1-<2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl>-4-(methylsulfonyl)benzene | 159429-83-1

• 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: 1-<2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl>-4-(methylsulfonyl)benzene
• 英文别名: 1-[2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl]-4-(methylsulfonyl)benzene；Dimethyl 3-(4-fluorophenyl)-4-(4-(methylsulfonyl)phenyl)cyclopent-3-ene-1,1-dicarboxylate；dimethyl 3-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)cyclopent-3-ene-1,1-dicarboxylate
• CAS: 159429-83-1
• 化学式: C₂₂H₂₁FO₆S
• 分子量: 432.47
• InChiKey: DMNYXPUOQSXAER-UHFFFAOYSA-N

物化性质

• 沸点：
  542.2±50.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  95.1
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  1-<2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl>-4-(methylsulfonyl)benzene 在 吡啶 、 三丁基硼 、 sodium acetate 、 丙基氯化镁 、 二异丁基氢化铝 、 sodium iodide 、 hydroxylamine-O-sulfonic acid 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 4-[6-(4-fluorophenyl)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
• 作为产物：
  描述：

  4-甲硫基苯乙酮 在 盐酸 、 氯化亚砜 、 4 A molecular sieve 、 溴 、 lithium hydride 、 二异丁基氢化铝 、 对甲苯磺酸 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 65.83h， 生成 1-<2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl>-4-(methylsulfonyl)benzene
  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 cyclopentenes for the treatment of inflammation
  申请人：G.D. Searle & Co.

  公开号：US05663180A1

  公开（公告）日：1997-09-02

  A class of 1,2-diarylcyclopentenyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: ##STR1## wherein each of R.sup.1 and R.sup.2 is independently selected from alkyl, hydrido, hydroxyalkyl, halo, haloalkyl, alkoxycarbonyl and carboxyl; wherein R.sup.5 is selected from alkylsulfonyl, haloalkylsulfonyl and sulfamyl; and wherein B is phenyl or pyridyl, wherein B is optionally substituted at a substitutable position with alkyl, halo, alkylthio, cyano, haloalkyl, alkoxy, hydroxyalkyl and alkoxyalkyl; or a pharmaceutically-acceptable salt thereof.

  描述了一类1,2-二芳基环戊烯基化合物，用于治疗炎症和与炎症相关的疾病。特别感兴趣的化合物由以下式III定义：其中R.sup.1和R.sup.2中的每一个独立地选自烷基，氢代基，羟基烷基，卤素，卤代烷基，烷氧羰基和羧基；其中R.sup.5选自烷基磺酰基，卤代烷基磺酰基和磺胺基；B选自苯基或吡啶基，其中B在可替换位置可选择性地用烷基，卤素，烷基硫，氰基，卤代烷基，烷氧基，羟基烷基和烷氧基烷基取代；或其药学上可接受的盐。
• Method of preparing sulfmonamides from sulfones
  申请人：G. D. Searle & Co.

  公开号：US05684195A1

  公开（公告）日：1997-11-04

  A one-pot synthesis of sulfonamides from sulfones has been developed. Conversion of sulfones to the corresponding sulfinic acid salts is followed by oxidative-amination to give the sulfonamides.

  已开发出一种从磺酮合成磺胺类化合物的一锅法。将磺酮转化为相应的亚砜酸盐，然后进行氧化胺化反应以得到磺胺类化合物。
• 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，用于治疗炎症和与炎症相关的疾病。特别感兴趣的化合物由公式III定义：其中n是从0、1和2中选择的数字；其中R.sup.3是甲磺酰基或磺酰胺基；其中R.sup.8从氢、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、氟氯二氟甲基、二氟乙基、二氟丙基、二氯乙基、二氯丙基、三氟甲氧基、羟甲基、甲氧甲基和乙氧甲基中选择；或其药学上可接受的盐。
• Pyridyl substituted spirodienes for the treatment of inflammation
  申请人：G. D. Searle & Co.

  公开号：US05670510A1

  公开（公告）日：1997-09-23

  A class of substituted spirodienes is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: ##STR1## wherein A is selected from ##STR2## wherein each of R.sup.1 through R.sup.10 is independently selected from hydrido, halo, alkyl, alkoxy, alkylthio, cyano, haloalkyl, haloalkoxy, hydroxyalkyl; alkoxyalkyl, hydroxyl, mercapto, alkylsulfonyl, haloalkylsulfonyl, and sulfamyl; and wherein n is a number selected from 0, 1, 2 and 3; or a pharmaceutically-acceptable salt thereof.

  描述了一类取代的螺二烯类化合物，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I定义：其中A选自其中每个R1至R10都是独立选择的氢基，卤素，烷基，烷氧基，烷硫基，氰基，卤代烷基，卤代烷氧基，羟基烷基；烷氧基烷基，羟基，巯基，烷基磺酰基，卤代烷基磺酰基和磺酰氨基；其中n是选择的数字0,1,2和3；或其药学上可接受的盐。
• Substituted spirodienes for the treatment of inflammation
  申请人：G.D. Searle & Co.

  公开号：US05672627A1

  公开（公告）日：1997-09-30

  A class of substituted spirodienes is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: ##STR1## 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二烯，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R.sup.3为甲磺酰基或磺酰胺基; R.sup.8从氢、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、甲氧甲基和乙氧甲基; 或其药学上可接受的盐。