(SR)-2-[(RS)-4-but-2-ynyloxyphenylsulfinyl]-2-phenyl-N-hydroxyacetamide

• 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: (SR)-2-[(RS)-4-but-2-ynyloxyphenylsulfinyl]-2-phenyl-N-hydroxyacetamide
• 英文别名: (2S)-2-[(R)-(4-but-2-ynoxyphenyl)sulfinyl]-N-hydroxy-2-phenylacetamide
• 化学式: C₁₈H₁₇NO₄S
• 分子量: 343.403
• InChiKey: LMLJZJGMFKPKNY-XDHUDOTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  94.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  α-溴苯乙酸乙酯 在 sodium hydroxide 、 草酰氯 、 盐酸羟胺 、 双氧水 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 丙酮 、 乙腈 为溶剂， 生成 (SR)-2-[(RS)-4-but-2-ynyloxyphenylsulfinyl]-2-phenyl-N-hydroxyacetamide
  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.