1-(tert-butoxycarbonyl)-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-4-piperidine carboxylic acid | 352209-78-0

• 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: 1-(tert-butoxycarbonyl)-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-4-piperidine carboxylic acid
• 英文别名: 4-[4-(4-Chlorophenoxy)phenyl]sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid
• CAS: 352209-78-0
• 化学式: C₂₃H₂₆ClNO₇S
• 分子量: 495.981
• InChiKey: PBODIKNFUJQOAL-UHFFFAOYSA-N

物化性质

• 沸点：
  659.3±55.0 °C(Predicted)
• 密度：
  1.358±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-4-piperidine carboxylic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 羟胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以41%的产率得到1-(tert-butyl) 4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-4-[(hydroxyamino)carbonyl]-1-piperidine carboxylate
  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：

  N-Boc-4-哌啶甲酸甲酯 在 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 15.0h， 生成 1-(tert-butoxycarbonyl)-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-4-piperidine 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

文献信息

• Method for preparing alpha-sulfonyl hydroxamic acid derivatives
  申请人：——

  公开号：US20020099035A1

  公开（公告）日：2002-07-25

  Compounds of the formula: 1 that can be important as matrix metalloproteinase (MMP) and TNF-alpha converting enzyme (TACE) inhibitors, phosphodiesterase inhibitors, renin inhibitors, antithrombotics, and 5 -lipoxygenase inhibitors are prepared by novel methods of the present invention.

  该公式的化合物： 可以作为基质金属蛋白酶（MMP）和TNF-alpha转化酶（TACE）抑制剂、磷酸二酯酶抑制剂、肾素抑制剂、抗血栓药物和5-脂氧合酶抑制剂的重要化合物，通过本发明的新方法制备。