3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-one | 742699-31-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-one
• CAS: 742699-31-6
• 化学式: C₁₆H₁₁FO₂
• 分子量: 254.261
• InChiKey: UYQBZEPZLORRGG-UHFFFAOYSA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  387.5±52.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-one 在 Oxone 、 sodium hydride 作用下， 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 4-(4-Fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-6-(4-methoxy-phenyl)-pyran-2-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship Studies of 3,4,6-Triphenylpyran-2-ones as Selective Cyclooxygenase-2 Inhibitors

  摘要：

  A group of regioisomeric 3,4,6-triphenylpyran-2-ones with a MeSO2 pharmacophore at the paraposition of either a C-3 phenyl or a C-4 phenyl substituent on the central six-membered pyran-2-one ring were prepared and evaluated in vitro for their abilities to inhibit the isozymes COX-1 and COX-2. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position of the C-6 phenyl ring attached to the central pyranone, showed that 6-(4-methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was the most potent and selective COX-2 inhibitor (COX-2 IC50 = 0.02 muM; COX-1 IC50 > 100 muM) with a high COX-2 selectivity index (SI > 5000) relative to the reference drugs celecoxib (COX-2 IC50 = 0.07 muM; SI = 474) and rofecoxib (COX-2 IC50 = 0.50 muM; SI > 200). 6-(4-Methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (12e) was a more potent oral antiinflammatory agent (ID50 = 5.6 mg/kg) than celecoxib (ID50 = 10.8 mg/kg) in a carrageenan-induced rat paw edema assay. In a 4% NaCl-induced abdominal constriction assay, a 5 mg/kg oral dose of 12e exhibited good analgesic activity at different time intervals producing 37.5 and 69% inhibition of writhing at 30 and 60 min, respectively. In contrast, the corresponding 6-(4-methoxyphenyl)-4-(4-methanesulfonylphenyl)-3-phenylpyran-2-one regiosiomer (12o) was a less potent and selective COX-2 inhibitor (COX-2 IC50 = 0.45 muM; SI = 70). A molecular modeling study for 12e indicated that the p-OMe substituent on the C-6 phenyl ring interacts with the COX-2 binding site amino acids Ile(345), Val(349), Leu(359), Leu(531), and Met(535) and that the OMe substituent may be responsible for proper orientation of the C-3 p-SO2Me-phenyl ring within the COX-2 secondary pocket (Gln(192), Arg(513), and Phe(518)). These results show that the COX-2 selectivity and potency of 3,4,6-triphenylpyranone regioisomers can be modulated by appropriate placement of the p-SO2Me pharmacophore on either the C-3 or C-4 phenyl moiety. In addition, electronic properties at the para-position of a C-6 phenyl substituent on the central pyranone ring govern COX-2 inhibitory potency and selectivity by controlling the orientation of the p-SO2Me pharmacophore within the COX-2 secondary pocket.

  DOI：

  10.1021/jm049939b
• 作为产物：
  描述：

  3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-ol 在 manganese(IV) oxide 作用下， 以 四氢呋喃 为溶剂， 以88 %的产率得到3-(4-fluorophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-one
  参考文献：
  名称：

  rintodestran (G1T48) 的硒类似物作为有效的雌激素受体调节剂和下调剂

  摘要：

  靶向治疗是对抗癌症的现代方向之一。如今，选择性雌激素受体调节剂（SERM）和下调剂（SERD）被用作雌激素受体阳性（ER+）肿瘤的一线治疗方法。在此，我们报告了 7 种新型苯并硒吩的设计和合成，及其 ER-α 结合活性和细胞毒性。TR-FRET竞争性ER-α结合实验表明，( E )-3-(4-((6-羟基-2-(4-羟基苯甲酰基)苯并[ b ]硒酚-3-基)氧基)苯基)丙烯酸酸 ( 21b ) 是一种比广为人知的 SERM 药物雷洛昔芬 (IC 50 = 1.78 nM)更有效的 ER-α 结合剂 ( IC 50 = 0.44 nM)。此外，21b和其他获得的硒类似物对大鼠成肌细胞（H9C2）没有毒性，表明取代的苯并[ b ]硒酚是开发用于治疗 ER+ 癌症的 ER-α 调节剂和下调剂的前瞻性支架。

  DOI：

  10.1039/d3nj01739g

文献信息

• Carboxyboronate as a Versatile In Situ CO Surrogate in Palladium‐Catalyzed Carbonylative Transformations
  作者：Chieh‐Hung Tien、Alina Trofimova、Aleksandra Holownia、Branden S. Kwak、Reed T. Larson、Andrei K. Yudin

  DOI：10.1002/anie.202010211

  日期：2021.2.19

  highlighted in the palladium‐catalyzed aminocarbonylation, alkoxycarbonylation, carbonylative Sonogashira coupling, and carbonylative Suzuki–Miyaura coupling of aryl halides. A variety of amides, esters, (hetero)aromatic ynones, and bis(hetero)aryl ketones were synthesized in good‐to‐excellent yields in a one‐pot fashion.

  羧基-MIDA-硼酸酯的应用（MIDA = N-甲基亚氨基二乙酸）作为各种钯催化转化的原位CO替代物进行了描述。先前曾证明，羧基MIDA硼酸酯是合成硼酸化杂环化合物的长凳稳定的含硼结构单元。本研究表明，羧基-MIDA-硼酸酯除了可用作杂环合成的前体外，它还是一种出色的原位CO替代物，可耐受胺，醇和碳基亲核试剂等反应性功能。在钯催化的氨基羰基化，烷氧基羰基化，羰基化的Sonogashira偶联和芳基卤化物的羰基化的Suzuki-Miyaura偶联中，突出了其广泛的官能团相容性。各种酰胺，酯，（杂）芳族炔酮
• Tandem Aza Michael Addition–Vinylogous Nitroaldol Condensation: Construction of Highly Substituted <i>N</i>-Fused 3-Nitropyrazolopyridines
  作者：Owk Obulesu、V. Murugesh、Battu Harish、Surisetti Suresh

  DOI：10.1021/acs.joc.8b00746

  日期：2018.6.15

  A base-mediated tandem aza-Michael addition–vinylogous nitroaldol condensation has been described between 3,5-dialkyl 4-nitropyrazoles and alkynyl ketones/aldehydes. This transition metal-free atom economical transformation occurred via C–N and C═C bond formations in one step with the elimination of water. The construction of a variety of highly substituted N-fused 3-nitropyrazolopyridine derivatives

  3,5-二烷基4-硝基吡唑与炔基酮/醛之间存在碱介导的串联氮杂-迈克尔加成-乙烯基硝基醛缩合反应。这种无过渡金属的原子经济转变是通过消除水和一步形成C–N和C═C键而实现的。已经证明以高收率构建了多种高度取代的N-稠合的3-硝基吡唑并吡啶衍生物。用不对称取代的4-硝基吡唑已经实现了良好到优异的区域选择性。
• Synthesis of Iron Oxide Palladium Nanoparticles and Their Catalytic Applications for Direct Coupling of Acyl Chlorides with Alkynes
  作者：Rakesh K. Sharma、Manavi Yadav、Rashmi Gaur、Radhika Gupta、Alok Adholeya、Manoj B. Gawande

  DOI：10.1002/cplu.201600321

  日期：2016.12

  plasma, FTIR spectroscopy, vibrating sample magnetometry, and atomic absorption spectroscopy. This nanocatalyst can be magnetically recovered and reused in multiple runs without any noticeable loss in catalytic activity.

  合成了一种新的磁性的，基于二氧化硅的磁性钯纳米催化剂，并首次将其用于酰氯与末端炔烃的直接偶联，以制备各种炔酮。合成的纳米复合材料是出色的多相催化剂，可在室温下在有氧条件下通过Sonogashira反应形成无铜，无膦，CC键，而无需使用任何添加剂和惰性条件。合成的催化剂已通过多种技术进行了全面表征，例如XRD，SEM，TEM，能量色散X射线光谱法，X射线光电子能谱，感应耦合等离子体，FTIR光谱，振动样品磁法和原子吸收光谱。
• Carbonylative Sonogashira Coupling of Aryl Iodides with Terminal Alkynes Catalyzed by Palladium Nanoparticles
  作者：Xiujuan Feng、Jiliang Song、Ming Bao

  DOI：10.1002/jccs.201700302

  日期：2018.3

  synthesis of α,β‐alkynyl ketones from the three‐component coupling of aryl iodides, terminal alkynes, and carbon monoxide (carbonylative Sonogashira coupling reaction) is successfully developed. The carbonylative Sonogashira coupling reaction proceeded smoothly under mild conditions in the presence of palladium nanoparticles to produce the corresponding α,β‐alkynyl ketones in good to excellent yields.

  成功开发了一种由芳基碘化物，末端炔烃和一氧化碳的三组分偶合（羰基Sonogashira偶合反应）合成α，β-炔基酮的简便有效的方法。羰基Sonogashira偶联反应在钯纳米粒子存在的条件下在温和条件下平稳进行，可产生相应的α，β-炔基酮，收率良好。
• Functionalized Magnetic Mesoporous Silica Nanoparticle-Supported Palladium Catalysts for Carbonylative Sonogashira Coupling Reactions of Aryl Iodides
  作者：Suzana Natour、Raed Abu-Reziq

  DOI：10.1002/cctc.201500356

  日期：2015.7.13

  ligands, which provided coordination sites for conjugation with a palladium catalyst. These modified particles were fully characterized and employed as catalyst nanosupports. The palladium catalyst was immobilized on the surface and within the pores of MMSN and applied in copper‐free carbonylative Sonogashira coupling reactions of aryl iodides with terminal alkynes.

  制备了磁性介孔二氧化硅纳米粒子（MMSN），并将其用作钯催化剂的载体。表面积为1909 m 2  g -1的MMSN通过纳米乳化工艺合成，其中包括在十六烷基三甲基溴化铵存在下将疏水性磁铁矿纳米颗粒分散在氯仿中，然后添加四乙氧基硅烷并通过溶胶-凝胶途径进行缩聚。MMSN用膦和基于N-杂环卡宾的配体进行了修饰，这些配体提供了与钯催化剂结合的配位点。这些改性的颗粒被充分表征并用作催化剂纳米载体。钯催化剂固定在MMSN的表面和孔中，并用于芳基碘化物与末端炔烃的无铜羰基Sonogashira偶联反应。