dimethyl 2-<2-<4-(methylsulfonyl)phenyl>-2-oxoethyl>propanedioate | 173776-65-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: dimethyl 2-<2-<4-(methylsulfonyl)phenyl>-2-oxoethyl>propanedioate
• 英文别名: dimethyl 2-(2'-(4'-(methylsulfonyl)phenyl)-2'-oxoethyl)propane-1,3-dioate；Dimethyl {2-[4-(methylsulfonyl)-phenyl]-2-oxoethyl}malonate；dimethyl 2-[2-(4-methylsulfonylphenyl)-2-oxoethyl]propanedioate
• CAS: 173776-65-3
• 化学式: C₁₄H₁₆O₇S
• 分子量: 328.343
• InChiKey: IPQROFYLPCTTFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl 2-<2-<4-(methylsulfonyl)phenyl>-2-oxoethyl>propanedioate 在 吡啶 、 titanium(III) chloride 、 二异丁基氢化铝 、 potassium carbonate 、 potassium iodide 、 sodium iodide 、 锌 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 5-(4-methoxyphenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hept-5-ene
  参考文献：
  名称：

  Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors:  Synthesis and Structure−Activity Relationships

  摘要：

  A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the B-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity, Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.

  DOI：

  10.1021/jm950664x
• 作为产物：
  描述：

  对甲硫基苯甲腈 在 盐酸 、 溴 、 potassium carbonate 、 间氯过氧苯甲酸 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 8.5h， 生成 dimethyl 2-<2-<4-(methylsulfonyl)phenyl>-2-oxoethyl>propanedioate
  参考文献：
  名称：

  Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors:  Synthesis and Structure−Activity Relationships

  摘要：

  A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the B-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity, Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.

  DOI：

  10.1021/jm950664x

文献信息

• Efficient syntheses of 2-(3′,5′-difluorophenyl)-3-(4′-methylsulfonylphenyl)cyclopent-2-enone, a potent COX-2 inhibitor
  作者：Dalian Zhao、Feng Xu、Cheng-yi Chen、Rich D. Tillyer、Edward J.J. Grabowski、Paul J. Reider、Cameron Black、Nathalie Ouimet、Peppi Prasit

  DOI：10.1016/s0040-4020(99)00274-4

  日期：1999.5

  2-(3',5'-Difluorophenyl)-3-(4'-methylsulfonylphenyl)cyclopent-2-enone (1) displays high selectivity and potency against COX-2. Three efficient syntheses of this diarylcyclopentenone are described. The first approach employs a Suzuki coupling reaction as the key step while the second synthesis features an intramolecular Friedel-Crafts acylation. The third, and preferred route to this compound involves a sequential malonate alkylation and acylation and ring-closure sequence. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors:  Synthesis and Structure−Activity Relationships
  作者：Horng-Chih Huang、James J. Li、Danny J. Garland、Timothy S. Chamberlain、Emily J. Reinhard、Robert E. Manning、Karen Seibert、Carol M. Koboldt、Susan A. Gregory、Gary D. Anderson、Amy W. Veenhuizen、Yan Zhang、William E. Perkins、Earl G. Burton、J. Nita Cogburn、Peter C. Isakson、David B. Reitz

  DOI：10.1021/jm950664x

  日期：1996.1.1

  A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the B-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity, Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.