3-(4-methylsulfanylphenyl)-1-(4-fluorophenyl)prop-2-yn-1-one | 742699-40-7

• 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-methylsulfanylphenyl)-1-(4-fluorophenyl)prop-2-yn-1-one
• 英文别名: 1-(4-fluorophenyl)-3-(4-(methylthio)phenyl)prop-2-yn-1-one；1-(4-Fluorophenyl)-3-(4-methylsulfanylphenyl)prop-2-yn-1-one
• CAS: 742699-40-7
• 化学式: C₁₆H₁₁FOS
• 分子量: 270.327
• InChiKey: GWPXMTHGTIVQIP-UHFFFAOYSA-N

物化性质

• 熔点：
  99-100 °C
• 沸点：
  410.0±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 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：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-methylsulfanylphenyl)-1-(4-fluorophenyl)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 6-(4-Fluoro-phenyl)-4-(4-methanesulfonyl-phenyl)-3-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：

  4-溴茴香硫醚 在 manganese(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 正丁基锂 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 、 苯 为溶剂， 反应 7.05h， 生成 3-(4-methylsulfanylphenyl)-1-(4-fluorophenyl)prop-2-yn-1-one
  参考文献：
  名称：

  1,3-二芳基丙-2-yn-1-ones的合成及其与构效关系的研究：环氧合酶和脂氧合酶的双重抑制剂。

  摘要：

  设计，合成和评估了一组具有C-3 p-SO2Me COX-2药效基团的1,3-二芳基丙-2-yn-1-ones（13、17、23、26和27），作为潜在的双重抑制剂环氧合酶1/2（COX-1 / 2）和5 / 15-脂氧合酶（5 / 15-LOX）具有体内抗炎和镇痛作用。在这类化合物中，3-（4-甲磺酰基苯基）-1-（4-氟苯基）丙-2-炔-1-酮（13h）被确定为有效和选择性的COX-2抑制剂（COX-2 IC50 = 0.1 microM； SI = 300），效力比罗非昔布高5倍（COX-2 IC50 = 0.5 microM； SI> 200）。在大鼠角叉菜胶诱导的爪水肿测定中，口服30 mg / kg剂量后3 h，13h表现出中等的抗炎活性（炎症抑制26％）。相关的双重COX-1 / 2和5 / 15-LOX抑制剂3-（4-甲磺酰基苯基）-1-（4-氰基苯基）丙-2-炔-1-酮（13g，COX-1

  DOI：

  10.1021/jm0510474

文献信息

• Palladium-Catalyzed Difluorocarbene Transfer Enabled Divergent Synthesis of γ-Butenolides and Ynones from Iodobenzene and Terminal Alkynes
  作者：Heyun Sheng、Zhiwei Chen、Qiuling Song

  DOI：10.1021/jacs.3c13044

  日期：2024.1.17

  Herein, we report a ligand-controlled palladium-catalyzed method that enables the synthesis of ynones and γ-butenolides with excellent regioselectivity from the same set of readily available aryl iodides, aryl acetylenes, and BrCF2CO2K. In this reaction, the [PdII]═CF2 does demonstrate electrophilicity and can generate CO readily when reacting with H2O. It is environmentally friendly and safe compared

  在此，我们报道了一种配体控制的钯催化方法，该方法能够从同一组容易获得的芳基碘化物、芳基乙炔和 BrCF 2 CO 2 K 合成具有优异区域选择性的炔酮和 γ-丁烯内酯。在该反应中， [Pd II ]=CF 2确实表现出亲电性，与 H 2 O 反应时很容易生成 CO。与传统方法相比，它对环境友好且安全，并且当前的方案使我们能够以高产率提供炔酮和 γ-丁烯内酯出色的功能容差。此外，利用该策略还可以与相应的酚和醇获得酯。生物活性化合物后期功能化的成功进一步说明了该方案在材料开发和药物发现中的合成效用。
• Synthesis and biological evaluation of 1,3-diphenylprop-2-yn-1-ones as dual inhibitors of cyclooxygenases and lipoxygenases
  作者：P.N. Praveen Rao、Qiao-Hong Chen、Edward E. Knaus

  DOI：10.1016/j.bmcl.2005.07.036

  日期：2005.11

  A new class of 1,3-diphenylprop-2-yn-1-ones possessing a P-MeSO2 COX-2 phamacophore on the C-3 phenyl ring was designed for evaluation as dual inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX). Among the group of compounds evaluated, 1-(4-fluorophenyl)-3-(4-methanesulfonylphenyl)prop-2-yn-1-one (11j) exhibited excellent COX-2 inhibitory potency (COX-2 IC50 = 0.1 mu M) and selectivity (SI = 300), whereas 1-(4-eyanophenyl)-3-(4-methanesulfonylphenyl)prop-2-yn-1-one (11d) exhibited an optimal combination of COX and LOX inhibition (COX-2 IC50 = 1.0 mu M; COX-2 SI = 31.5; 5-LOX IC50 = 1 -0 mu M; 15-LOX IC50 = 3.2 mu M). (c) 2005 Elsevier Ltd. All rights reserved.