2-hydroxymethyl-3,3-dimethyl-hexahydro-1H-azepine | 204129-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 2-hydroxymethyl-3,3-dimethyl-hexahydro-1H-azepine
• 英文别名: (3,3-Dimethylazepan-2-yl)methanol
• CAS: 204129-87-3
• 化学式: C₉H₁₉NO
• 分子量: 157.256
• InChiKey: ISWDJGIFAUXNOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-hydroxymethyl-3,3-dimethyl-hexahydro-1H-azepine 在 jones reagent 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 0.5h， 生成 1-[(4-methoxyphenyl)sulfonyl]-3,3-dimethyl-hexahydro-1H-azepine-2-carboxylic acid chloride
  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：

  6,6-dimethyl-7-carbomethoxy-tetrahydro-2(3H)-azepinone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2-hydroxymethyl-3,3-dimethyl-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：US20030186958A1

  公开（公告）日：2003-10-02

  The invention provides compounds of formula 1 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.

  本发明提供了式 1 的化合物 1 或其光学异构体、非对映异构体或对映体，或其药学上可接受的盐，或其生物可水解的酰胺、酯或亚胺，可作为金属蛋白酶的抑制剂。 此外，还公开了使用这些化合物或含有这些化合物的药物组合物治疗以金属蛋白酶活性为特征的疾病、失调和病症的药物组合物和方法。
• 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
• US6545038B1
  申请人：——

  公开号：US6545038B1

  公开（公告）日：2003-04-08
• [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.