4-[(4-phenoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid | 253194-79-5

• 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: 4-[(4-phenoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid
• 英文别名: (3S)-2,2-dimethyl-4-(4-phenoxyphenyl)sulfonyl-1,4-thiazepane-3-carboxylic acid
• CAS: 253194-79-5
• 化学式: C₂₀H₂₃NO₅S₂
• 分子量: 421.538
• InChiKey: IDSGZFRJVPAFCG-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(4-phenoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid 在 草酰氯 、 羟胺 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-N-hydroxy-2,2-dimethyl-4-(4-phenoxyphenylsulfonyl)-1,4-thiazepane-3-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors

  摘要：

  The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.

  DOI：

  10.1021/jm990330y
• 作为产物：
  描述：

  4-苯氧基苯磺酰氯 在 吡啶 、 三乙胺 、 三苯基膦 、 lithium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 23.0h， 生成 4-[(4-phenoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors

  摘要：

  The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.

  DOI：

  10.1021/jm990330y

文献信息

• Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors
  作者：Neil G. Almstead、Rimma S. Bradley、Stanislaw Pikul、Biswanath De、Michael G. Natchus、Yetunde O. Taiwo、Fei Gu、Lisa E. Williams、Barbara A. Hynd、Michael J. Janusz、C. Michelle Dunaway、Glen E. Mieling

  DOI：10.1021/jm990330y

  日期：1999.11.1

  The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.