2-(5-bromo-2-methoxyphenoxy)-5-phenyl-1-pentene | 158429-50-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(5-bromo-2-methoxyphenoxy)-5-phenyl-1-pentene
• 英文别名: 4-Bromo-1-methoxy-2-(5-phenylpent-1-en-2-yloxy)benzene
• CAS: 158429-50-6
• 化学式: C₁₈H₁₉BrO₂
• 分子量: 347.252
• InChiKey: DRHMVUKILNBIKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(5-bromo-2-methoxyphenoxy)-5-phenyl-1-pentene 在 sodium hydroxide 、 四(三苯基膦)钯 、 正丁基锂 、 碘 、 铜 、 zinc(II) chloride 、 锌 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 18.5h， 生成 4-[4-Methoxy-3-[1-(3-phenylpropyl)cyclopropyl]oxyphenyl]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
• 作为产物：
  描述：

  5-溴-2-甲氧基苯酚 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 2-(5-bromo-2-methoxyphenoxy)-5-phenyl-1-pentene
  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

文献信息

• CATECHOL DIETHERS AS SELECTIVE PDE IV? INHIBITORS
  申请人：PFIZER INC.

  公开号：EP0672031A1

  公开（公告）日：1995-09-20
• US5814651A
  申请人：——

  公开号：US5814651A

  公开（公告）日：1998-09-29
• [EN] CATECHOL DIETHERS AS SELECTIVE PDEIV INHIBITORS<br/>[FR] DIETHERS DE PYROCATECHINE UTILISES COMME INHIBITEURS SELECTIFS DE LA PDEIV
  申请人：——

  公开号：WO1994012461A1

  公开（公告）日：1994-06-09

  [EN] This invention relates to 4-substituted catechol diether compounds which are selective inhibitors of phosphodiesterase (PDE) type IV. The compounds of the present invention are useful in inhibiting PDEIV and in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive airways disease, psoriasis, allergic rhinitis, dermatitis and other inflammatory diseases. This invention also relates to pharmaceutical compositions comprising the compounds hereof.
  [FR] L'invention se rapporte à des composés de diéther de pyrocatéchine substitués à la position 4 qui sont des inhibiteurs sélectifs de la phosphodiestérase (PDE) du type IV. Les composés de la présente invention sont utilisés dans l'inhibition de la PDEIV, et dans le traitement du SIDA, de l'asthme, de l'arthrite, de la bronchite, des maladies chroniques obstructives des voies respiratoires, du psoriasis, des rhinites allergiques, des dermatoses et autres maladies inflammatoires. Cette invention se rapporte également à des compositions pharmaceutiques comprenant ces composés.
• Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [³H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret
  作者：Allen J. Duplantier、Michael S. Biggers、Robert J. Chambers、John B. Cheng、Kelvin Cooper、David B. Damon、James F. Eggler、Kenneth G. Kraus、Anthony Marfat、Hiroko Masamune、Joann S. Pillar、John T. Shirley、John P. Umland、John W. Watson

  DOI：10.1021/jm9505066

  日期：1996.1.1

  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).