8-(3-bromo-4-fluorophenyl)-2,3,4,5,6,8-hexahydro-7H-cyclopenta[b]thieno[2,3-e]pyridine-7-one 1,1-dioxide | 227609-38-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-(3-bromo-4-fluorophenyl)-2,3,4,5,6,8-hexahydro-7H-cyclopenta[b]thieno[2,3-e]pyridine-7-one 1,1-dioxide
• 英文别名: 8-(3-bromo-4-fluorophenyl)-3,5,6,8-tetrahydro-2H-cyclopenta[b]thieno[2,3-e]pyridin-7(4H)-one,1,1-dioxide；8-(3-bromo-4-fluorophenyl)-2,3,4,5,6,8-hexahydro-7H-cyclopenta[b]thieno[2,3-e]pyridin-7-one,1,1-dioxide；8-(3-Bromo-4-fluorophenyl)-6,6-dioxo-6lambda6-thia-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-dien-10-one；8-(3-bromo-4-fluorophenyl)-6,6-dioxo-6λ6-thia-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-dien-10-one
• CAS: 227609-38-3
• 化学式: C₁₆H₁₃BrFNO₃S
• 分子量: 398.253
• InChiKey: KYPRKYQAMNMLQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(3-bromo-4-fluorophenyl)-2,3,4,5,6,8-hexahydro-7H-cyclopenta[b]thieno[2,3-e]pyridine-7-one 1,1-dioxide 以264 mg的产率得到(8R)-8-(3-bromo-4-fluorophenyl)-6,6-dioxo-6lambda6-thia-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-dien-10-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
• 作为产物：
  描述：

  1,1-二氧代-四氢-1lambda*6*-噻吩-3-酮 、 3-氨基环戊-2-烯-1-酮 、 3-溴-4-氟苯甲醛 以 乙醇 为溶剂， 反应 72.0h， 以241 mg的产率得到8-(3-bromo-4-fluorophenyl)-2,3,4,5,6,8-hexahydro-7H-cyclopenta[b]thieno[2,3-e]pyridine-7-one 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

文献信息

• 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.