4-methylsulfonamidophenacyl 4-methylphenylacetate | 919122-34-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methylsulfonamidophenacyl 4-methylphenylacetate
• 英文别名: [2-[4-(Methanesulfonamido)phenyl]-2-oxoethyl] 2-(4-methylphenyl)acetate
• CAS: 919122-34-2
• 化学式: C₁₈H₁₉NO₅S
• 分子量: 361.419
• InChiKey: IWMVUNDSZZXJSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-methylsulfonamidophenacyl 4-methylphenylacetate 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以42%的产率得到N-[4-(5-oxo-4-p-tolyl-2,5-dihydro-furan-3-yl)-phenyl]-methanesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity

  摘要：

  A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO2) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO2NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC50 > 100 mu M). These SAR,data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.023
• 作为产物：
  描述：

  N-(4-乙酰基苯基)甲磺酰胺 在 三氯化铝 、 溴 、 三乙胺 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 1.5h， 生成 4-methylsulfonamidophenacyl 4-methylphenylacetate
  参考文献：
  名称：

  Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity

  摘要：

  A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO2) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO2NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC50 > 100 mu M). These SAR,data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.023

文献信息

• Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity
  作者：Afshin Zarghi、P.N. Praveen Rao、Edward E. Knaus

  DOI：10.1016/j.bmc.2006.10.023

  日期：2007.1

  A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO2) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO2NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC50 > 100 mu M). These SAR,data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes. (c) 2006 Elsevier Ltd. All rights reserved.