methyl 3-{[(7S)-7-{(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-5-(propylamino)benzoate | 1048330-21-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 3-{[(7S)-7-{(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-5-(propylamino)benzoate
• CAS: 1048330-21-7
• 化学式: C₃₄H₄₁ClN₂O₆
• 分子量: 609.162
• InChiKey: JJAKLUCOSLKEOP-IZEXYCQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.57
• 重原子数：
  43.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  97.33
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 3-{[(7S)-7-{(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-5-(propylamino)benzoate 在 盐酸 、 甲醇 、 sodium hydroxide 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-{[(7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-5-(propylamino)benzoic acid dihydrochloride
  参考文献：
  名称：

  Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety

  摘要：

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.

  DOI：

  10.1021/jm800222k
• 作为产物：
  描述：

  7-甲氧基-2-萘满酮 在 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 氢气 、 copper diacetate 、 三溴化硼 、 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 4.0~80.0 ℃ 、3.04 MPa 条件下， 反应 41.0h， 生成 methyl 3-{[(7S)-7-{(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}-5-(propylamino)benzoate
  参考文献：
  名称：

  Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety

  摘要：

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.

  DOI：

  10.1021/jm800222k