1-(4-Fluorophenyl)-2-[1-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]cyclobutan-1-yl]ethan-1-one | 171888-33-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-Fluorophenyl)-2-[1-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]cyclobutan-1-yl]ethan-1-one
• 英文别名: 1-(4-fluorophenyl)-2-[1-[2-(4-methylsulfonylphenyl)-2-oxoethyl]cyclobutyl]ethanone
• CAS: 171888-33-8
• 化学式: C₂₁H₂₁FO₄S
• 分子量: 388.46
• InChiKey: QMFBLTCYPHHFAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-Fluorophenyl)-2-[1-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]cyclobutan-1-yl]ethan-1-one 在 四氯化钛 、 锌 氮气 、 乙酸乙酯 、 水 、 Brine 、 magnesium sulfate 、 silica gel 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 16.75h， 以gave 13.5 g (76%) of 6-(4-fluorophenyl)-7-[4-(methylsulfonyl)phenyl]spiro[3.4]oct-6-ene as a colorless solid的产率得到6-(4-fluorophenyl)-7-[4-(methylsulfonyl)phenyl]spiro[3.4]oct-6-ene
  参考文献：
  名称：

  Substituted spiro compounds for the treatment of inflammation

  摘要：

  本文描述了一类取代螺环化合物，用于治疗炎症和炎症相关疾病。特别感兴趣的化合物由公式III定义：##STR1## 其中n是从0、1和2中选择的数字；其中R.sup.3是甲基磺酰基或磺酰胺基；其中R.sup.8从氢基、氟、氯、溴、碘、甲基、乙基、正丙基、异丙基、丁基、叔丁基、异丁基、甲氧基、乙氧基、丙氧基、丁氧基、羟基、巯基、甲硫基、乙硫基、氰基、氟甲基、二氟甲基、三氟甲基、氯甲基、二氯甲基、三氯甲基、五氟乙基、七氟丙基、二氟氯甲基、二氯氟甲基、二氟乙基、二氟丙基、二氯乙基、二氯丙基、三氟甲氧基、羟甲基、甲氧基甲基和乙氧基甲基；或其药学上可接受的盐。

  公开号：

  US05393790A1
• 作为产物：
  描述：

  对甲硫基苯甲腈 在 四氯化钛 、 三乙胺 、 间氯过氧苯甲酸 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 氯仿 为溶剂， 反应 7.33h， 生成 1-(4-Fluorophenyl)-2-[1-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]cyclobutan-1-yl]ethan-1-one
  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

• Substituted spiro compounds for the treatment of inflammation
  申请人：G.D. Searle & Co.

  公开号：US05393790A1

  公开（公告）日：1995-02-28

  A class of substituted spiro compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: ##STR1## wherein n is a number selected from 0, 1 and 2; wherein R.sup.3 is methylsulfonyl or sulfamyl; and wherein R.sup.8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; or a pharmaceutically-acceptable salt thereof.

  本文描述了一类取代螺环化合物，用于治疗炎症和炎症相关疾病。特别感兴趣的化合物由公式III定义：##STR1## 其中n是从0、1和2中选择的数字；其中R.sup.3是甲基磺酰基或磺酰胺基；其中R.sup.8从氢基、氟、氯、溴、碘、甲基、乙基、正丙基、异丙基、丁基、叔丁基、异丁基、甲氧基、乙氧基、丙氧基、丁氧基、羟基、巯基、甲硫基、乙硫基、氰基、氟甲基、二氟甲基、三氟甲基、氯甲基、二氯甲基、三氯甲基、五氟乙基、七氟丙基、二氟氯甲基、二氯氟甲基、二氟乙基、二氟丙基、二氯乙基、二氯丙基、三氟甲氧基、羟甲基、甲氧基甲基和乙氧基甲基；或其药学上可接受的盐。
• [EN] SUBSTITUTED SPIRO COMPOUNDS FOR THE TREATMENT OF INFLAMMATION<br/>[FR] COMPOSES SPIRANNIQUES SUBSTITUES UTILISES DANS LE TRAITEMENT DES INFLAMMATIONS
  申请人：G.D. SEARLE & CO.

  公开号：WO1995021817A1

  公开（公告）日：1995-08-17

  (EN) A class of substituted spiro compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (III), wherein n is a number selected from 0, 1 and 2; wherein R6 is selected from hydrido and halo; wherein R7 is selected from hydrido and halo; wherein R8 is selected from hydrido, halo, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, and hydroxyl; wherein R9 is selected from hydrido, halo, and lower alkyl; or wherein R8 and R9 together form methylenedioxy; and wherein R11 is selected from lower alkyl and amino; or a pharmaceutically-acceptable salt thereof.(FR) L'invention décrit une classe de composés spiranniques substitués utilisés dans le traitement des inflammations et des troubles inflammatoires. Les composés d'un intérêt particulier sont définis par la formule (III), dans laquelle n est un nombre sélectionné parmi 0, 1 et 2; R6 est sélectionné parmi hydrido et halo; R7 est sélectionné parmi hydrido et halo; R8 est sélectionné parmi hydrido, halo, alkyle inférieur, alcoxy inférieur, haloalkyle inférieur, haloalcoxy inférieur et hydroxyle; R9 est sélectionné parmi hydride, halo et alkyle inférieur ou R8 et R9 forment ensemble le méthylènedioxy; et R11 est sélectionné parmi alkyle inférieur et amino; ou un sel pharmaceutiquement acceptable de ces composés.

  本发明描述了一类用于治疗炎症及炎症状况的取代螺环化合物。特别感兴趣的化合物由通式(III)表示，其中n选自0、1和2；R6选自氢和卤素；R7选自氢和卤素；R8选自氢、卤素、低级烷基、低级烷氧基、低级卤代烷基、低级卤代烷氧基和羟基；R9选自氢、卤素和低级烷基，或者R8和R9共同形成甲氧基亚甲基；R11选自低级烷基和氨基，或这些化合物的药学上可接受的盐。
• SUBSTITUTED SPIRO COMPOUNDS FOR THE TREATMENT OF INFLAMMATION
  申请人：G.D. SEARLE & CO.

  公开号：EP0743938A1

  公开（公告）日：1996-11-27
• US5393790A
  申请人：——

  公开号：US5393790A

  公开（公告）日：1995-02-28
• 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.