(1S,5S,6R)-7,7-dichloro-5-methyl-2-azabicyclo[4.1.0]heptan-3-one | 586398-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: (1S,5S,6R)-7,7-dichloro-5-methyl-2-azabicyclo[4.1.0]heptan-3-one
• CAS: 586398-57-4
• 化学式: C₇H₉Cl₂NO
• 分子量: 194.061
• InChiKey: BSFLSOHSEYOYFQ-LFRDXLMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  11.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  29.1
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (1S,5S,6R)-7,7-dichloro-5-methyl-2-azabicyclo[4.1.0]heptan-3-one 在 偶氮二异丁腈 、 三苯基氢化锡 、 triethyloxonium fluoroborate 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 4.0h， 生成 ONO-1714
  参考文献：
  名称：

  Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines

  摘要：

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00034-8
• 作为产物：
  描述：

  methyl 3-(R)-methyl-5-hydroxypentanoate 在 sodium hydroxide 、 三氟化硼乙醚 、 三氧化硫吡啶 、 甲基三辛基氯化铵 、 对甲苯磺酸 、 三乙胺 作用下， 以 二甲基亚砜 、 苯甲醚 、 甲苯 为溶剂， 反应 66.0h， 生成 (1S,5S,6R)-7,7-dichloro-5-methyl-2-azabicyclo[4.1.0]heptan-3-one
  参考文献：
  名称：

  Design and Synthesis of Orally Bioavailable Inhibitors of Inducible Nitric Oxide Synthase. Identification of 2-Azabicyclo[4.1.0]heptan-3-imines

  摘要：

  Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00034-8

文献信息

• Condensed piperidine compound
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06110930A1

  公开（公告）日：2000-08-29

  A compound represented by formula (I): ##STR1## wherein all symbols are defined in the specification, or an acid addition salt thereof or a hydrate thereof; a process for preparing the same; and a nitrogen monoxide synthase inhibitor comprising the same as an active ingredient.

  化合物由式(I)表示：##STR1## 其中所有符号在规范中定义，或其酸加盐或水合物；制备该化合物的方法；以及以该化合物作为活性成分的一氧化氮合酶抑制剂。