3-(4-(tert-butoxy)phenyl)propanoic acid | 21323-98-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-(4-(tert-butoxy)phenyl)propanoic acid
• 英文别名: 3-(4-tert-butoxyphenyl)-propionic acid；3-(4-Tert-butoxyphenyl)propanoic acid；3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoic acid
• CAS: 21323-98-8
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: LRZTWGHLBQKZBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-(tert-butoxy)phenyl)propanoic acid 在 正丁基锂 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 5.17h， 生成 (2R)-2-(4-tert-butoxybenzyl)-N-(2,4-dimethoxybenzyl)-N-methylsuccinamic acid benzyl ester
  参考文献：
  名称：

  Calorimetric and Structural Studies of 1,2,3-Trisubstituted Cyclopropanes as Conformationally Constrained Peptide Inhibitors of Src SH2 Domain Binding

  摘要：

  Isothermal titration calorimetry and X-ray crystallography have been used to determine the structural and thermodynamic consequences associated with constraining the pTyr residue of the pYEE ligand for the Src Homology 2 domain of the Src kinase (Src SH2 domain). The conformation ally constrained peptide mimics that were used are cyclopropane-derived isosteres whereby a cyclopropane ring substitutes to the N-Ca-Cbeta atoms of the phosphotyrosine. Comparison of the thermodynamic data for the binding of the conformationally constrained peptide mimics relative to their equivalent flexible analogues as well as a native tetrapeptide revealed an entropic advantage of 5-9 cal mol(-1) K-1 for the binding of the conformationally constrained ligands. However, an unexpected drop in enthalpy for the binding of the conformationally constrained ligands relative to their flexible analogues was also observed. To evaluate whether these differences reflected conformational variations in peptide binding modes, we have determined the crystal structure of a complex of the Src SH2 domain bound to one of the conformationally constrained peptide mimics. Comparison of this new structure with that of the Src SH2 domain bound to a natural 11-mer peptide (Waksman et al. Cell 1993, 72, 779-790) revealed only very small differences. Hence, cyclopropane-derived peptides are excellent mimics of the bound state of their flexible analogues. However, a rigorous analysis of the structures and of the surface areas at the binding interface, and subsequent computational derivation of the energetic binding parameters, failed to predict the observed differences between the binding thermodynamics of the rigidified and flexible ligands, suggesting that the drop in enthalpy observed with the conformationally constrained peptide mimic arises from sources other than changes in buried surface areas, though the exact origin of the differences remains unclear.

  DOI：

  10.1021/ja011746f
• 作为产物：
  描述：

  3-[4-(Tert-butoxy)phenyl]prop-2-enoic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以4.29 g的产率得到3-(4-(tert-butoxy)phenyl)propanoic acid
  参考文献：
  名称：

  Design Strategies for the Sequence-Based Mimicry of Side-Chain Display in Protein β-Sheets by α/β-Peptides

  摘要：

  The sophistication of folding patterns and functions displayed by unnatural-backbone oligomers has increased tremendously in recent years. Design strategies for the mimicry of tertiary structures seem within reach; however, a general method for the mimicry of sheet segments in the context of a folded protein is an unmet need preventing realization of this goal. Previous work has shown that 1 -> 1 alpha ->beta-residue substitutions at cross-strand positions in a hairpin-forming alpha-peptide sequence can generate an alpha/beta-peptide analogue that folds in aqueous conditions but with a change in side-chain display relative to the natural sequence; this change would prevent application of single beta-residue substitutions in a larger protein. Here, we evaluate four different substitution strategies based on replacement of alpha alpha dipeptide segments for the ability to retain both sheet folding encoded by a parent alpha-peptide sequence as well as nativelike side-chain display in the vicinity of the beta-residue insertion point. High-resolution structure determination and thermodynamic analysis of folding by multidimensional NMR suggest that three of the four designs examined are applicable to larger proteins.

  DOI：

  10.1021/ja306311r

文献信息

• Inhibitor of ribonucleotide reductase of herpes viruses
  申请人：MERCK & CO. INC.

  公开号：EP0438873A1

  公开（公告）日：1991-07-31

  A series of substituted peptides have been found to possess antiviral potency - specifically against herpes viruses - by selectively inhibiting the viral ribonucleotide reductase enzyme.

  一系列替代肽已被发现具有抗病毒活性，特别针对疱疹病毒，通过选择性抑制病毒核糖核酸还原酶酶来实现。
• Modulating the selectivity of matriptase-2 inhibitors with unnatural amino acids
  作者：Catherine St-Georges、Antoine Désilets、François Béliveau、Mariana Ghinet、Sébastien P. Dion、Éloic Colombo、Pierre-Luc Boudreault、Rafael J. Najmanovich、Richard Leduc、Éric Marsault

  DOI：10.1016/j.ejmech.2017.02.006

  日期：2017.3

  homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase. Careful modifications of the P4, P3 and P2 positions with the help of unnatural amino acids led to a thorough understanding of Structure-Activity Relationship and a >60-fold increase in selectivity for matriptase-2 vs matriptase. Additionally, the introduction

  Matriptase-2是一种II型跨膜丝氨酸蛋白酶（TTSP），在肝脏中表达，并通过裂解血ju素来调节铁稳态。Matriptase-2成为治疗与铁超负荷有关的疾病（如血色素沉着症或β地中海贫血）的有吸引力的靶标。从其最接近的同源matriptase的晶体结构开始，我们构建了matriptase-2的同源性模型，以进一步优化丝氨酸诱捕肽模拟物抑制剂对matriptase-2相对于matriptase的选择性。在非天然氨基酸的帮助下，对P4，P3和P2位置的仔细修饰导致对结构-活性关系的透彻了解，并使matriptase-2相对于matriptase的选择性增加了> 60倍。此外，引入非天然氨基酸导致血浆稳定性显着提高。此类化合物代表了在铁超负荷的情况下测试matriptase-2抑制作用的有用药理学工具。
• [EN] FIBROBLAST ACTIVATION PROTEIN (FAP)-TARGETED IMAGING AND THERAPY OF CANCERS AND OTHER FIBROTIC AND INFLAMMATORY DISEASES<br/>[FR] IMAGERIE CIBLÉE DE PROTÉINE D'ACTIVATION DES FIBROBLASTES (FAP) ET THÉRAPIE DE CANCERS ET D'AUTRES MALADIES FIBROTIQUES ET INFLAMMATOIRES
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2021055641A1

  公开（公告）日：2021-03-25

  Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.

  纤维母细胞活化蛋白（FAP）靶向化合物（例如，共轭物）；一种用于影像癌症或纤维化的方法；以及治疗炎症性疾病/紊乱和癌症的方法。
• Phlorethyl-.beta.-alanyl-secretine
  申请人：Max-Planch-Gesellschaft zur Forderung der Wissenschaften

  公开号：US04167508A1

  公开（公告）日：1979-09-11

  A radioiodinated phloretyl-.beta.-alanyl-secretin, its salts and its protected derivatives. A process for the manufacture of a radioiodinated phloretyl-.beta.-alanyl-secretin and/or a salt thereof which process involves reacting phloretyl-.beta.-alanyl-secretin and/or a salt thereof with radioactive iodine. Phloretyl-.alpha.-alanyl-secretin, its salts and its protected derivatives. A method for the determination of secretin in a sample, which involves; mixing the sample with a known amount of a radioiodinated phloretyl-.beta.-alanyl-secretin and an antibody specific for secretin; measuring the degree of binding of the labelled radioiodinated phloretyl-.beta.-alanyl-secretin; and determining the amount of secretin present in the sample by comparing the degree of binding with a standard curve which has been obtained by adding known amounts of secretin to a defined mixture of the radioiodinated phloretyl-.beta.-alanyl-secretin and the antibody and determining the degree of binding for this known amount of secretin.

  一种放射性碘标记的芬乐酰-β-丙氨酰-胃泌素及其盐和保护衍生物。制造放射性碘标记的芬乐酰-β-丙氨酰-胃泌素和/或其盐的方法包括将芬乐酰-β-丙氨酰-胃泌素和/或其盐与放射性碘反应。芬乐酰-α-丙氨酰-胃泌素及其盐和保护衍生物。一种用于测定样品中胃泌素的方法，包括将样品与已知量的放射性碘标记的芬乐酰-β-丙氨酰-胃泌素和特异性抗体混合；测量标记的放射性碘标记的芬乐酰-β-丙氨酰-胃泌素的结合程度；通过比较结合程度与标准曲线来确定样品中胃泌素的量，该标准曲线是通过向定义的混合物中加入已知量的胃泌素，并确定该已知量的胃泌素的结合程度来获得的，该混合物包括放射性碘标记的芬乐酰-β-丙氨酰-胃泌素和抗体。
• [EN] ALPHA HELIX MIMETICS IN THE TREATMENT OF CANCER<br/>[FR] MIMÉTIQUES D'HÉLICE ALPHA DANS LE TRAITEMENT DU CANCER
  申请人：PRISM BIOLAB CORP

  公开号：WO2010044485A1

  公开（公告）日：2010-04-22

  Alpha-helix mimetic structures and compounds represented by the formula (I) wherein the general formula and the definition of each symbol are as defined in the specification, a compound relating thereto, and methods relating thereto, are disclosed. Applications of these compounds in the treatment of medical conditions, e.g., cancer diseases, fibrotic diseases, and pharmaceutical compositions comprising the mimetics are further disclosed.

  本发明公开了代表公式(I)的α-螺旋拟态结构和化合物，其中一般公式和每个符号的定义如规范所定义，涉及该化合物的化合物和涉及该化合物的方法。还公开了这些化合物在治疗医学疾病（例如癌症，纤维化疾病）中的应用以及包含这些拟态体的制药组合物。