2,3-dibromo-3-cyclohexylpropionic acid methyl ester | 81852-61-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2,3-dibromo-3-cyclohexylpropionic acid methyl ester
• 英文别名: Methyl 2,3-dibromo-3-cyclohexylpropanoate
• CAS: 81852-61-1
• 化学式: C₁₀H₁₆Br₂O₂
• 分子量: 328.044
• InChiKey: YYXKXNBFWNSORN-UHFFFAOYSA-N

物化性质

• 沸点：
  313.6±22.0 °C(Predicted)
• 密度：
  1.597±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-cyclohexylacrylic acid methyl ester 在 溴 作用下， 以 氯仿 为溶剂， 以95%的产率得到2,3-dibromo-3-cyclohexylpropionic acid methyl ester
  参考文献：
  名称：

  Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity

  摘要：

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.

  DOI：

  10.1021/jm00063a002

文献信息

• A SIMPLE SYNTHESIS OF 2-AZIDO-2-ALKENOATES
  作者：Masa-aki Kakimoto、Mariko Kai、Kiyosi Kondo

  DOI：10.1246/cl.1982.525

  日期：1982.4.5

  The title compounds are derived from 2,3-dibromoalkanoates by treatment with 3 equivalents of sodium azide.

  用 3 个等量的叠氮化钠处理 2,3-二溴烷酸酯，可得到标题化合物。
• KAKIMOTO, MASA-AKI;KAI, MARIKO;KONDO, KIYOSI, CHEM. LETT., 1982, N 4, 525-526
  作者：KAKIMOTO, MASA-AKI、KAI, MARIKO、KONDO, KIYOSI

  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.
• Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity
  作者：Wilma Quaglia、Maria Pigini、Seyed K. Tayebati、Alessandro Piergentili、Mario Giannella、Gabriella Marucci、Carlo Melchiorre

  DOI：10.1021/jm00063a002

  日期：1993.5

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.