4-(4-fluorophenyl)-2,4-dioxobutanoic acid | 64393-83-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-fluorophenyl)-2,4-dioxobutanoic acid
• CAS: 64393-83-5
• 化学式: C₁₀H₇FO₄
• 分子量: 210.162
• InChiKey: SVVJJZMCLPHDOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  373.9±22.0 °C(Predicted)
• 密度：
  1.401±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-fluorophenyl)-2,4-dioxobutanoic acid 在 一水合肼 、 溶剂黄146 作用下， 以65%的产率得到3-(4-氟苯基)-1H-吡唑-5-甲酸
  参考文献：
  名称：

  5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII

  摘要：

  Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 mu M). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho-and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 mu M. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.052
• 作为产物：
  描述：

  4-(4-氟苯基)-2,4-二氧代丁酸乙酯 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以64%的产率得到4-(4-fluorophenyl)-2,4-dioxobutanoic acid
  参考文献：
  名称：

  [EN] SMALL MOLECULES FOR DISRUPTING THE SUPER ELONGATION COMPLEX AND INHIBITING TRANSCRIPTION ELONGATION FOR CANCER THERAPY
  [FR] PETITES MOLÉCULES PERMETTANT DE PERTURBER LE COMPLEXE DE SUPER-ALLONGEMENT ET D'INHIBER L'ALLONGEMENT DE LA TRANSCRIPTION POUR UNE CANCÉROTHÉRAPIE

  摘要：

  本文揭示了可用于抑制RNA聚合酶II（Pol II）转录的化合物，特别是破坏超级延伸复合物（SEC）的化合物。这些化合物可用于制备药物组合物和治疗与SEC生物活性相关的疾病和紊乱的方法，特别是与高水平表达SEC依赖基因相关的促进、支持或其他对疾病或紊乱必要的疾病和紊乱，如癌症。

  公开号：

  WO2019183373A1

文献信息

• Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and<i>in silico</i>studies
  作者：Pradeep K. Jaiswal、Vashundhra Sharma、Surendra Kumar、Manas Mathur、Ajit K. Swami、Dharmendra K. Yadav、Sandeep Chaudhary

  DOI：10.1002/ardp.201700349

  日期：2018.4

  A series of 2‐oxo‐2‐phenylethylidene linked 2‐oxo‐benzo[1,4]oxazine analogues 17a–x and 18a–o, incorporated with a variety of electron‐withdrawing as well as electron‐donating groups at ring A and ring C, were synthesized under greener conditions in excellent yields (up to 98%). These analogues 17a–x and 18a–o were evaluated for their arachidonic acid (AA)‐induced platelet aggregation inhibitory activities

  一系列 2-oxo-2-phenylethylidene 连接的 2-oxo-benzo[1,4]oxazine 类似物 17a-x 和 18a-o，在环 A 和环 C，在更环保的条件下以优异的产率（高达 98%）合成。与标准参考阿司匹林 (IC50 = 21.34 ± 1.09 µg/mL) 相比，评估了这些类似物 17a-x 和 18a-o 的花生四烯酸 (AA) 诱导的血小板聚集抑制活性。在所有筛选的化合物中，与阿司匹林相比，8 种类似物 17i、17x、18f、18g、18h、18i、18l 和 18o 被鉴定为有前途的血小板聚集抑制剂。此外，通过 MTT 分析对 3T3 成纤维细胞系进行了有希望的化合物（17i、17x、18f-18i、18l、和 18o) 并且发现这些化合物在性质上是无毒的。此外，这些化合物（17i、17x、18f-18i、18l 和 18o）的 AA 诱导的血
• COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS
  申请人：Kossen Karl

  公开号：US20090318455A1

  公开（公告）日：2009-12-24

  Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.

  公开了用于治疗炎症和纤维化疾病的化合物和方法，包括用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物对p38 MAPK的抑制效力较低；并且其中接触是在SAPK调节浓度下进行的，该浓度对化合物抑制p38 MAPK的抑制浓度百分比较低。还公开了吡非尼酮的衍生物和类似物，它们可用于调节应激活化蛋白激酶（SAPK）系统。
• [EN] ISOXAZOLE COMPOUNDS AND METHODS FOR THE TREATMENT OF CYSTIC FIBROSIS<br/>[FR] COMPOSÉS ISOXAZOLES ET PROCÉDÉS POUR LE TRAITEMENT DE LA FIBROSE KYSTIQUE
  申请人：FLATLEY DISCOVERY LAB

  公开号：WO2016054560A1

  公开（公告）日：2016-04-07

  The invention relates to a compound of Formula (I) and methods of treating cystic fibrosis comprising the step of administering a therapeutically effective amount of a compound of Formula (I) or II to a patient in need thereof: Formula (I) and Formula (II). The invention relates to the use of substituted oxazole and substituted thiazole compounds in the treatment of cystic fibrosis transmembrane conductance regulator (CFTR) mediated diseases.

  该发明涉及一种式（I）的化合物以及治疗囊性纤维化的方法，包括向需要的患者施用式（I）或II的化合物的治疗有效量：式（I）和式（II）。该发明涉及在治疗囊性纤维化跨膜传导调节蛋白（CFTR）介导的疾病中使用取代噁唑和取代噻唑化合物。
• “On water” ultrasound-assisted one pot efficient synthesis of functionalized 2-oxo-benzo[1,4]oxazines: First application to the synthesis of anticancer indole alkaloid, Cephalandole A
  作者：Pradeep K. Jaiswal、Vashundhra Sharma、Jaroslav Prikhodko、Irina V. Mashevskaya、Sandeep Chaudhary

  DOI：10.1016/j.tetlet.2017.03.048

  日期：2017.5

  For the first time, an efficient, simple, synthetic green protocol for the one-pot synthesis of functionalized 2-oxo-benzo[1,4]oxazines 24–29 in water under ultrasound irradiation is presented. As compared to conventional methods, the present protocol avoids traditional chromatography and purification steps and furnished the target molecules in excellent yields (upto 98%) with no side products. The

  对于第一次，一个高效，简便的，合成的绿协议的一锅合成官能-2-氧代苯并[1,4]恶嗪24 - 29在超声照射下的水被呈现。与常规方法相比，本方案避免了传统的色谱和纯化步骤，并以极高的收率（高达98％）提供了目标分子，且没有副产物。该方法也已在克级合成中得到证明。此外，官能化2-氧代-喹喔啉类似物31 - 33，另一类生物活性杂环支架的，使用这种方法，还制备。该方案首次成功地用于抗癌吲哚生物碱Cephalandole A的合成35。
• Furan-2,3-diones as masked dipoles: synthesis of isotetronic acids and mechanistic considerations
  作者：Vincent Barbier、François Couty、Olivier R.P. David

  DOI：10.1016/j.tet.2016.07.072

  日期：2016.9

  The formal dipolar behaviour of furan-2,3-diones is illustrated by their reaction with ethyl glyoxylate under Lewis basic activation uniquely, giving access to isotetronic derivatives. The Janus-type nature of the activated species, both nucleophilic and electrophilic is revealed by ring-opening of the starting ketolactone. An unexpected reversible side-reaction was identified by in situ monitoring

  呋喃-2,3-二酮的形式偶极行为可以通过在Lewis碱性活化下与乙醛酸乙酯的反应来唯一说明，从而获得了等电子衍生物。通过起始酮内酯的开环揭示了亲核和亲电子的活化物种的Janus型性质。通过原位监测发现意外的可逆反应。