[4-((7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butylcoxycarbonylamino}-5,6,7,8-tetrahydro-2-naphthalenyl)phenoxy]-tert-butyldimethylsilane | 603122-33-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: [4-((7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butylcoxycarbonylamino}-5,6,7,8-tetrahydro-2-naphthalenyl)phenoxy]-tert-butyldimethylsilane
• 英文别名: tert-butyl N-[(2S)-7-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1,2,3,4-tetrahydronaphthalen-2-yl]-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]carbamate
• CAS: 603122-33-4
• 化学式: C₃₅H₄₆ClNO₄Si
• 分子量: 608.293
• InChiKey: YATXTXABKSEQLN-CDZUIXILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.22
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-((7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butylcoxycarbonylamino}-5,6,7,8-tetrahydro-2-naphthalenyl)phenoxy]-tert-butyldimethylsilane 在 盐酸 、 甲醇 、 sodium hydroxide 、 四丁基氟化铵 、 水 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 [4-((7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydro-2-naphthalenyl)phenoxy]acetic acid hydrochloride
  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：

  (S)-2-氨基-7-羟基四氢化萘 在 2,6-二甲基吡啶 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 [4-((7S)-7-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-tert-butylcoxycarbonylamino}-5,6,7,8-tetrahydro-2-naphthalenyl)phenoxy]-tert-butyldimethylsilane
  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