1-O-tert-butyl 4-O-ethyl 4-(4-but-2-ynoxyphenyl)sulfanylpiperidine-1,4-dicarboxylate | 1025986-88-2

• 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: 1-O-tert-butyl 4-O-ethyl 4-(4-but-2-ynoxyphenyl)sulfanylpiperidine-1,4-dicarboxylate
• CAS: 1025986-88-2
• 化学式: C₂₃H₃₁NO₅S
• 分子量: 433.569
• InChiKey: CWTPXHBVRVZHBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-O-tert-butyl 4-O-ethyl 4-(4-but-2-ynoxyphenyl)sulfanylpiperidine-1,4-dicarboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-(4-But-2-ynoxyphenyl)sulfanyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x
• 作为产物：
  描述：

  4-but-2-ynyloxybenzenesulfonyl chloride 在 盐酸 、 叔丁基锂 、 N,N-二甲基甲酰胺 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 22.17h， 生成 1-O-tert-butyl 4-O-ethyl 4-(4-but-2-ynoxyphenyl)sulfanylpiperidine-1,4-dicarboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x

文献信息

• Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors
  作者：Aranapakam M. Venkatesan、Jamie M. Davis、George T. Grosu、Jannie Baker、Arie Zask、Jeremy I. Levin、John Ellingboe、Jerauld S. Skotnicki、John F. DiJoseph、Amy Sung、Guixian Jin、Weixin Xu、Diane Joseph McCarthy、Dauphine Barone

  DOI：10.1021/jm040086x

  日期：2004.12.1

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.