1-(4-(methylsulfonyl)phenyl)pentan-1-one | 812650-06-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(methylsulfonyl)phenyl)pentan-1-one
• 英文别名: 1-(4-Methylsulfonylphenyl)pentan-1-one；1-(4-methylsulfonylphenyl)pentan-1-one
• CAS: 812650-06-9
• 化学式: C₁₂H₁₆O₃S
• 分子量: 240.323
• InChiKey: UQFPNUQVHORBNP-UHFFFAOYSA-N

物化性质

• 熔点：
  85-87 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  412.7±37.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-(methylsulfonyl)phenyl)pentan-1-one 在 四氯化钛 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 4.0h， 生成
  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
• 作为产物：
  描述：

  4-methylthiopentanophenone 在 oxone 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 15.0h， 以86%的产率得到1-(4-(methylsulfonyl)phenyl)pentan-1-one
  参考文献：
  名称：

  一氧化氮释放选择性雌激素受体调节剂：一种改善治疗指数的双功能方法。

  摘要：

  在癌症治疗中使用选择性雌激素受体调节剂（SERM）时，必须考虑诸如内皮功能障碍的不良反应。雌激素以及因此的SERMs调节血管活性一氧化氮（•NO）的合成。我们假设双功能方法将SERMs的拮抗作用与靶向性•NO释放相结合可以减少血管副作用。我们合成了一系列的NO释放SERM（NO-SERM）和衍生自三芳基烯烃铅的相应SERM（在NO释放后）。化合物对ERβ具有拮抗活性（IC50（ERβ）= 0.2-2.7μM），但与ERα无相互作用。SERM 5d治疗可显着降低ERβ阳性乳腺癌和黑色素瘤细胞的生长。相应的NO-SERM 4d额外释放了•NO，从而减弱了这种抗增殖作用。此外，4d靶向释放•NO抵消了5d在正常血管组织细胞中的抗增殖作用。综上所述，可通过这种双功能方法改善SERM的治疗指数。

  DOI：

  10.1021/acs.jmedchem.9b00171

文献信息

• Triaryl (Z)-olefins suitable for radiolabeling with carbon-11 or fluorine-18 radionuclides for positron emission tomography imaging of cyclooxygenase-2 expression in pathological disease
  作者：Khaled R.A. Abdellatif、Carlos A. Velázquez、Zhangjian Huang、Morshed A. Chowdhury、Edward E. Knaus

  DOI：10.1016/j.bmcl.2010.06.155

  日期：2010.9

  A group of (Z)-1,1-diphenyl-2-(4-methylsulfonylphenyl) alk-1-enes were synthesized using methodologies that will allow incorporation of a [(11)C] OCH(3) substituent at the para-position of the C-1 phenyl ring, a [(11)C] SO(2)CH(3) substituent at the para-position of the C-2 phenyl ring, a [(18)F] OCH(2)CH(2)F substituent at the para-position of the C-1 phenyl ring, and a [(18)F] CH(2)CH(2)F substituent at the C-2 position of the olefinic bond. The [(11)C] and [(18)F] radiotracers are designed as potential radiopharmaceuticals to image cyclooxygenase-2 (COX-2) expression in any organ where COX-2 is upregulated. The COX-1/COX-2 inhibition data acquired suggest that compounds having a [(11)C] OMe or [(18)F] OCH(2)CH(2)F substituent at the para-position of the C-1 phenyl ring may be more suitable for imaging COX-2 expression in view of their ability to exclusively inhibit the COX-2 isozyme. (C) 2010 Elsevier Ltd. All rights reserved.
• 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.
• Design and synthesis of acyclic triaryl (Z)-olefins: a novel class of cyclooxygenase-2 (COX-2) inhibitors
  作者：Md. Jashim Uddin、P.N. Praveen Rao、Edward E. Knaus

  DOI：10.1016/j.bmc.2004.08.021

  日期：2004.11

  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.
• Nitric Oxide-Releasing Selective Estrogen Receptor Modulators: A Bifunctional Approach to Improve the Therapeutic Index
  作者：Nicole Bechmann、Torsten Kniess、Jens Pietzsch

  DOI：10.1021/acs.jmedchem.9b00171

  日期：2019.7.25

  When using selective estrogen receptor modulators (SERMs) in cancer therapy, adverse effects such as endothelial dysfunction have to be considered. Estrogens and, consequently, SERMs regulate the synthesis of vasoactive nitric oxide (•NO). We hypothesized that a bifunctional approach combining the antagonistic action of SERMs with a targeted •NO release could diminish vascular side effects. We synthesized

  在癌症治疗中使用选择性雌激素受体调节剂（SERM）时，必须考虑诸如内皮功能障碍的不良反应。雌激素以及因此的SERMs调节血管活性一氧化氮（•NO）的合成。我们假设双功能方法将SERMs的拮抗作用与靶向性•NO释放相结合可以减少血管副作用。我们合成了一系列的NO释放SERM（NO-SERM）和衍生自三芳基烯烃铅的相应SERM（在NO释放后）。化合物对ERβ具有拮抗活性（IC50（ERβ）= 0.2-2.7μM），但与ERα无相互作用。SERM 5d治疗可显着降低ERβ阳性乳腺癌和黑色素瘤细胞的生长。相应的NO-SERM 4d额外释放了•NO，从而减弱了这种抗增殖作用。此外，4d靶向释放•NO抵消了5d在正常血管组织细胞中的抗增殖作用。综上所述，可通过这种双功能方法改善SERM的治疗指数。