methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2-hydroxyethyl)-D-penicillamine | 204141-30-0

• 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-hydroxyethyl)-D-penicillamine
• 英文别名: methyl (2S)-3-(2-hydroxyethylsulfanyl)-2-[(4-methoxyphenyl)sulfonylamino]-3-methylbutanoate
• CAS: 204141-30-0
• 化学式: C₁₅H₂₃NO₆S₂
• 分子量: 377.483
• InChiKey: MBHQFUMIRUYXQK-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2-hydroxyethyl)-D-penicillamine 在 吡啶 、 过氧乙酸 、 草酰氯 、 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 、 氯仿 为溶剂， 反应 8.5h， 生成 (S)-4-(4-Methoxy-benzenesulfonyl)-2,2-dimethyl-1,1-dioxo-1λ⁶-thiomorpholine-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 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2-hydroxyethyl)-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

• [EN] 1,4-HETEROCYCLIC METALLPROTEASE INHIBITORS<br/>[FR] INHIBITEURS 1,4-HETEROCYCLIQUES DE METALLOPROTEASES
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：WO1998008825A1

  公开（公告）日：1998-03-05

  (EN) The invention provides compounds of formula (I) as described in the claims, or an optical isomer, diastereomer or enantiomer thereof, or a pharmaceutically-acceptable salt, or biohydrolyzable amide, ester, or imide thereof are useful as inhibitors of metalloproteases. Also disclosed are pharmaceutical compositions and methods of treating diseases, disorders and conditions characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.(FR) L'invention concerne des composés représentés par la formule (I), tel qu'ils sont décrits dans les revendications, ou un de leurs isomères, diastéréomères ou énantiomères optiques, ou un de leurs sels acceptable sur le plan pharmaceutique, de leurs amides, esters ou imides biohydrolysables, utiles en tant qu'inhibiteurs de métalloprotéases. Elle concerne également des compositions pharmaceutiques et des procédés servant à traiter des maladies, des troubles et des états caractérisés par l'activité de métalloprotéases au moyen de ces composés ou des compositions pharmaceutiques les contenant.

  该发明提供了式(I)的化合物，如权利要求中所述，或其光学异构体、对映异构体或手性异构体，或其药学上可接受的盐，或可生物水解的酰胺、酯或亚酰胺，它们有用作金属蛋白酶抑制剂的作用。还揭示了使用这些化合物或含有它们的药物组合物治疗金属蛋白酶活性引起的疾病、紊乱和病状的方法和药物组合物。
• 1,4-HETEROCYCLIC METALLPROTEASE INHIBITORS
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0923563A1

  公开（公告）日：1999-06-23