3-(2-Chloro-4-methanesulfonyl-6-methyl-pyridin-3-yl)-1-cycloheptyl-1-[4-(4-fluoro-phenoxy)-benzyl]-urea | 215589-64-3

• 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: 3-(2-Chloro-4-methanesulfonyl-6-methyl-pyridin-3-yl)-1-cycloheptyl-1-[4-(4-fluoro-phenoxy)-benzyl]-urea
• 英文别名: 3-(2-chloro-6-methyl-4-methylsulfonylpyridin-3-yl)-1-cycloheptyl-1-[[4-(4-fluorophenoxy)phenyl]methyl]urea
• CAS: 215589-64-3
• 化学式: C₂₈H₃₁ClFN₃O₄S
• 分子量: 560.089
• InChiKey: FWJYMSWCKJMBRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-chloro-6-methyl-4-(methylthio)-3-nitropyridine 在 镍 氢气 、 N,N-二甲基苯胺 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0~100.0 ℃ 、101.33 kPa 条件下， 反应 11.0h， 生成 3-(2-Chloro-4-methanesulfonyl-6-methyl-pyridin-3-yl)-1-cycloheptyl-1-[4-(4-fluoro-phenoxy)-benzyl]-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

文献信息

• Inhibitors of Acyl-CoA:Cholesterol <i>O</i>-Acyltransferase. 3. Discovery of a Novel Series of <i>N</i>-Alkyl-<i>N</i>-[(fluorophenoxy)benzyl]-<i>N</i>‘-arylureas with Weak Toxicological Effects on Adrenal Glands
  作者：Akira Tanaka、Takeshi Terasawa、Hiroyuki Hagihara、Noriko Ishibe、Masae Sawada、Yuri Sakuma、Masaharu Hashimoto、Hisashi Takasugi、Hirokazu Tanaka

  DOI：10.1021/jm980399q

  日期：1998.10.1

  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.