N-[[4-(4-fluorophenoxy)phenyl]methyl]cyclohexanamine | 179056-21-4

• 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: N-[[4-(4-fluorophenoxy)phenyl]methyl]cyclohexanamine
• CAS: 179056-21-4
• 化学式: C₁₉H₂₂FNO
• 分子量: 299.388
• InChiKey: SUYZVLNIODJIKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]carbamate 、 N-[[4-(4-fluorophenoxy)phenyl]methyl]cyclohexanamine 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以87%的产率得到1-Cyclohexyl-1-[4-(4-fluoro-phenoxy)-benzyl]-3-(6-methyl-2,4-bis-methylsulfanyl-pyridin-3-yl)-urea
  参考文献：
  名称：

  Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase. 3. Discovery of a Novel Series of N-Alkyl-N-[(fluorophenoxy)benzyl]-N‘-arylureas with Weak Toxicological Effects on Adrenal Glands

  摘要：

  A series of N-alkyl-N-[(fluorophenoxy)benzyl] -N'-arylureas were prepared and evaluated for their ability to inhibit intestinal acyl-CoA:cholesterol O-acyltransferase and to inhibit accumulation of cholesteryl esters in macrophages in vitro. In vivo hypocholesterolemic activity was assessed in cholesterol-fed rats by oral administration as a dietary admixture and/or by gavage in a PEG400 vehicle. Modification of the alkyl substituent on the N'-aryl moiety and on the urea nitrogen significantly influenced macrophage assay in vitro. Toxicological study revealed a distinct relationship between macrophage assay and the toxicity observed in adrenal glands of rabbits treated with representatives of this series of compounds. Investigations utilizing the macrophage assay as an indicator for adrenal toxicity led to the identification of compounds 1g (FR190809) and 1k (FR186485, or FR195249 as its hydrochloride salt) as potent, nonadrenotoxic, orally efficacious ACAT inhibitors irrespective of the administration method.

  DOI：

  10.1021/jm980399q
• 作为产物：
  描述：

  4-(4-氟苯氧基)苯甲醛 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 生成 N-[[4-(4-fluorophenoxy)phenyl]methyl]cyclohexanamine
  参考文献：
  名称：

  Inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT). Part 1: Identification and structure-activity relationships of a novel series of substituted N-alkyl-N-biphenylylmethyl-N′-arylureas

  摘要：

  A series of N-alkyl-N-biphenylylmethyl-N'-arylurea and related derivatives represented by 1 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Linking of two phenyl groups via oxygen and introduction of fluorine at appropriate positions on the biphenyl moiety improved in vitro and in vivo activity, From this series of analogs, compound 40 (FR179254), which had potent in vitro potency (rabbit intestinal microsomes IC50 = 25 nM), showed excellent plasma cholesterol-lowering activity when administered via the diet (ED50 = 0.045 mg/kg). However, the hypocholesterolemic effect of this compound was moderate when dosed by oral gavage in PEG400 as a vehicle (ED50 = 5.3 mg/kg). Modification of the N'-aryl moiety led to the identification of compound 50 (FR182980) which was efficacious in both dosing models (ED50 = 0.034 mg/kg and 0.11 mg/kg, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10009-8