2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-(3,5-dichloro-2-hydroxybenzyl)acetamide | 1246459-99-3

• 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: 2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-(3,5-dichloro-2-hydroxybenzyl)acetamide
• 英文别名: 2-[3-[2-[[(2R)-2-[tert-butyl(dimethyl)silyl]oxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]-N-[(3,5-dichloro-2-hydroxyphenyl)methyl]acetamide
• CAS: 1246459-99-3
• 化学式: C₃₄H₄₇Cl₂N₃O₆SSi
• 分子量: 724.821
• InChiKey: HZSBJSBMIOEBBI-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.31
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-(3,5-dichloro-2-hydroxybenzyl)acetamide 在 氟化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 以78%的产率得到N-(3,5-dichloro-2-hydroxybenzyl)-2-[3-(2-{[(2R)-2-hydroxy-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]acetamide
  参考文献：
  名称：

  Inhalation by Design: Novel Ultra-Long-Acting β₂-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup

  摘要：

  A novel series of potent and selective sulfonamide derived beta(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming, its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.

  DOI：

  10.1021/jm1005989
• 作为产物：
  描述：

  (3-{2-[(2R)-2-(tert-butyldimethylsilyloxy)-2-(4-hydroxy-3-methanesulfonylaminophenyl)ethylamino]-2-methylpropyl}phenyl)acetic acid 、 3,5-二氯-2-羟基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以50%的产率得到2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-(3,5-dichloro-2-hydroxybenzyl)acetamide
  参考文献：
  名称：

  Inhalation by Design: Novel Ultra-Long-Acting β₂-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup

  摘要：

  A novel series of potent and selective sulfonamide derived beta(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming, its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.

  DOI：

  10.1021/jm1005989

文献信息

• Inhalation by Design: Novel Ultra-Long-Acting β₂-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup
  作者：Paul A. Glossop、Charlotte A. L. Lane、David A. Price、Mark E. Bunnage、Russell A. Lewthwaite、Kim James、Alan D. Brown、Michael Yeadon、Christelle Perros-Huguet、Michael A. Trevethick、Nicholas P. Clarke、Robert Webster、Rhys M. Jones、Jane L. Burrows、Neil Feeder、Stefan C. J. Taylor、Fiona J. Spence

  DOI：10.1021/jm1005989

  日期：2010.9.23

  A novel series of potent and selective sulfonamide derived beta(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming, its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.