(E)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)hex-1-ene

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)hex-1-ene
• 化学式: C₂₅H₂₇NO₂S
• 分子量: 405.561
• InChiKey: QKOFJVGNHOACBX-OCOZRVBESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.21
• 重原子数：
  29.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.17
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  苯戊酮 在 四氯化钛 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.5h， 生成 (E)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)hex-1-ene
  参考文献：
  名称：

  Design and synthesis of (Z)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)alk-1-enes and (Z)-1-(4-azidophenyl)-1,2-diphenylalk-1-enes: novel inhibitors of cyclooxygenase-2 (COX-2) with anti-inflammatory and analgesic activity

  摘要：

  A group of novel (Z)-1,2-diphenyl-1-9(4-methanesulfonamidophenyl)alk-1-enes was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 enzyme inhibition studies identified (Z)-1,2-dipheny1-1-(4-methanesulfonamidophenyl)oct-1-ene(8d) as a highly potent (IC50=0.03 muM), and an extremely selective [COX-2 SI (selectivity index)> 3,333], COX-2 inhibitor that showed good anti-inflammatory (AI) activity (ID50 = 2.8 mg/kg). A molecular modeling (docking) study showed that the p-MeSO2NH group present in (Z)-8d inserts deep inside the 2degrees-pocket of the COX-2 binding site, it undergoes a hydrophobic interaction with Ala(516) and Gly(519), and one of the O-atoms of the MeSO2 group participates in a weak hydrogen bonding interaction with the NH2 of Arg(513) (distance = 3.85 Angstrom). Similar in vitro COX-1/COX-2 enzyme inhibition studies showed that the azido compound 1-(4-azidophenyl)-1,2-diphenyloct-1-ene (9c) is also a potent and selective COX-2 inhibitor (COX-2 IC50 = 0.11 muM: SI > 909) that exhibits good AI activity (ID50 = 5.0 mg/kg). A docking experiment to determine the orientation of (Z)-9c within the COX-2 binding site showed that the linear p-N-3 group inserts into the COX-2 2degrees-pocket, where it undergoes an ion-ion (electrostatic) interaction with Arg(513). Structure-activity data acquired indicate that an olefin having either a C-1 p-MeSO2NH-phenyl, or a p-N-3-phenyl, substituent, that is, cis to a C-2 unsubstituted phenyl substituent, in conjunction with C-1 unsubstituted phenyl and C-2 alkyl substituents, provides a novel template to design acyclic olefinic COX-2 inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.017

文献信息

• Design and synthesis of (Z)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)alk-1-enes and (Z)-1-(4-azidophenyl)-1,2-diphenylalk-1-enes: novel inhibitors of cyclooxygenase-2 (COX-2) with anti-inflammatory and analgesic activity
  作者：Md. Jashim Uddin、P.N. Praveen Rao、Edward E. Knaus

  DOI：10.1016/j.bmc.2004.10.017

  日期：2005.1

  A group of novel (Z)-1,2-diphenyl-1-9(4-methanesulfonamidophenyl)alk-1-enes was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 enzyme inhibition studies identified (Z)-1,2-dipheny1-1-(4-methanesulfonamidophenyl)oct-1-ene(8d) as a highly potent (IC50=0.03 muM), and an extremely selective [COX-2 SI (selectivity index)> 3,333], COX-2 inhibitor that showed good anti-inflammatory (AI) activity (ID50 = 2.8 mg/kg). A molecular modeling (docking) study showed that the p-MeSO2NH group present in (Z)-8d inserts deep inside the 2degrees-pocket of the COX-2 binding site, it undergoes a hydrophobic interaction with Ala(516) and Gly(519), and one of the O-atoms of the MeSO2 group participates in a weak hydrogen bonding interaction with the NH2 of Arg(513) (distance = 3.85 Angstrom). Similar in vitro COX-1/COX-2 enzyme inhibition studies showed that the azido compound 1-(4-azidophenyl)-1,2-diphenyloct-1-ene (9c) is also a potent and selective COX-2 inhibitor (COX-2 IC50 = 0.11 muM: SI > 909) that exhibits good AI activity (ID50 = 5.0 mg/kg). A docking experiment to determine the orientation of (Z)-9c within the COX-2 binding site showed that the linear p-N-3 group inserts into the COX-2 2degrees-pocket, where it undergoes an ion-ion (electrostatic) interaction with Arg(513). Structure-activity data acquired indicate that an olefin having either a C-1 p-MeSO2NH-phenyl, or a p-N-3-phenyl, substituent, that is, cis to a C-2 unsubstituted phenyl substituent, in conjunction with C-1 unsubstituted phenyl and C-2 alkyl substituents, provides a novel template to design acyclic olefinic COX-2 inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.