(S)-(-)-4-[4-methoxy-3-(5-phenylpent-2-yloxy)phenyl]benzoic acid | 158514-50-2

• 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: (S)-(-)-4-[4-methoxy-3-(5-phenylpent-2-yloxy)phenyl]benzoic acid
• 英文别名: 4-[4-methoxy-3-[(2S)-5-phenylpentan-2-yl]oxyphenyl]benzoic acid
• CAS: 158514-50-2
• 化学式: C₂₅H₂₆O₄
• 分子量: 390.479
• InChiKey: TXOWTJJUOMBYJF-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(-)-4-[4-methoxy-3-(5-phenylpent-2-yloxy)phenyl]benzoic acid 在 氯化亚砜 作用下， 反应 1.5h， 生成 4'-Methoxy-3'-((S)-1-methyl-4-phenyl-butoxy)-biphenyl-4-carbonyl chloride
  参考文献：
  名称：

  Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [³H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret

  摘要：

  In addition to having desirable inhibitory effects on inflammation, anaphylaxis, and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side effects including nausea and vomiting. In general, compounds that inhibit PDE-IV also potently displace [H-3]rolipram from a high-affinity binding site in rat cortex.(1,2) While this binding site has not been identified, it has been proposed to be an allosteric binding site on the PDE-IV enzyme.(3) Preliminary studies have suggested that the emetic potency of PDE-IV inhibitors is correlated with affinity for the brain rolipram binding site rather than potency at inhibiting PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV inhibitors were directed toward developing compounds with decreased [H-3]rolipram binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3-alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were prepared and evaluated for their PDE-IV inhibitory and rolipram binding site properties. Modification of the catechol ether moiety led to phenylbutoxy and phenylpentoxy analogues that provided the desired actitivity profile. Specifically, 4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to exhibit potent PDE-IV inhibitory activity (IC50 0.41 mu M) and possessed 400 times weaker activity than rolipram for the [H-3]rolipram binding site. In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED(50) 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).

  DOI：

  10.1021/jm9505066
• 作为产物：
  描述：

  5-溴-2-甲氧基苯酚 在 sodium hydroxide 、 四(三苯基膦)钯 、 正丁基锂 、 三苯基膦 、 zinc(II) chloride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 19.5h， 生成 (S)-(-)-4-[4-methoxy-3-(5-phenylpent-2-yloxy)phenyl]benzoic acid
  参考文献：
  名称：

  Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [³H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret

  摘要：

  In addition to having desirable inhibitory effects on inflammation, anaphylaxis, and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side effects including nausea and vomiting. In general, compounds that inhibit PDE-IV also potently displace [H-3]rolipram from a high-affinity binding site in rat cortex.(1,2) While this binding site has not been identified, it has been proposed to be an allosteric binding site on the PDE-IV enzyme.(3) Preliminary studies have suggested that the emetic potency of PDE-IV inhibitors is correlated with affinity for the brain rolipram binding site rather than potency at inhibiting PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV inhibitors were directed toward developing compounds with decreased [H-3]rolipram binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3-alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were prepared and evaluated for their PDE-IV inhibitory and rolipram binding site properties. Modification of the catechol ether moiety led to phenylbutoxy and phenylpentoxy analogues that provided the desired actitivity profile. Specifically, 4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to exhibit potent PDE-IV inhibitory activity (IC50 0.41 mu M) and possessed 400 times weaker activity than rolipram for the [H-3]rolipram binding site. In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED(50) 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).

  DOI：

  10.1021/jm9505066