydroborate 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[2'-(N-t-butoxycarbonyl)aminoethyl]phenoxyacetic acid, methyl ester
  参考文献：
  名称：

  Structure–activity relationship studies of a bisbenzimidazole-based, Zn2+-dependent inhibitor of HCV NS3 serine protease

  摘要：

  A survey of isosteric replacements of the phosphonoalanine side chain coupled with a process of conformational constraint of a bisbenzimidazole-based, Zn2+-dependent inhibitor of hepatitis C virus (HCV) NS3 serine protease resulted in the identification of novel series of active compounds with extended side chains. However, Zn2+-dependent HCV NS3 inhibition was relatively insensitive to the structural variations examined but dependent on the presence of negatively charged functionality. This result was interpreted in the context of an initial electrostatic interaction between protease and inhibitor that is subsequently consolidated by Zn2+, with binding facilitated by the featureless active site and proximal regions of the HCV NS3 protein. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00457-7

文献信息

• Synthesis of 5-Iodo-1,2,3-triazole-Containing Macrocycles Using Copper Flow Reactor Technology
  作者：Andrew R. Bogdan、Keith James

  DOI：10.1021/ol201567s

  日期：2011.8.5

  A new macrocyclization strategy to synthesize 12- to 31-membered 5-iodo-1,2,3-triazole-containing macrocycles is described. The macrocycles have been generated using a simple and efficient copper-catalyzed cycloaddition in flow under environmentally friendly conditions. This methodology also permits the facile, regioselective synthesis of 1,4,5-trisubstituted-1,2,3-triazole-containing macrocyles using

  描述了一种新的大环合成策略，可以合成12到31元的含5-碘-1,1,2,3-三唑的大环。大环化合物是在环境友好的条件下使用简单有效的铜催化环加成反应生成的。该方法还允许使用钯催化的交叉偶联反应，容易地，区域选择性地合成含1,4,5-三取代-1,2,3-三唑的大环。
• (Substituted)acyl dipeptidyl inhibitors of the ICE/ced-3 family of cysteine proteases
  申请人：Idun Pharmaceuticals, Inc.

  公开号：US20030232788A1

  公开（公告）日：2003-12-18

  This invention is directed to novel (substituted)acyl dipeptidyl ICE/ced-3 family inhibitor compounds. The invention is also directed to pharmaceutical compositions containing these compounds, as well as the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, for the prevention of ischemic injury, and for the preservation of organs that are to undergo a transplantation procedure.

  这项发明涉及新型（取代）酰基二肽酶ICE/ced-3家族抑制剂化合物。该发明还涉及含有这些化合物的药物组合物，以及将这些组合物用于治疗患有炎症、自身免疫和神经退行性疾病的患者，预防缺血性损伤，并保护即将进行移植手术的器官。
• Development of selective FGFR1 degraders using a Rapid synthesis of proteolysis targeting Chimera (Rapid-TAC) platform
  作者：Le Guo、Jin Liu、Xueqing Nie、Taobo Wang、Zhi-xiong Ma、Dan Yin、Weiping Tang

  DOI：10.1016/j.bmcl.2022.128982

  日期：2022.11

  bottleneck for the development of PROTACs is the need to screen multiple parameters to create an effective degrader. It often involves the synthesis of dozens to hundreds of compounds one by one through a tedious process. We have developed a two-stage approach that allows for the rapid synthesis of PROTACs (Rapid-TAC) using preassembled building blocks to screen multiple parameters simultaneously. We

  蛋白水解靶向嵌合体 (PROTAC) 已成为一种新型治疗策略。PROTAC 开发的主要瓶颈是需要筛选多个参数以创建有效的降解剂。它往往需要通过繁琐的过程，一个一个地合成几十到上百种化合物。我们开发了一种两阶段方法，允许使用预组装构建块同时筛选多个参数来快速合成 PROTAC (Rapid-TAC)。我们在此报告了这种方法在 FGFR（一种具有挑战性的膜蛋白靶标）的 PROTAC 开发中的应用。在第一阶段，我们从含酰肼的 FGFR 抑制剂和我们之前报道的带有各种接头和醛基官能团的 VHL 和 CRBN 配体库中快速制备了 24 种潜在的 PROTAC。然后将这 24 个 PROTAC 直接用于蛋白质降解细胞测定中的筛选。从最初的筛选中确定了多个命中。然后我们通过在第二阶段用酰胺替换水解不稳定的酰腙基序来制备相应的稳定类似物。其中，PROTACLG1188被确定为一种有效的选择性 FGFR1 降解剂。
• METHODS OF TREATING ALZHEIMER'S DISEASE
  申请人：Hook Gregory

  公开号：US20100216875A1

  公开（公告）日：2010-08-26

  The invention is directed to a method of treating Alzheimer's disease. The method comprises administering a cysteine protease inhibitor to a patient and thereby affecting the disease. In a preferred method, the cysteine protease inhibitor is a cathepsin B inhibitor. A preferred method causes a reversal in the progression of the Alzheimer's disease, especially an improvement in cognitive deficit. A preferred method also causes a reduction in Aβ. The method includes using a reversible or irreversible cysteine protease inhibitor or a combination thereof.
• [EN] METHODS OF TREATING ALZHEIMER'S DISEASE<br/>[FR] PROCÉDÉS DE TRAITEMENT DE MALADIE D'ALZHEIMER
  申请人：HOOK GREGORY

  公开号：WO2008077109A1

  公开（公告）日：2008-06-26

  [EN] The invention is directed to a method of treating Alzheimer's disease. The method comprises administering a cysteine protease inhibitor to a patient and thereby affecting the disease. In a preferred method, the cysteine protease inhibitor is a cathepsin B inhibitor. A preferred method causes a reversal in the progression of the Alzheimer's disease, especially an improvement in cognitive deficit. A preferred method also causes a reduction in Aß. The method includes using a reversible or irreversible cysteine protease inhibitor or a combination thereof.
  [FR] Procédé de traitement de maladie d'Alzheimer, comme suit: administration d'inhibiteur de cystéine protéase et action sur la maladie. En mode de réalisation préféré, l'inhibiteur est un inhibiteur de cathepsine B. Un tel mode de réalisation préféré permet d'inverse la progression de la maladie, et d'atténuer notamment le déficit cognitif, mais il entraîne aussi une réduction d'Aß. Le procédé décrit consiste à utiliser un inhibiteur de protéase cystéine réversible ou irréversible ou une combinaison correspondante.