4-[(R)-2-{[(S)-2-(3-bromoisoxazol-5-yl)-2-hydroxyethyl]tert-butoxycarbonylamino}propyl]phenol | 933055-67-5

• 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: 4-[(R)-2-{[(S)-2-(3-bromoisoxazol-5-yl)-2-hydroxyethyl]tert-butoxycarbonylamino}propyl]phenol
• CAS: 933055-67-5
• 化学式: C₁₉H₂₅BrN₂O₅
• 分子量: 441.322
• InChiKey: SHYOAQHZGZWNGW-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  96.03
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-[(R)-2-{[(S)-2-(3-bromoisoxazol-5-yl)-2-hydroxyethyl]tert-butoxycarbonylamino}propyl]phenol 在 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 60.0h， 生成 (S)-1-(3-bromoisoxazol-5-yl)-2-{[(R)-2-(4-butoxyphenyl)-1-methylethyl]amino}ethanol trifluoroacetate
  参考文献：
  名称：

  Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes

  摘要：

  Isoxazole derivative (+/-)-4 and the three pairs of stereoisomeric 3-bromo-isoxazolyl amino alcohols (S,R)-(-)-7a/(R,R)(+)-7b, (S, R)-(-)-8a/(R, R)-(+)-8b, and (S, R)-(-)-9a/(R, R)-(+)-9b were synthesized and assayed for their affinity and efficacy at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptors (beta-ARs) in membranes from Chinese hamster ovary (CHO) cells stably transfected with the respective receptor subtype. Whereas derivative ()-4 did not bind at all three P-ARs, stereoisomers (S, R)-7a-(S, R)-9a behaved as high-affinity ligands at beta(1)- and, particularly, at beta(2)-ARs (K-i 2.82-66.7 nM). The Ki values of isomers (R,R)-7b-(R,R)-9b at beta(1)- and beta(2)-subtypes were about 30-100 times higher than those of their (S, R)-7a-9a counterparts, indicating a sizable stereochemical effect. The affinity at beta(3)-ARs was negligible for all the investigated compounds. When submitted to a functional assay, the three stereoisomeric pairs showed a comparable pattern of efficacy at all three beta-AR subtypes. The highest value of efficacy (75-90%) was observed at beta(2)-ARs, whereas all compounds behaved as partial agonists (30-60%) at the beta(3)-subtype. The lowest degree of efficacy (15-35%) was found at beta(1)-ARs. The affinity/efficacy profile of the derivatives under study has been compared with that of the two model compounds, Broxaterol [(+/-)-1] and BRL 37344 [(+/-)-6]. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.056
• 作为产物：
  描述：

  (S)-1-(3-bromoisoxazol-5-yl)-2-{[(R)-2-(4-methoxyphenyl)-1-methylethyl]-tert-butoxycarbonylamino}ethanol 在 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.0h， 生成 4-[(R)-2-{[(S)-2-(3-bromoisoxazol-5-yl)-2-hydroxyethyl]tert-butoxycarbonylamino}propyl]phenol
  参考文献：
  名称：

  Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes

  摘要：

  Isoxazole derivative (+/-)-4 and the three pairs of stereoisomeric 3-bromo-isoxazolyl amino alcohols (S,R)-(-)-7a/(R,R)(+)-7b, (S, R)-(-)-8a/(R, R)-(+)-8b, and (S, R)-(-)-9a/(R, R)-(+)-9b were synthesized and assayed for their affinity and efficacy at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptors (beta-ARs) in membranes from Chinese hamster ovary (CHO) cells stably transfected with the respective receptor subtype. Whereas derivative ()-4 did not bind at all three P-ARs, stereoisomers (S, R)-7a-(S, R)-9a behaved as high-affinity ligands at beta(1)- and, particularly, at beta(2)-ARs (K-i 2.82-66.7 nM). The Ki values of isomers (R,R)-7b-(R,R)-9b at beta(1)- and beta(2)-subtypes were about 30-100 times higher than those of their (S, R)-7a-9a counterparts, indicating a sizable stereochemical effect. The affinity at beta(3)-ARs was negligible for all the investigated compounds. When submitted to a functional assay, the three stereoisomeric pairs showed a comparable pattern of efficacy at all three beta-AR subtypes. The highest value of efficacy (75-90%) was observed at beta(2)-ARs, whereas all compounds behaved as partial agonists (30-60%) at the beta(3)-subtype. The lowest degree of efficacy (15-35%) was found at beta(1)-ARs. The affinity/efficacy profile of the derivatives under study has been compared with that of the two model compounds, Broxaterol [(+/-)-1] and BRL 37344 [(+/-)-6]. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.056