2-甲基-4-(3-(甲硫基)苯基)丁-3-炔-2-醇 | 124153-80-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 2-甲基-4-(3-(甲硫基)苯基)丁-3-炔-2-醇
• 英文名称: 2-methyl-4-(3-(methylthio)phenyl)but-3-yn-2-ol
• 英文别名: 2-Methyl-4-(3-methylsulfanyl-phenyl)-but-3-yn-2-ol；2-methyl-4-(3-methylsulfanylphenyl)but-3-yn-2-ol
• CAS: 124153-80-6
• 化学式: C₁₂H₁₄OS
• 分子量: 206.309
• InChiKey: HZWNYJMWQOQKQR-UHFFFAOYSA-N

物化性质

• 沸点：
  333.1±27.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-甲基-4-(3-(甲硫基)苯基)丁-3-炔-2-醇 在 sodium hydride 作用下， 以 苯 为溶剂， 反应 1.0h， 以79%的产率得到1-乙炔基-3-(甲硫基)苯
  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
• 作为产物：
  描述：

  苯乙炔 在 正丁基锂 、 potassium tert-butylate 作用下， 反应 2.17h， 生成 2-甲基-4-(3-(甲硫基)苯基)丁-3-炔-2-醇
  参考文献：
  名称：

  Experimental and theoretical study of the dimetalation of phenylacetylene and (1-naphthyl)acetylene

  摘要：

  DOI：

  10.1021/jo00291a041

文献信息

• KLUSENER, PETER A. A.;HANEKAMP, JAAP C.;BRANDSMA, LAMBERT;VON, RAGUE SCHL+, J. ORG. CHEM., 55,(1990) N, C. 1311-1321
  作者：KLUSENER, PETER A. A.、HANEKAMP, JAAP C.、BRANDSMA, LAMBERT、VON, RAGUE SCHL+

  DOI：——

  日期：——
• Experimental and theoretical study of the dimetalation of phenylacetylene and (1-naphthyl)acetylene
  作者：Peter A. A. Klusener、Jaap C. Hanekamp、Lambert Brandsma、Paul v. R. Schleyer

  DOI：10.1021/jo00291a041

  日期：1990.2
• 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.