4-[6-(4-trifluoromethylphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4-[6-(4-trifluoromethylphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide
• 英文别名: 4-[6-[4-(Trifluoromethyl)phenyl]spiro[2.4]hept-5-en-5-yl]benzenesulfonamide；4-[5-[4-(trifluoromethyl)phenyl]spiro[2.4]hept-5-en-6-yl]benzenesulfonamide
• 化学式: C₂₀H₁₈F₃NO₂S
• 分子量: 393.43
• InChiKey: RWNBBYLXHVHOBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对甲硫基苯甲腈 在 吡啶 、 盐酸 、 titanium(III) chloride 、 三丁基硼 、 溴 、 sodium acetate 、 丙基氯化镁 、 二异丁基氢化铝 、 potassium carbonate 、 间氯过氧苯甲酸 、 potassium iodide 、 sodium iodide 、 hydroxylamine-O-sulfonic acid 、 锌 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醚 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.75h， 生成 4-[6-(4-trifluoromethylphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide
  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

• [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.