6(S)-methoxymethyl-4-[(4-methoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid | 204129-81-7

• 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: 6(S)-methoxymethyl-4-[(4-methoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid
• CAS: 204129-81-7
• 化学式: C₁₇H₂₅NO₇S₂
• 分子量: 419.52
• InChiKey: IYIVXDDIFYBYQD-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  102.37
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  6(S)-methoxymethyl-4-[(4-methoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxylic acid 在 过氧乙酸 、 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 、 氯仿 为溶剂， 反应 0.5h， 生成 N,6(S)-dihydroxy-4-[(4-methoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-carboxamide 1,1-dioxide
  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：

  methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2(S)-methoxymethoxy-3-hydroxypropyl)-D-penicillamine 在 吡啶 、 三苯基膦 、 lithium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 6(S)-methoxymethyl-4-[(4-methoxyphenyl)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