(S)-2,2-Dimethyl-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]-[1,4]thiazepane-3-carboxylic acid | 253194-86-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-2,2-Dimethyl-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]-[1,4]thiazepane-3-carboxylic acid
• 英文别名: (3S)-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonyl-1,4-thiazepane-3-carboxylic acid
• CAS: 253194-86-4
• 化学式: C₁₉H₂₂N₂O₅S₂
• 分子量: 422.526
• InChiKey: POZWIXCWCBFTMS-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2,2-Dimethyl-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]-[1,4]thiazepane-3-carboxylic acid 在 草酰氯 、 羟胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 2.0h， 生成 (S)-2,2-Dimethyl-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]-[1,4]thiazepane-3-carboxylic acid hydroxyamide
  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：

  甲基3-巯基-D-缬氨酸酯盐酸盐 在 N-甲基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 141.0h， 生成 (S)-2,2-Dimethyl-4-[4-(pyridin-4-yloxy)-benzenesulfonyl]-[1,4]thiazepane-3-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