N-benzyl-N-(3-((1R)-2-iodo-1-triethylsilyloxy-ethyl)phenyl)methanesulfonamide | 320728-11-8

• 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: N-benzyl-N-(3-((1R)-2-iodo-1-triethylsilyloxy-ethyl)phenyl)methanesulfonamide
• 英文别名: (R)-N-benzyl-N-[3-[2-iodo-1-[(triethylsilyl)oxy]ethyl]phenyl]methanesulfonamide；N-benzyl-N-[3-[(1R)-2-iodo-1-triethylsilyloxyethyl]phenyl]methanesulfonamide
• CAS: 320728-11-8
• 化学式: C₂₂H₃₂INO₃SSi
• 分子量: 545.557
• InChiKey: VTPFBFTZRQVGED-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.15
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyl-N-(3-((1R)-2-iodo-1-triethylsilyloxy-ethyl)phenyl)methanesulfonamide 在 盐酸 、 4-二甲氨基吡啶 、 偶氮二甲酰胺 、 20% palladium hydroxide-activated charcoal 、 氢气 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 甲基叔丁基醚 、 甲苯 为溶剂， 生成 N-(3-((1R)-1-hydroxy-2-(2-((3-methoxy-1H-indazol-6-yl)oxy)ethylamino)ethyl)phenyl)methanesulfonamide dihydrochloride
  参考文献：
  名称：

  Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β₃-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects

  摘要：

  Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human A-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant beta(3)-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the alpha(1A)-AR (EC50 = 219 nM, selectivity: alpha(1A)/beta(3) = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for beta(3)-AR agonistic activity versus au-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent beta(3)-AR agonistic activity (EC50 = 13 nM) and high selectivity (alpha(1A)/beta(3) = >769-fold). Compound 11 was also inactive toward beta(1) and beta(2)-ARs and showed dose dependent beta(3)-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.

  DOI：

  10.1021/acs.jmedchem.5b00638