4-(3-bromo-4-fluorophenyl)-1,1,1-trifluoro-3-buten-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 4-(3-bromo-4-fluorophenyl)-1,1,1-trifluoro-3-buten-2-one
• 英文别名: (E)-4-(3-bromo-4-fluorophenyl)-1,1,1-trifluorobut-3-en-2-one
• 化学式: C₁₀H₅BrF₄O
• 分子量: 297.047
• InChiKey: VWXSGSULYIRQIT-DUXPYHPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-bromo-4-fluorophenyl)-1,1,1-trifluoro-3-buten-2-one 在 ammonium hydroxide 、 对甲苯磺酸 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 1.0h， 生成 (+)-7-(3-bromo-4-fluorophenyl)-5-(trifluoromethyl)-2,3,4,7-tetrahydrothieno[3,2-b]pyridine,1,1-dioxide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a Novel Series of 2,3,5,6,7,9-Hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-Dioxide K_ATP Channel Openers:  Discovery of (−)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-Dioxide (A-278637), a Potent K_ATP Opener That Selectively Inhibits Spontaneous Bladder Contractions

  摘要：

  Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing K-ATP openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K-ATP activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than I in vivo and supports the concept that bladder-selective K-ATP channel openers may have utility in the treatment of overactive bladder.

  DOI：

  10.1021/jm030356w
• 作为产物：
  描述：

  1,1,1-三氟丙酮 、 3-溴-4-氟苯甲醛 在 哌啶 、 溶剂黄146 作用下， 以 苯 为溶剂， 以226 mg的产率得到4-(3-bromo-4-fluorophenyl)-1,1,1-trifluoro-3-buten-2-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a Novel Series of 2,3,5,6,7,9-Hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-Dioxide K_ATP Channel Openers:  Discovery of (−)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-Dioxide (A-278637), a Potent K_ATP Opener That Selectively Inhibits Spontaneous Bladder Contractions

  摘要：

  Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing K-ATP openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K-ATP activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than I in vivo and supports the concept that bladder-selective K-ATP channel openers may have utility in the treatment of overactive bladder.

  DOI：

  10.1021/jm030356w

文献信息

• POTASSIUM CHANNEL OPENERS
  申请人：Abbott Laboratories

  公开号：EP1194429A1

  公开（公告）日：2002-04-10
• [EN] POTASSIUM CHANNEL OPENERS<br/>[FR] AGENTS D'OUVERTURE DE CANAL POTASSIQUE
  申请人：ABBOTT LAB

  公开号：WO2000078768A1

  公开（公告）日：2000-12-28

  Compounds having formula (I) are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
• Synthesis and Structure−Activity Relationships of a Novel Series of 2,3,5,6,7,9-Hexahydrothieno[3,2-<i>b</i>]quinolin-8(4<i>H</i>)-one 1,1-Dioxide K_ATP Channel Openers:  Discovery of (−)-(9<i>S</i>)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-<i>b</i>]quinolin-8(4<i>H</i>)-one 1,1-Dioxide (A-278637), a Potent K_ATP Opener That Selectively Inhibits Spontaneous Bladder Contractions
  作者：William A. Carroll、Robert J. Altenbach、Hao Bai、Jorge D. Brioni、Michael E. Brune、Steven A. Buckner、Christopher Cassidy、Yiyuan Chen、Michael J. Coghlan、Anthony V. Daza、Irene Drizin、Thomas A. Fey、Michael Fitzgerald、Murali Gopalakrishnan、Robert J. Gregg、Rodger F. Henry、Mark W. Holladay、Linda L. King、Michael E. Kort、Philip R. Kym、Ivan Milicic、Rui Tang、Sean C. Turner、Kristi L. Whiteaker、Lin Yi、Henry Zhang、James P. Sullivan

  DOI：10.1021/jm030356w

  日期：2004.6.1

  Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing K-ATP openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K-ATP activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than I in vivo and supports the concept that bladder-selective K-ATP channel openers may have utility in the treatment of overactive bladder.