4-(7'-octynoyl)-2,6-di-tert-butylphenol | 28441-00-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(7'-octynoyl)-2,6-di-tert-butylphenol
• 英文别名: 1-[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1-octanone；1-(3,5-ditert-butyl-4-hydroxyphenyl)octan-1-one
• CAS: 28441-00-1
• 化学式: C₂₂H₃₆O₂
• 分子量: 332.527
• InChiKey: KQJHOKXTCJAARZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(7'-octynoyl)-2,6-di-tert-butylphenol 在 四氯化钛 、 三乙胺 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 26.5h， 生成 (Z)-2-(3,5-di-tert-butyl-4-acetoxyphenyl)-1-(4-methylsulfonylphenyl)-1-phenylnon-1-ene
  参考文献：
  名称：

  Synthesis and biological evaluation of acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl pharmacophore: Dual inhibitors of cyclooxygenases and lipoxygenases

  摘要：

  A new class of regioisomeric acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) 5-lipoxygenase (5-LOX) pharmacophore that is vicinal to a para-methanesulfonylphenyl cyclooxygenase-2 (COX-2) pharmacophore were designed for evaluation as selective COX-2 and/or 5-LOX inhibitors. The target compounds were synthesized via a highly stereoselective McMurry olefination cross-coupling reaction. This key synthetic step afforded a (Z):(E) olefinic mixture with a predominance for the (Z)-olefin stereoisomer. Structure-activity studies for the (Z)-1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(4-methanesulfonylphenyl)-1-phenylalk-1-ene regioisomers showed that COX-1 inhibition decreased, COX-2 inhibition increased, and the COX-2 selectivity index (SI) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased (Et -> n-butyl -> n-heptyl). In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC50 = 0.3 mu M) and 15-LOX (IC50 = 0.8 mu M) relative to the inactive (IC50 > 10 mu M) Et and n-heptyl analogs. Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX (COX-1 IC50 = 3.0 mu M, and COX-2 IC50 = 0.36 mu M, COX-2 SI = 8.3) isozymes. A comparison of the relative inhibitory activities of the two groups of regioisomers investigated shows that the regioisomers in which the alkyl substituent is attached to the same olefinic carbon atom (C-2) as the para-methanesulfonylphenyl moiety generally exhibit a greater potency with respect to COX-2 inhibition. The 4-hydroxy substituent in the 3,5-di-tert-butyl-4-hydroxyphenyl moiety is essential for COX and LOX inhibition since 3,5-di-tert-butyl-4-acetoxyphenyl derivatives were inactive inhibitors. These structure-activity data indicate acyclic triaryl (Z)-olefins constitute a suitable template for the design of dual COX-2/LOX inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.054
• 作为产物：
  描述：

  2,6-二叔丁基苯酚 、 辛酰氯 在 三氯化铝 作用下， 以65%的产率得到4-(7'-octynoyl)-2,6-di-tert-butylphenol
  参考文献：
  名称：

  Sergovskaya, N. L.; Kornienko, N. I.; Shekhter, O. V., Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, # 10, p. 1910 - 1913

  摘要：

  DOI：

文献信息

• Sergovskaya, N. L.; Kornienko, N. I.; Shekhter, O. V., Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, # 10, p. 1910 - 1913
  作者：Sergovskaya, N. L.、Kornienko, N. I.、Shekhter, O. V.、Tsizin, Yu. S.

  DOI：——

  日期：——
• SERGOVSKAYA, N. L.;KORNIENKO, N. I.;SHEXTER, O. V.;TSIZIN, YU. S., ZH. ORGAN. XIMII, 1982, 18, N 10, 2167-2170
  作者：SERGOVSKAYA, N. L.、KORNIENKO, N. I.、SHEXTER, O. V.、TSIZIN, YU. S.

  DOI：——

  日期：——
• US7534539B2
  申请人：——

  公开号：US7534539B2

  公开（公告）日：2009-05-19
• Synthesis and biological evaluation of acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl pharmacophore: Dual inhibitors of cyclooxygenases and lipoxygenases
  作者：Anne Moreau、P.N. Praveen Rao、Edward E. Knaus

  DOI：10.1016/j.bmc.2006.03.054

  日期：2006.8

  A new class of regioisomeric acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) 5-lipoxygenase (5-LOX) pharmacophore that is vicinal to a para-methanesulfonylphenyl cyclooxygenase-2 (COX-2) pharmacophore were designed for evaluation as selective COX-2 and/or 5-LOX inhibitors. The target compounds were synthesized via a highly stereoselective McMurry olefination cross-coupling reaction. This key synthetic step afforded a (Z):(E) olefinic mixture with a predominance for the (Z)-olefin stereoisomer. Structure-activity studies for the (Z)-1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(4-methanesulfonylphenyl)-1-phenylalk-1-ene regioisomers showed that COX-1 inhibition decreased, COX-2 inhibition increased, and the COX-2 selectivity index (SI) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased (Et -> n-butyl -> n-heptyl). In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC50 = 0.3 mu M) and 15-LOX (IC50 = 0.8 mu M) relative to the inactive (IC50 > 10 mu M) Et and n-heptyl analogs. Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX (COX-1 IC50 = 3.0 mu M, and COX-2 IC50 = 0.36 mu M, COX-2 SI = 8.3) isozymes. A comparison of the relative inhibitory activities of the two groups of regioisomers investigated shows that the regioisomers in which the alkyl substituent is attached to the same olefinic carbon atom (C-2) as the para-methanesulfonylphenyl moiety generally exhibit a greater potency with respect to COX-2 inhibition. The 4-hydroxy substituent in the 3,5-di-tert-butyl-4-hydroxyphenyl moiety is essential for COX and LOX inhibition since 3,5-di-tert-butyl-4-acetoxyphenyl derivatives were inactive inhibitors. These structure-activity data indicate acyclic triaryl (Z)-olefins constitute a suitable template for the design of dual COX-2/LOX inhibitors. (c) 2006 Elsevier Ltd. All rights reserved.