methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2(S)-methoxymethoxy-3-tert-butyldimethylsiloxypropyl)-D-penicillamine | 253194-99-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2(S)-methoxymethoxy-3-tert-butyldimethylsiloxypropyl)-D-penicillamine
• 英文别名: methyl (2S)-3-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-(methoxymethoxy)propyl]sulfanyl-2-[(4-methoxyphenyl)sulfonylamino]-3-methylbutanoate
• CAS: 253194-99-9
• 化学式: C₂₄H₄₃NO₈S₂Si
• 分子量: 565.825
• InChiKey: LGNAQPFAQWCUNX-FPOVZHCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  36
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2(S)-methoxymethoxy-3-tert-butyldimethylsiloxypropyl)-D-penicillamine 在 吡啶 、 草酰氯 、 四丁基氟化铵 、 羟胺 、 三乙胺 、 N,N-二甲基甲酰胺 、 三苯基膦 、 lithium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 N-hydroxy-6(S)-methoxymethyl-4-[(4-methoxyphenyl)sulfonyl]-2,2-dimethyl-hexahydro-1,4-thiazepine-3(S)-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：

  D-青霉胺 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 22.0h， 生成 methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2(S)-methoxymethoxy-3-tert-butyldimethylsiloxypropyl)-D-penicillamine
  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.