tert-butyl (S)-2-(((3-(((phenylcarbamoyl)oxy)methyl)isoxazol-5-yl)oxy)methyl)azetidine-1-carboxylate | 1375143-23-9

• 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: tert-butyl (S)-2-(((3-(((phenylcarbamoyl)oxy)methyl)isoxazol-5-yl)oxy)methyl)azetidine-1-carboxylate
• CAS: 1375143-23-9
• 化学式: C₂₀H₂₅N₃O₆
• 分子量: 403.435
• InChiKey: VRAMWMYATCXUSR-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  103.13
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-(((3-(((phenylcarbamoyl)oxy)methyl)isoxazol-5-yl)oxy)methyl)azetidine-1-carboxylate 、 三氟乙酸 以 二氯甲烷 为溶剂， 以40%的产率得到5-[(2(S)-azetidinyl)methoxy]-3-[(N-phenylcarbamoyloxy)methyl]isoxazole trifluoro acetate
  参考文献：
  名称：

  Identification of Novel α4β2-Nicotinic Acetylcholine Receptor (nAChR) Agonists Based on an Isoxazole Ether Scaffold that Demonstrate Antidepressant-like Activity

  摘要：

  There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.

  DOI：

  10.1021/jm201301h
• 作为产物：
  描述：

  (S)-1-BOC-2-氮杂环丁烷甲醇 在 4-二甲氨基吡啶 、 锂硼氢 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.0h， 生成 tert-butyl (S)-2-(((3-(((phenylcarbamoyl)oxy)methyl)isoxazol-5-yl)oxy)methyl)azetidine-1-carboxylate
  参考文献：
  名称：

  Identification of Novel α4β2-Nicotinic Acetylcholine Receptor (nAChR) Agonists Based on an Isoxazole Ether Scaffold that Demonstrate Antidepressant-like Activity

  摘要：

  There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.

  DOI：

  10.1021/jm201301h