5-[2-(9-{4-[1-(2-fluoro-6-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-yloxy]piperidin-4-yl}nonylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one | 1333165-88-0

• 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: 5-[2-(9-{4-[1-(2-fluoro-6-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-yloxy]piperidin-4-yl}nonylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one
• 英文别名: 5-[(1R)-2-[9-[4-[[1-(2-fluoro-6-hydroxyphenyl)-4,5,6,7-tetrahydroindazol-3-yl]oxy]piperidin-1-yl]nonylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one
• CAS: 1333165-88-0
• 化学式: C₃₈H₅₀FN₅O₅
• 分子量: 675.844
• InChiKey: MWNIKTJZFRMVQT-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  132
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,6-二氟苯肼 在 盐酸 、 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 三氧化硫吡啶 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 三苯基膦 、 三氯化磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 、 乙腈 为溶剂， 反应 140.0h， 生成 5-[2-(9-{4-[1-(2-fluoro-6-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-yloxy]piperidin-4-yl}nonylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one
  参考文献：
  名称：

  Efficient Conversion of a Nonselective Norepinephrin Reuptake Inhibitor into a Dual Muscarinic Antagonist−β₂-Agonist for the Treatment of Chronic Obstructive Pulmonary Disease

  摘要：

  Following interrogation of a wide-ligand profile database, a nonselective norepinephrin reuptake inhibitor was converted into a novel muscarinic antagonist using two medicinal chemistry transformations (M3/NRI selectivity of > 1000). Conjugation to a beta(2) agonist motif furnished a molecule with balanced dual pharmacology, as demonstrated in a guinea pig trachea tissue model of bronchoconstriction. This approach provides new starting points for the treatment of chronic obstructive pulmonary disease and illustrates the potential for building selectivity into GPCR modulators that possess intrinsic promiscuity or reverse selectivity.

  DOI：

  10.1021/jm2007535

文献信息

• Efficient Conversion of a Nonselective Norepinephrin Reuptake Inhibitor into a Dual Muscarinic Antagonist−β₂-Agonist for the Treatment of Chronic Obstructive Pulmonary Disease
  作者：Rachel Osborne、Nick Clarke、Paul Glossop、Amy Kenyon、Hao Liu、Sheena Patel、Susan Summerhill、Lyn H. Jones

  DOI：10.1021/jm2007535

  日期：2011.10.13

  Following interrogation of a wide-ligand profile database, a nonselective norepinephrin reuptake inhibitor was converted into a novel muscarinic antagonist using two medicinal chemistry transformations (M3/NRI selectivity of > 1000). Conjugation to a beta(2) agonist motif furnished a molecule with balanced dual pharmacology, as demonstrated in a guinea pig trachea tissue model of bronchoconstriction. This approach provides new starting points for the treatment of chronic obstructive pulmonary disease and illustrates the potential for building selectivity into GPCR modulators that possess intrinsic promiscuity or reverse selectivity.