4-(4-butoxybenzenesulfonyl)-1-[3-(2-morpholin-1-ylethoxy)benzyl]piperidine-4-carboxylic acid ethyl ester | 239797-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-butoxybenzenesulfonyl)-1-[3-(2-morpholin-1-ylethoxy)benzyl]piperidine-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 4-(4-butoxyphenyl)sulfonyl-1-[[3-(2-morpholin-4-ylethoxy)phenyl]methyl]piperidine-4-carboxylate
• CAS: 239797-36-5
• 化学式: C₃₁H₄₄N₂O₇S
• 分子量: 588.766
• InChiKey: JNWWKZBFSKOILR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(4-butoxybenzenesulfonyl)-1-[3-(2-morpholin-1-ylethoxy)benzyl]piperidine-4-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 72.0h， 以85%的产率得到4-(4-butoxybenzenesulfonyl)-1-[3-(2-morpholin-1-ylethoxy)benzyl]piperidine-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of N-Substituted 4-Arylsulfonylpiperidine-4-hydroxamic Acids as Novel, Orally Active Matrix Metalloproteinase Inhibitors for the Treatment of Osteoarthritis

  摘要：

  The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.

  DOI：

  10.1021/jm0205550
• 作为产物：
  描述：

  bis(2-hydroxyethyl)-[3-(2-morpholin-1-ylethoxy)benzyl]amine hydrochloride 在 氯化亚砜 、 18-冠醚-6 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 17.0h， 生成 4-(4-butoxybenzenesulfonyl)-1-[3-(2-morpholin-1-ylethoxy)benzyl]piperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of N-Substituted 4-Arylsulfonylpiperidine-4-hydroxamic Acids as Novel, Orally Active Matrix Metalloproteinase Inhibitors for the Treatment of Osteoarthritis

  摘要：

  The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.

  DOI：

  10.1021/jm0205550