4-(4-formylphenyl)butanoic acid | 34162-05-5

• 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-(4-formylphenyl)butanoic acid
• CAS: 34162-05-5
• 化学式: C₁₁H₁₂O₃
• 分子量: 192.214
• InChiKey: SJUVIKKCZJSMEU-UHFFFAOYSA-N

物化性质

• 沸点：
  369.8±17.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-formylphenyl)butanoic acid 在 咪唑 、 水 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 179.0h， 生成 2-[[4-[4-[[3-[(2-甲基-6-苯并噻唑基)氨基]-3-氧代丙基]氨基]-4-氧代丁基]苯基]甲基]丙二酸
  参考文献：
  名称：

  Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

  摘要：

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

  DOI：

  10.1021/jm201734r
• 作为产物：
  描述：

  4-苯基丁酸 在 lithium hydroxide monohydrate 、 硫酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 52.0h， 生成 4-(4-formylphenyl)butanoic acid
  参考文献：
  名称：

  Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

  摘要：

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

  DOI：

  10.1021/jm201734r

文献信息

• Ligand‐Controlled Regiodivergence in Nickel‐Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids**
  作者：Zi‐Qi Li、Yue Fu、Ruohan Deng、Van T. Tran、Yang Gao、Peng Liu、Keary M. Engle

  DOI：10.1002/anie.202010840

  日期：2020.12.14

  the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand‐free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti‐Markovnikov products can be accessed with a novel 4,4‐disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the

  据报道，镍催化的未活化链烯基羧酸的区域发散性氢芳基化和氢烯基化，从而金属中心周围的配体环境决定了区域化学结果。Markovnikov加氢官能化产物是在无配体的温和条件下获得的，产率高达99％，选择性> 20：1。另外，可以使用新型的4,4-二取代的Pyrox配体获得抗Markovnikov产物，并具有优异的收率和> 20：1的选择性。对配体的电子和空间效应都有助于高产率和选择性。机理研究表明，最佳配体引起的营业额限制和选择性决定步骤发生了变化。DFT计算表明，在反马尔科夫尼科夫途径中，
• Catalytic Aerobic Chemoselective α-Oxidation of Acylpyrazoles en Route to α-Hydroxy Acid Derivatives
  作者：Seiya Taninokuchi、Ryo Yazaki、Takashi Ohshima

  DOI：10.1021/acs.orglett.7b01293

  日期：2017.6.16

  described. Acylpyrazoles, carboxylic acid oxidation state substrates, were efficiently oxidized under aerobic conditions using TEMPO as an oxygenating agent. The mild catalytic conditions of the present catalysis were amenable to late-stage α-oxidation of various pharmaceutical agents and natural products, leading to previously unreported α-hydroxy acid derivatives in short steps. Preliminary mechanistic

  描述了酰基吡唑的催化有氧化学选择性α-氧化。使用TEMPO作为氧化剂，在好氧条件下可有效地氧化酰基吡唑类（羧酸的氧化态底物）。本催化的温和催化条件适合于各种药物和天然产物的后期α-氧化，从而在短时间内导致先前未报道的α-羟基酸衍生物。初步的机理研究表明，原位生成的过氧化铜（II）可作为路易斯酸/布朗斯台德碱协同催化剂。
• Artificial Protein Crosstalk with a Molecule that Exchanges Binding Partners
  作者：Ohad Suss、Olga Halfin、Ziv Porat、Yael Fridmann Sirkis、Leila Motiei、David Margulies

  DOI：10.1002/anie.202312461

  日期：2024.2.12

  Drawing inspiration from allosteric signaling enzymes, whose catalytic and regulatory units are non‐covalently linked, we have devised a method to establish unnatural, effector‐mediated enzyme activation within native cells. The feasibility of this approach is demonstrated by introducing a synthetic regulatory unit (sRU) onto glycogen synthase kinase 3 (GSK‐3) through non‐covalent means. Our study reveals that this synthetic regulator mediates an unnatural crosstalk between GSK‐3 and lactate dehydrogenase A (LDHA), whose expression is regulated by cellular oxygen levels. Specifically, with this approach, the constitutively active GSK‐3 is transformed into an activable enzyme, whereas LDHA is repurposed as an unnatural effector protein that controls the activity of the kinase, making it unnaturally dependent on the cell‘s hypoxic response. These findings demonstrate a step toward imitating the function of effector‐regulated cell‐signaling enzymes, which play a key biological role in mediating the response of cells to changes in their environment. In addition, at the proof‐of‐principle level, our results indicate the potential to develop a new class of protein inhibitors whose inhibitory effect in cells is dictated by the cell‘s environment and consequent protein expression profile.

  摘要从异位信号酶（其催化和调控单元是非共价连接的）中汲取灵感，我们设计了一种在原生细胞内建立非自然的、效应器介导的酶激活的方法。通过非共价方式在糖原合酶激酶 3（GSK-3）上引入合成调控单元（sRU），证明了这种方法的可行性。我们的研究发现，这种合成调节因子介导了 GSK-3 与乳酸脱氢酶 A（LDHA）之间的非自然串扰，而后者的表达受细胞氧水平的调节。具体来说，通过这种方法，组成型活性 GSK-3 被转化为一种可激活的酶，而 LDHA 则被改造为一种非天然的效应蛋白，可控制激酶的活性，从而使其不自然地依赖于细胞的缺氧反应。这些发现表明，在模仿效应器调控的细胞信号酶的功能方面迈出了一步，这种酶在介导细胞对环境变化的反应方面发挥着关键的生物学作用。此外，在原理验证层面，我们的研究结果表明有可能开发出一类新的蛋白质抑制剂，其对细胞的抑制作用取决于细胞的环境和随之而来的蛋白质表达谱。
• Method for pretreating and coating metal surfaces prior to forming, with a paint-like coating and use of substrates so coated
  申请人：——

  公开号：US20030185990A1

  公开（公告）日：2003-10-02

  The invention relates to a method for coating a metal strip for use in the automotive, aircraft or aerospace industry. The strip or the strip sections produced on the basis thereof in a later step is/are first coated with at least one anticorrosive coating and then with at least one coating of a paint-like polymer-containing coating. The strip, once coated with at least one anticorrosive coating or once coated with at least one coat of a paint-like coating, is divided up in strip sections. Said coated strip sections are then formed, joined and/or coated with at least one (further) paint-like coating and/or coat of paint. The paint-like coating is achieved by coating the surface with an aqueous dispersion that contains, in addition to water, at least one UV-crosslinkable water-soluble and/or water-dispersible resin, at least one wax as the forming additive, at least one photoinitiator, and at least one corrosion inhibitor. The coating is dried and cured once it has been applied to the metal surface, thereby forming a coating that has a thickness of up to 10 &mgr;m once cured.

  本发明涉及一种用于汽车、飞机或航空航天工业的金属带材涂层方法。在后面的步骤中，带材或在其基础上生产的带材部分首先涂上至少一层防腐涂层，然后涂上至少一层含漆聚合物涂层。涂有至少一层防腐涂层或至少一层类涂料涂层的带材被分割成带材段。然后，将涂有涂层的带材段成型、连接和/或涂覆至少一层（进一步的）类油漆涂层和/或油漆层。仿油漆涂层是通过在表面涂上水性分散体来实现的，该分散体除水之外，还含有至少一种可紫外线交联的水溶性和/或水分散性树脂、至少一种作为成型添加剂的蜡、至少一种光引发剂和至少一种腐蚀抑制剂。涂层涂抹到金属表面后进行干燥和固化，从而形成固化后厚度达 10 微米的涂层。
• Design, synthesis, and structure–activity relationships of a series of 4-benzyl-5-isopropyl-1H-pyrazol-3-yl β-d-glycopyranosides substituted with novel hydrophilic groups as highly potent inhibitors of sodium glucose co-transporter 1 (SGLT1)
  作者：Nobuhiko Fushimi、Hirotaka Teranishi、Kazuo Shimizu、Shigeru Yonekubo、Kohsuke Ohno、Takashi Miyagi、Fumiaki Itoh、Toshihide Shibazaki、Masaki Tomae、Yukiko Ishikawa-Takemura、Takeshi Nakabayashi、Noboru Kamada、Yuji Yamauchi、Susumu Kobayashi、Masayuki Isaji

  DOI：10.1016/j.bmc.2012.11.041

  日期：2013.2

  Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of therapeutic options for postprandial hyperglycemia. Previously, we reported potent and selective SGLT1 inhibitors 1 and 2 showing efficacy in oral carbohydrate tolerance tests in diabetic rat models. In a pharmacokinetic (PK) study of 2, excessive systemic exposure to metabolites of 2 was observed, presumably due to the high permeability of its aglycone (2a). To further improve SGLT1 inhibitory activity and reduce aglycone permeability, a series of 4-benzyl-5-isopropyl-1H-pyrazol-3-yl beta-D-glycopyranoside derivatives bearing novel hydrophilic substitution groups on the phenyl ring were synthesized and their inhibitory activity toward SGLTs was evaluated. Optimized compound 14c showed an improved profile satisfying both higher activity and lower permeability of its aglycone (22f) compared with initial leads 1 and 2. Moreover, the superior efficacy of 14c in various carbohydrate tolerance tests in diabetic rat models was confirmed compared with acarbose, an alpha-glucosidase inhibitor (alpha-GI) widely used in the clinic. (C) 2012 Elsevier Ltd. All rights reserved.