2,2-dimethyl-3-oxotetradecanoic acid ethyl ester | 150424-05-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 2,2-dimethyl-3-oxotetradecanoic acid ethyl ester
• 英文别名: 2,2-dimethyl-3-oxo-tetradecanoic acid ethyl ester；ethyl 2,2-dimethyl-3-oxotetradecanoate
• CAS: 150424-05-8
• 化学式: C₁₈H₃₄O₃
• 分子量: 298.466
• InChiKey: HISXMYQKMAWFPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  21
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4,6-三甲氧基苯胺 、 2,2-dimethyl-3-oxotetradecanoic acid ethyl ester 在 三甲基铝 作用下， 生成 2,2-dimethyl-3-oxo-N-(2,4,6-trimethoxyphenyl)-tetradecanamide
  参考文献：
  名称：

  Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel .beta.-keto amides as hypocholesterolemic agents

  摘要：

  A study of structure-activity relationships of substituted beta-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the beta-keto group was tolerated with no loss in activity, beta-hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 muM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol-fed rats. Dimethylation alpha to the anilide core(5) and subsequent N-methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).

  DOI：

  10.1021/jm00072a014
• 作为产物：
  描述：

  月桂酰氯 、 异丁酸乙酯 在 lithium diisopropyl amide 作用下， 生成 2,2-dimethyl-3-oxotetradecanoic acid ethyl ester
  参考文献：
  名称：

  Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel .beta.-keto amides as hypocholesterolemic agents

  摘要：

  A study of structure-activity relationships of substituted beta-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the beta-keto group was tolerated with no loss in activity, beta-hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 muM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol-fed rats. Dimethylation alpha to the anilide core(5) and subsequent N-methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).

  DOI：

  10.1021/jm00072a014

文献信息

• Substituted beta-ketoamide ACAT inhibitors
  申请人：Warner-Lambert Company

  公开号：US05278326A1

  公开（公告）日：1994-01-11

  Novel pharmaceutically useful compounds which lower blood cholesterol levels and are beta-ketoamides, oximes, amines, and hydroxyl derivatives thereof.

  一种降低血液胆固醇水平的新型药用化合物，其为β-酮酰胺、肟、胺和其羟基衍生物。
• US5278326A
  申请人：——

  公开号：US5278326A

  公开（公告）日：1994-01-11
• Inhibitors of acyl-CoA:cholesterol acyltransferase. 5. Identification and structure-activity relationships of novel .beta.-keto amides as hypocholesterolemic agents
  作者：Corinne E. Augelli-Szafran、C. John Blankley、Bruce D. Roth、Bharat K. Trivedi、Richard F. Bousley、Arnold D. Essenburg、Katherine L. Hamelehle、Brian R. Krause、Richard L. Stanfield

  DOI：10.1021/jm00072a014

  日期：1993.10

  A study of structure-activity relationships of substituted beta-ketoamide ACAT inhibitors I and II was performed. The results of this study suggest that whereas the beta-keto group was tolerated with no loss in activity, beta-hydroxy and oxime moieties led to significantly reduced activity in vitro and in vivo. The most potent inhibitor from the acyclic series (I) (11, IC50 = 0.006 muM) contained a C-13 alkyl chain. This compound reduced plasma total cholesterol by 38% and 66% at 3 and 30 mg/kg, respectively, in cholesterol-fed rats. Dimethylation alpha to the anilide core(5) and subsequent N-methylation of the amide NH (6) decreased in vitro potency significantly. It was also found that high potency was retained with inhibitors which incorporated the carbonyl into a lactam ring (II).