1-[(4-methoxyphenyl)sulfonyl]-2-hydroxymethyl-hexahydro-1H-azepine | 204129-91-9

• 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: 1-[(4-methoxyphenyl)sulfonyl]-2-hydroxymethyl-hexahydro-1H-azepine
• 英文别名: [1-(4-Methoxyphenyl)sulfonylazepan-2-yl]methanol
• CAS: 204129-91-9
• 化学式: C₁₄H₂₁NO₄S
• 分子量: 299.391
• InChiKey: TYZDHJCIGLVSDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[(4-methoxyphenyl)sulfonyl]-2-hydroxymethyl-hexahydro-1H-azepine 在 jones reagent 、 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 、 丙酮 为溶剂， 反应 0.5h， 生成 N-Hydroxy-1-[(4-methoxyphenyl)sulfonyl]-hexahydro-1H-azepine-2-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：

  7-carboethoxy-tetrahydro-2(3H)-azepinone 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 5.0h， 生成 1-[(4-methoxyphenyl)sulfonyl]-2-hydroxymethyl-hexahydro-1H-azepine
  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

• Heterocyclic metalloprotease inhibitors
  申请人：The Procter & Gamble Company

  公开号：US06166005A1

  公开（公告）日：2000-12-26

  The invention provides compounds of formula ##STR1## 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.

  该发明提供了如下式所示的化合物##STR1##，如权利要求书中所述，或其光学异构体、对映异构体或立体异构体，或其药用可接受盐，或其可生物水解的酰胺、酯或亚酰胺，可用作金属蛋白酶的抑制剂。还披露了利用这些化合物或含有它们的药物组合物来治疗由金属蛋白酶活性特征的疾病、紊乱和病况的方法。
• HETEROCYCLIC METALLOPROTEASE INHIBITORS
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0925287A1

  公开（公告）日：1999-06-30
• US6166005A
  申请人：——

  公开号：US6166005A

  公开（公告）日：2000-12-26
• [EN] HETEROCYCLIC METALLOPROTEASE INHIBITORS<br/>[FR] INHIBITEURS HETEROCYCLIQUES DE METALLOPROTEASES
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：WO1998008827A1

  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 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), tels 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.
• 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.