4-(bromomethyl)-5-cyclohexyl-2-(methoxymethyl)isoxazolin-3-one | 203718-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(bromomethyl)-5-cyclohexyl-2-(methoxymethyl)isoxazolin-3-one
• CAS: 203718-21-2
• 化学式: C₁₂H₁₈BrNO₃
• 分子量: 304.184
• InChiKey: GBCLXPZTPOSDTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  44.37
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(bromomethyl)-5-cyclohexyl-2-(methoxymethyl)isoxazolin-3-one 在 sodium hydride 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 2-Amino-3-(5-cyclohexyl-3-hydroxy-isoxazol-4-yl)-propionic acid
  参考文献：
  名称：

  Aryl and cycloalkyl analogues of AMPA: synthetic, pharmacological and stereochemical aspects

  摘要：

  We have previously shown that (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA, 2) is a functional partial agonist at the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors, reflecting that (S)-APPA is a full agonist and (R)-APPA a competitive antagonist at AMPA receptors. We have now synthesized and pharmacologically characterized (RS)-2-amino-3-[3-hydroxy-5-(2-fluorophenyl)isoxazol-4-yl]propionic acid (2-F-APPA, 5a), 3-F-APPA (5b), 4-F-APPA (5c), (S)-4-F-APPA (6), (R)-4-F-APPA (7), and the fully and partially, respectively, saturated APPA (2) analogues, (RS)-2-amino-3-(3-hydroxy-5-cyclohexylisoxazol-4-yl)propionic acid (5d) and compound 5e containing a 1-cyclohexenyl ring. The absolute stereochemistry of 6 and 7 was established on the basis of comparative circular dichroism studies on 6, 7, and (S)- and (R)-APPA. 4-F-APPA (5c), (S)-4-F-APPA (6), 5d, and 5e were shown to selectively inhibit [H-3]AMPA binding and to activate AMPA receptors. Whereas (S)-4-F-APPA (6) showed full AMPA receptor agonism, (R)-4-F-APPA (7) was an AMPA receptor antagonist. Co-administration of (S)- and (R)-4-F-APPA to the rat cortical wedge preparation produced functional partial AMPA receptor agonism. Semi empirical calculations showed that the magnitude of the torsional angle of the bond connecting the two rings in the series of nonannulated bicyclic AMPA analogues appears to be of importance for the potency and efficacy of these compounds. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10017-7
• 作为产物：
  描述：

  2,3-dibromo-3-cyclohexylpropionic acid methyl ester 在 sodium hydroxide 、 羟基脲 、 氢溴酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 4-(bromomethyl)-5-cyclohexyl-2-(methoxymethyl)isoxazolin-3-one
  参考文献：
  名称：

  Aryl and cycloalkyl analogues of AMPA: synthetic, pharmacological and stereochemical aspects

  摘要：

  We have previously shown that (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA, 2) is a functional partial agonist at the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors, reflecting that (S)-APPA is a full agonist and (R)-APPA a competitive antagonist at AMPA receptors. We have now synthesized and pharmacologically characterized (RS)-2-amino-3-[3-hydroxy-5-(2-fluorophenyl)isoxazol-4-yl]propionic acid (2-F-APPA, 5a), 3-F-APPA (5b), 4-F-APPA (5c), (S)-4-F-APPA (6), (R)-4-F-APPA (7), and the fully and partially, respectively, saturated APPA (2) analogues, (RS)-2-amino-3-(3-hydroxy-5-cyclohexylisoxazol-4-yl)propionic acid (5d) and compound 5e containing a 1-cyclohexenyl ring. The absolute stereochemistry of 6 and 7 was established on the basis of comparative circular dichroism studies on 6, 7, and (S)- and (R)-APPA. 4-F-APPA (5c), (S)-4-F-APPA (6), 5d, and 5e were shown to selectively inhibit [H-3]AMPA binding and to activate AMPA receptors. Whereas (S)-4-F-APPA (6) showed full AMPA receptor agonism, (R)-4-F-APPA (7) was an AMPA receptor antagonist. Co-administration of (S)- and (R)-4-F-APPA to the rat cortical wedge preparation produced functional partial AMPA receptor agonism. Semi empirical calculations showed that the magnitude of the torsional angle of the bond connecting the two rings in the series of nonannulated bicyclic AMPA analogues appears to be of importance for the potency and efficacy of these compounds. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10017-7