p-(methylthio)heptanophenone | 699535-58-5

• 英文名称: p-(methylthio)heptanophenone
• 英文别名: 1-(4-Methylsulfanylphenyl)heptan-1-one
• CAS: 699535-58-5
• 化学式: C₁₄H₂₀OS
• 分子量: 236.378
• InChiKey: OHBDHKYVZKOMIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  p-(methylthio)heptanophenone 在 4 A molecular sieve 二氯二茂钛 、 Oxone 、 magnesium 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 30.0h， 生成 1-[(E)-1-hexyl-2-phenylvinyl]-4-(methylsulfonyl)benzene
  参考文献：
  名称：

  A new class of acyclic 2-alkyl-1,2-diaryl (E)-olefins as selective cyclooxygenase-2 (COX-2) inhibitors

  摘要：

  A new class of (E)-2-alkyl-2-(4-methanesulfonylphenyl)-1-phenylethenes were designed for evaluation as selective cyclooxygense-2 (COX-2) inhibitors. The target olefins were synthesized, via a Takeda olefination reaction, followed by oxidation of the respective thiomethyl olefinic intermediate. In vitro COX-1/COX-2 inhibition studies identified (E)-2-(4-methanesulfonylphenyl)-1-phenyloct-1-ene (8d) as a potent (IC50 = 0.77 muM) and selective (Selectivity Index > 130) COX-2 inhibitor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.027
• 作为产物：
  描述：

  茴香硫醚 、 庚酰氯 在 三氯化铝 作用下， 以 氯仿 为溶剂， 反应 1.5h， 以96%的产率得到p-(methylthio)heptanophenone
  参考文献：
  名称：

  Design and synthesis of acyclic triaryl (Z)-olefins: a novel class of cyclooxygenase-2 (COX-2) inhibitors

  摘要：

  A group of acyclic 2-alkyl-1, 1-diphenyl-2-(4-methylsulfonylphenyl)ethenes was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition structure-activity studies identified 1,1-diphenyl-2(4-methylsulfonylphenyl)hex-1-ene as a highly potent (IC50 = 0.014muM), and an extremely selective [COX-2 selectivity index (SI) >7142], COX-2 inhibitor that showed superior anti-inflammatory (A1) activity (ID50 = 2.5 mg/kg) relative to celecoxib (ID50 = 10.8mg/kg). This initial study was extended to include the design of a structurally related group of acyclic triaryl (Z)-olefins possessing an acetoxy (OAc) substituent at the para-position of the C-1 phenyl ring that is cis to a C-2 4-methylsulfonylphenyl substituent. COX-1 and COX-2 inhibition studies showed that (Z)-1-(4-acetoxyphenyl)-1-phenyl-2-(4-methylsulfonylphenyl)but-1-ene [(Z)-13b] is a potent (COX-1 IC50 = 2.4muM; COX-2 IC50 = 0.03 muM), and selective (COX-2 SI = 81), COX-2 inhibitor which is a potent AI agent (ID50 = 4.1 mg/kg) with equipotent analgesic activity to celecoxib. A molecular modeling (docking) study showed that the SO2Me substituent of (Z)-13b inserts deep inside the 2degrees-pocket of the COX-2 active site where one of the O-atoms of SO, group undergoes a H-bonding interaction with Phe(518). The p-OAc substituent on the C-1 phenyl ring is oriented in a hydrophobic pocket comprised of Met(522), Gly(526), Trp(387), Tyr(348), and Tyr(385), and the C-2 ethyl substituent is oriented towards the mouth of the COX-2 channel in the vicinity of amino acid residues Arg(12)0, Leu(531), and Val(349). Structure-activity data acquired indicate that a (Z)olefin having cis C-1 4-acetoxyphenyl (phenyl) and C-2 4-methylsulfonylphenyl substituents, and a C-1 phenyl substituent in conjunction with either a C-2 hydrogen or short alkyl substituent provides a novel template to design acyclic olefinic COX-2 inhibitors that, like aspirin, have the potential to acetylate COX-2. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.021

文献信息

• Methylsulfonyl and Hydroxyl Substituents Induce<i>Z</i>-Stereocontrol in the McMurry Olefination Reaction
  作者：Edward E. Knaus、Md. Jashim Uddin、P. N. Rao

  DOI：10.1055/s-2004-829087

  日期：——

  Aryl ketones possessing methylsulfonyl and hydroxyl substituents, that induce stereocontrol, selectively afford Z-olefins using a Zn-TiCl4 catalyzed McMurry reaction.

  具有甲基磺酰基和羟基取代基的芳基酮，能够引导立体控制，在Zn-TiCl4催化的McMurry反应中选择性地生成Z-烯烃。
• Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors
  作者：Md.Jashim Uddin、P. N. Praveen Rao、Edward E Knaus

  DOI：10.1016/j.bmcl.2004.01.075

  日期：2004.4

  A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone(, in 62-76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC50 = 0.014 muM) and selective COX-2 (Selectivity Index >7142) inhibitory activity. (C) 2004 Elsevier Ltd. All rights reserved.