C-[5-(3-Chloro-1-methyl-propyl)-3-methoxy-isoxazol-4-yl]-methylamine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: C-[5-(3-Chloro-1-methyl-propyl)-3-methoxy-isoxazol-4-yl]-methylamine
• 英文别名: [5-(4-Chlorobutan-2-yl)-3-methoxy-1,2-oxazol-4-yl]methanamine
• 化学式: C₉H₁₅ClN₂O₂
• 分子量: 218.683
• InChiKey: AVCVRGGWBYRUNQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  61.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  C-[5-(3-Chloro-1-methyl-propyl)-3-methoxy-isoxazol-4-yl]-methylamine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 (RS)-3-methoxy-8-methyl-5,6,7,8-tetrahydro-4H-isoxazolo<4,5-c>azepine
  参考文献：
  名称：

  Muscarinic agonists. Syntheses and structure—activity relationships of bicyclic isoxazole ester bioisosteres of norarecoline

  摘要：

  (RS)-3-Methoxy-8-methyl-5,6,7,8-tetrahydra-4H-isoxazolo[4,5-c]azepine (O,8-di-Me-THAO, 2c) and (RS)-8-methyl-3- propargyloxy-5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepine (8-Me-O-propargyl-THAO, 2d) have been synthesized and evaluated as muscarinic receptor ligands in receptor binding assays and in in vitro functional assays. The corresponding compounds without methyl groups at C-8, ie O-Me THAO (2a) and O-propargyl-THAO (2b), have previously been shown to exhibit muscarinic agonistic profiles with very little discrimination between M(1)- and M(2)-receptor sites. Based on functional assays, 2c and 2d were found to be less efficacious than 2a and 2b, respectively, and 2d proved to be an M(1)-selective partial agonist. The-affinity and M(1) efficacy of 2c and 2d were comparable to those of the corresponding six-membered ring analogues, (RS)-3-methoxy-7-methyl-4,5,6,7-tetrahydro-isoxazolo[4,5-c]pyridine (O,7-di-Me-THPO, 1c) and (RS)-7-methyl-3-propargyloxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine (7-Me-O-propargyl-THPO, 1d). However, neither compound 1c nor compound 1d-displayed M(1) selectivity. In summary, within this class of bicyclic muscaninic agonists, replacement of 3-methoxy by 3-propargyloxy groups generally increases muscarinic affinity without effecting the efficacy at M(1) receptors significantly. Introduction of a methyl group into the saturated ring, at the position alpha to the C-5 of the isoxazole ring (alpha-position) lead to compounds exerting lower efficacy and, in the case of compound 2d, an increased selectivity with respect to M(1) agonism.

  DOI：

  10.1016/0223-5234(96)88234-1
• 作为产物：
  描述：

  (RS)-4-aminomethyl-3-methoxy-5-(4-hydroxy-2-butyl)isoxazole 在 盐酸 、 氯化亚砜 作用下， 生成 C-[5-(3-Chloro-1-methyl-propyl)-3-methoxy-isoxazol-4-yl]-methylamine
  参考文献：
  名称：

  Muscarinic agonists. Syntheses and structure—activity relationships of bicyclic isoxazole ester bioisosteres of norarecoline

  摘要：

  (RS)-3-Methoxy-8-methyl-5,6,7,8-tetrahydra-4H-isoxazolo[4,5-c]azepine (O,8-di-Me-THAO, 2c) and (RS)-8-methyl-3- propargyloxy-5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepine (8-Me-O-propargyl-THAO, 2d) have been synthesized and evaluated as muscarinic receptor ligands in receptor binding assays and in in vitro functional assays. The corresponding compounds without methyl groups at C-8, ie O-Me THAO (2a) and O-propargyl-THAO (2b), have previously been shown to exhibit muscarinic agonistic profiles with very little discrimination between M(1)- and M(2)-receptor sites. Based on functional assays, 2c and 2d were found to be less efficacious than 2a and 2b, respectively, and 2d proved to be an M(1)-selective partial agonist. The-affinity and M(1) efficacy of 2c and 2d were comparable to those of the corresponding six-membered ring analogues, (RS)-3-methoxy-7-methyl-4,5,6,7-tetrahydro-isoxazolo[4,5-c]pyridine (O,7-di-Me-THPO, 1c) and (RS)-7-methyl-3-propargyloxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine (7-Me-O-propargyl-THPO, 1d). However, neither compound 1c nor compound 1d-displayed M(1) selectivity. In summary, within this class of bicyclic muscaninic agonists, replacement of 3-methoxy by 3-propargyloxy groups generally increases muscarinic affinity without effecting the efficacy at M(1) receptors significantly. Introduction of a methyl group into the saturated ring, at the position alpha to the C-5 of the isoxazole ring (alpha-position) lead to compounds exerting lower efficacy and, in the case of compound 2d, an increased selectivity with respect to M(1) agonism.

  DOI：

  10.1016/0223-5234(96)88234-1