4-[2-(2-Methylsulfonylphenyl)ethynyl]pyridine | 1019322-14-5

• 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-[2-(2-Methylsulfonylphenyl)ethynyl]pyridine
• CAS: 1019322-14-5
• 化学式: C₁₄H₁₁NO₂S
• 分子量: 257.313
• InChiKey: VNELCQYKANNPCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(2-(甲硫基)苯基)-2-(4-吡啶基)乙炔 在 Oxone 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以32%的产率得到4-[2-(2-Methylsulfonylphenyl)ethynyl]pyridine
  参考文献：
  名称：

  Synthesis and cyclooxygenase inhibitory activities of linear 1-(methanesulfonylphenyl or benzenesulfonamido)-2-(pyridyl)acetylene regioisomers

  摘要：

  A group of 1-(aminosulfonylphenyl and methylsulfonylphenyl)-2-(pyridyl) acetylene regioisomers were designed such that a COX-2 SO2NH2 pharmacophore was located at the para-position of the phenyl ring, or a SO2Me pharmacophore was placed at the ortho-, meta- or para-position of the phenyl ring, on an acetylene template (scaffold). The point of attachment of the pyridyl ring to the acetylene linker was simultaneously varied (2-pyridyl, 3-pyridyl, 4-pyridyl, 3-methyl- 2-pyridyl) to determine the combined effects of positional, steric, and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. These target linear 1-(phenyl)-2-(pyridyl) acetylenes were synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. Structure-activity relationship (SAR) data (IC50 values) acquired by determination of the in vitro ability of the title compounds to inhibit the COX-1 and COX-2 isozymes showed that the position of the COX-2 SO2NH2 or SO2Me pharmacophore on the phenyl ring, and the point of attachment of the pyridyl ring to the acetylene linker, were either individual, or collective, determinants of COX-2 inhibitory potency and selectivity. A number of compounds discovered in this study, particularly 1-(4-aminosulfonylphenyl)-2-(3-methyl-2-pyridyl) acetylene (22), 1-(3-methanesulfonylphenyl)-2-(2-pyridyl) acetylene (27), 1-(3methanesulfonylphenyl)-2-(4-pyridyl)acetylene (29), 1-(4-methanesulfonylphenyl)-2-(2-pyridyl)acetylene (30), and 1-(4-methanesulfonylphenyl)2-(3-pyridyl)acetylene (31), exhibit potent (IC50 = 0.04-0.33 mu M range) and selective (SI = 18 to > 312 range) COX-2 inhibitory activities, that compare favorably with the reference drug celecoxib (COX-2 IC50 = 0.07 mu M; COX-2 SI = 473). The sulfonamide (22), and methylsulfonyl (27 and 31), compounds exhibited anti-inflammatory activities (ID50 = 59.9-76.6 mg/kg range) that were intermediate in potency between the reference drugs aspirin (ID50 = 128.7 mg/kg) and celecoxib (ID50 = 10.8 mg/kg). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.003

文献信息

• Synthesis and cyclooxygenase inhibitory activities of linear 1-(methanesulfonylphenyl or benzenesulfonamido)-2-(pyridyl)acetylene regioisomers
  作者：Morshed Alam Chowdhury、Ying Dong、Qiao-Hong Chen、Khaled R.A. Abdellatif、Edward E. Knaus

  DOI：10.1016/j.bmc.2007.11.003

  日期：2008.2.15

  A group of 1-(aminosulfonylphenyl and methylsulfonylphenyl)-2-(pyridyl) acetylene regioisomers were designed such that a COX-2 SO2NH2 pharmacophore was located at the para-position of the phenyl ring, or a SO2Me pharmacophore was placed at the ortho-, meta- or para-position of the phenyl ring, on an acetylene template (scaffold). The point of attachment of the pyridyl ring to the acetylene linker was simultaneously varied (2-pyridyl, 3-pyridyl, 4-pyridyl, 3-methyl- 2-pyridyl) to determine the combined effects of positional, steric, and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. These target linear 1-(phenyl)-2-(pyridyl) acetylenes were synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. Structure-activity relationship (SAR) data (IC50 values) acquired by determination of the in vitro ability of the title compounds to inhibit the COX-1 and COX-2 isozymes showed that the position of the COX-2 SO2NH2 or SO2Me pharmacophore on the phenyl ring, and the point of attachment of the pyridyl ring to the acetylene linker, were either individual, or collective, determinants of COX-2 inhibitory potency and selectivity. A number of compounds discovered in this study, particularly 1-(4-aminosulfonylphenyl)-2-(3-methyl-2-pyridyl) acetylene (22), 1-(3-methanesulfonylphenyl)-2-(2-pyridyl) acetylene (27), 1-(3methanesulfonylphenyl)-2-(4-pyridyl)acetylene (29), 1-(4-methanesulfonylphenyl)-2-(2-pyridyl)acetylene (30), and 1-(4-methanesulfonylphenyl)2-(3-pyridyl)acetylene (31), exhibit potent (IC50 = 0.04-0.33 mu M range) and selective (SI = 18 to > 312 range) COX-2 inhibitory activities, that compare favorably with the reference drug celecoxib (COX-2 IC50 = 0.07 mu M; COX-2 SI = 473). The sulfonamide (22), and methylsulfonyl (27 and 31), compounds exhibited anti-inflammatory activities (ID50 = 59.9-76.6 mg/kg range) that were intermediate in potency between the reference drugs aspirin (ID50 = 128.7 mg/kg) and celecoxib (ID50 = 10.8 mg/kg). (c) 2007 Elsevier Ltd. All rights reserved.