5-cyclohexyl-3-hydroxyisoxazole | 27772-75-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-cyclohexyl-3-hydroxyisoxazole
• 英文别名: 5-cyclohexyl-3-isoxazolol；5-cyclohexyl-isoxazol-3-one；5-cyclohexyl-1,2-oxazol-3-one
• CAS: 27772-75-4
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: OCQUSXAFBGDPBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-cyclohexyl-3-hydroxyisoxazole 在 氢溴酸 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 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
• 作为产物：
  描述：

  5-(cyclohexylhydroxymethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 盐酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 9.0h， 生成 5-cyclohexyl-3-hydroxyisoxazole
  参考文献：
  名称：

  5-取代的3-异恶唑醇的新颖途径。通过酰基麦德鲁姆酸合成的N，O-DiBocβ-酮异羟肟酸的环化反应。

  摘要：

  3-异恶唑醇最通常由β-酮酯和羟胺合成。该环化通常产生主要副产物，相应的5-异恶唑酮。我们已经发现，可以合成N，O-diBoc保护的β-酮异羟肟酸并将其环化成5-取代的3-异恶唑醇，而不会形成任何副产物。我们提出了一种新颖且通用的三步程序，其中将羧酸衍生物转化为酰基麦德鲁姆酸，当与N，O-双（叔丁氧基羰基）羟胺进行氨解后，会生成N，O-diBoc保护的β-酮异羟肟酸。然后，将这些异羟肟酸类似物用盐酸处理后，环化成相应的5-取代的3-异恶唑醇。

  DOI：

  10.1021/jo991409d

文献信息

• Jacquier,R. et al., Bulletin de la Societe Chimique de France, 1970, p. 2685 - 2690
  作者：Jacquier,R. et al.

  DOI：——

  日期：——
• Jacquier,R. et al., Bulletin de la Societe Chimique de France, 1970, p. 1978 - 1985
  作者：Jacquier,R. et al.

  DOI：——

  日期：——
• Aryl and cycloalkyl analogues of AMPA: synthetic, pharmacological and stereochemical aspects
  作者：Niels Skjærbæk、Lotte Brehm、Tommy N. Johansen、Lene M. Hansen、Birgitte Nielsen、Bjarke Ebert、Karina K. Søby、Tine B. Stensbøl、Erik Falch、Povl Krogsgaard-Larsen

  DOI：10.1016/s0968-0896(97)10017-7

  日期：1998.1

  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.
• A Novel Route to 5-Substituted 3-Isoxazolols. Cyclization of <i>N,O-</i>DiBoc β-Keto Hydroxamic Acids Synthesized via Acyl Meldrum's Acids
  作者：Ulrik S. Sørensen、Erik Falch、Povl Krogsgaard-Larsen

  DOI：10.1021/jo991409d

  日期：2000.2.1

  We have found that N, O-diBoc-protected beta-keto hydroxamic acids can be synthesized and cyclized to 5-substituted 3-isoxazolols without formation of any byproduct. We present a novel and versatile three-step procedure in which carboxylic acid derivatives are converted into acyl Meldrum's acids which, upon aminolysis with N, O-bis(tert-butoxycarbonyl)hydroxylamine, lead to the N, O-diBoc-protected

  3-异恶唑醇最通常由β-酮酯和羟胺合成。该环化通常产生主要副产物，相应的5-异恶唑酮。我们已经发现，可以合成N，O-diBoc保护的β-酮异羟肟酸并将其环化成5-取代的3-异恶唑醇，而不会形成任何副产物。我们提出了一种新颖且通用的三步程序，其中将羧酸衍生物转化为酰基麦德鲁姆酸，当与N，O-双（叔丁氧基羰基）羟胺进行氨解后，会生成N，O-diBoc保护的β-酮异羟肟酸。然后，将这些异羟肟酸类似物用盐酸处理后，环化成相应的5-取代的3-异恶唑醇。