2-{3-[(2R)-2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}propyl]phenyl}-N-(2-methoxybenzyl)acetamide | 861449-72-1

• 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-[(2R)-2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}propyl]phenyl}-N-(2-methoxybenzyl)acetamide
• 英文别名: 2-[3-[(2R)-2-[[(2R)-2-[tert-butyl(dimethyl)silyl]oxy-2-[3-(methanesulfonamido)-4-phenylmethoxyphenyl]ethyl]amino]propyl]phenyl]-N-[(2-methoxyphenyl)methyl]acetamide
• CAS: 861449-72-1
• 化学式: C₄₁H₅₅N₃O₆SSi
• 分子量: 746.056
• InChiKey: YAKXEMIYQALQGU-MFIBOOTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.79
• 重原子数：
  52
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-{3-[(2R)-2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}propyl]phenyl}-N-(2-methoxybenzyl)acetamide 在 20 % Pd(OH)2/C 、 甲酸铵 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成
  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：

  邻甲氧基苄胺 、 (3-{(2R)-2-[((2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl-(dimethyl)silyl]oxy}ethyl)amino]propyl}phenyl)acetic acid 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54%的产率得到2-{3-[(2R)-2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}propyl]phenyl}-N-(2-methoxybenzyl)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