1-(tert-butyl) 4-methyl-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-1,4-piperidinedicarboxylate | 226398-39-6

• 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-butyl) 4-methyl-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-1,4-piperidinedicarboxylate
• 英文别名: 1-(tert-Butyl) 4-methyl 4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-1,4-piperidinedicarboxylate；1-O-tert-butyl 4-O-methyl 4-[4-(4-chlorophenoxy)phenyl]sulfonylpiperidine-1,4-dicarboxylate
• CAS: 226398-39-6
• 化学式: C₂₄H₂₈ClNO₇S
• 分子量: 510.008
• InChiKey: IMKJOLMUMASYLB-UHFFFAOYSA-N

物化性质

• 沸点：
  617.5±55.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(tert-butyl) 4-methyl-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-1,4-piperidinedicarboxylate 在 N-甲基吗啉 、 lithium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 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：

  4-(4-氯苯氧基)-苯磺酰氯 在 calcium fluoride 、 potassium fluoride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 18.0h， 生成 1-(tert-butyl) 4-methyl-4-{[4-(4-chlorophenoxy)phenyl]sulfonyl}-1,4-piperidinedicarboxylate
  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。
• 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
  作者：Venkatesan Aranapakam、Jamie M. Davis、George T. Grosu、Baker、John Ellingboe、Arie Zask、Jeremy I. Levin、Vincent P. Sandanayaka、Mila Du、Jerauld S. Skotnicki、John F. DiJoseph、Amy Sung、Michele A. Sharr、Loran M. Killar、Thomas Walter、Guixian Jin、Rebecca Cowling、Jeff Tillett、Weiguang Zhao、Joseph McDevitt、Zhang Bao Xu

  DOI：10.1021/jm0205550

  日期：2003.6.1

  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.