9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide | 227609-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide
• 英文别名: 9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide；9-(3-bromo-4-fluorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one
• CAS: 227609-25-8
• 化学式: C₁₇H₁₅BrFNO₃S
• 分子量: 412.279
• InChiKey: LHVKVMMIMWOYFR-UHFFFAOYSA-N

物化性质

• 沸点：
  617.4±55.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.0h， 生成 9-[4-fluoro-3-(2-thienyl)phenyl]-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-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
• 作为产物：
  描述：

  1,1-二氧代-四氢-1lambda*6*-噻吩-3-酮 、 3-氨基-2-环己烯-1-酮 、 3-溴-4-氟苯甲醛 以 乙醇 为溶剂， 反应 72.0h， 以10.56 g的产率得到9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-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

• Intranasal administration of modulators of hypothalamic ATP-sensitive potassium channels
  申请人：Herlands Louis

  公开号：US20070026079A1

  公开（公告）日：2007-02-01

  Provided are methods of increasing K ATP channel activity in the hypothalamus of a mammal, methods of reducing glucose production in a mammal, methods of reducing peripheral glucose levels in a mammal, methods of reducing triglyceride levels in a mammal, methods of reducing very low density lipoprotein (VLDL) levels in a mammal, methods of methods of reducing gluconeogenesis in the liver of a mammal, methods of treating metabolic disorders such as diabetes, hyperglycemia, insulin resistance, glucose intolerance, metabolic syndrome and/or obesity, and methods of increasing glucose production and peripheral glucose levels in a mammal. Also provided are methods of treating heart failure, ischemia, coronary heart disease, familial lipoprotein lipase deficiency, hypopituitarism, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, atherosclerosis, hypercholesterolemia, hypertension, polycystic ovary syndrome, gonadotropin deficiency and/or amenorrhea.
• Modulation of Hypothalamic Atp-Sensitive Potassium Channels
  申请人：Rossetti Luciano

  公开号：US20090012067A1

  公开（公告）日：2009-01-08

  Provided are methods of increasing K ATP activity in the hypothalamus of a mammal, methods of reducing glucose production and peripheral blood glucose levels in a mammal, methods of inhibiting gluconeogenesis in the liver of a mammal, and methods of increasing glucose production and peripheral blood glucose levels 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.