苯酚,3-氟-5-[四氢-4-(甲磺酰)-2H-吡喃-4-基]- | 167758-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 苯酚,3-氟-5-[四氢-4-(甲磺酰)-2H-吡喃-4-基]-
• 英文名称: 4-(5-hydroxy-3-fluorophenyl)-4-methylsulfonyl-3,4,5,6-tetrahydro-2H-pyran
• 英文别名: 3-Fluoro-5-(4-methylsulfonyloxan-4-yl)phenol
• CAS: 167758-69-2
• 化学式: C₁₂H₁₅FO₄S
• 分子量: 274.313
• InChiKey: QGVRCGWGHAIFFL-UHFFFAOYSA-N

物化性质

• 沸点：
  508.2±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-氯甲基苯基)-2-甲基-1H-咪唑 、 苯酚,3-氟-5-[四氢-4-(甲磺酰)-2H-吡喃-4-基]- 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-{4-[3-Fluoro-5-(4-methanesulfonyl-tetrahydro-pyran-4-yl)-phenoxymethyl]-phenyl}-2-methyl-1H-imidazole
  参考文献：
  名称：

  4-[5-Fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5,6- tetrahydro-2H-pyran-4-carboxamide, an Orally Active Inhibitor of 5-Lipoxygenase with Improved Pharmacokinetic and Toxicology Characteristics

  摘要：

  Described herein are structure-activity relationships (SARs) of 4-[5-fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]-phenyl]-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (1, CJ-12,918), an imidazole 5-lipoxygenase (5-LO) inhibitor. When I was tested in preclinical studies, cataract formation was observed in rats; however, this compound was metabolized extensively in vivo and showed low systemic exposure. To eliminate this side effect and enhance bioavailability, structural modification was focused on replacing the methoxy group of 1 by modulating lipophilicity (i.e., predicted log D at pH 7.4). The SARs led to the discovery of 4- [5-fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (10, CJ-13,454), which was less lipophilic by 1.2 log D units and showed in vivo potency (ED50 = 4-9 mg/kg) equipotent to 1. Enhanced metabolic stability resulted in fewer in vivo metabolites, as well as improved bioavailability and a better toxicological profile. Thus, 10 was found to be a more practical lead for an orally active 5-LO inhibitor.

  DOI：

  10.1021/jm0303554
• 作为产物：
  描述：

  4-(3-hydroxy-5-fluorophenyl)-4-methylthio-3,4,5,6-tetrahydro-2H-pyran 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以81%的产率得到苯酚,3-氟-5-[四氢-4-(甲磺酰)-2H-吡喃-4-基]-
  参考文献：
  名称：

  4-[5-Fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5,6- tetrahydro-2H-pyran-4-carboxamide, an Orally Active Inhibitor of 5-Lipoxygenase with Improved Pharmacokinetic and Toxicology Characteristics

  摘要：

  Described herein are structure-activity relationships (SARs) of 4-[5-fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]-phenyl]-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (1, CJ-12,918), an imidazole 5-lipoxygenase (5-LO) inhibitor. When I was tested in preclinical studies, cataract formation was observed in rats; however, this compound was metabolized extensively in vivo and showed low systemic exposure. To eliminate this side effect and enhance bioavailability, structural modification was focused on replacing the methoxy group of 1 by modulating lipophilicity (i.e., predicted log D at pH 7.4). The SARs led to the discovery of 4- [5-fluoro-3-[4-(2-methyl-1H-imidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (10, CJ-13,454), which was less lipophilic by 1.2 log D units and showed in vivo potency (ED50 = 4-9 mg/kg) equipotent to 1. Enhanced metabolic stability resulted in fewer in vivo metabolites, as well as improved bioavailability and a better toxicological profile. Thus, 10 was found to be a more practical lead for an orally active 5-LO inhibitor.

  DOI：

  10.1021/jm0303554

文献信息

• US5753682A
  申请人：——

  公开号：US5753682A

  公开（公告）日：1998-05-19