4-Amino-5-chloro-2,3-pentamethylenequinoline | 122994-75-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-Amino-5-chloro-2,3-pentamethylenequinoline
• 英文别名: 6H-Cyclohepta[b]quinolin-11-amine, 1-chloro-7,8,9,10-tetrahydro-；1-chloro-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine
• CAS: 122994-75-6
• 化学式: C₁₄H₁₅ClN₂
• 分子量: 246.739
• InChiKey: KAAAIHLOSOSBCH-UHFFFAOYSA-N

物化性质

• 沸点：
  449.6±45.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Amino-5-chloro-2,3-pentamethylenequinoline 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(5-{[(1-chloro-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-yl)amino]methyl}thien-2-yl)-2,2,2-trifluoroethanone
  参考文献：
  名称：

  A Structure-Based Design Approach to the Development of Novel, Reversible AChE Inhibitors

  摘要：

  Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.

  DOI：

  10.1021/jm010826r
• 作为产物：
  描述：

  2-氨基-6-氯苯甲腈 、 环庚酮 以11%的产率得到4-Amino-5-chloro-2,3-pentamethylenequinoline
  参考文献：
  名称：

  Certain 9-amino-2-(or 4)-oxa 1,2,3,4-tetrahydro- or

  摘要：

  从由9-氨基-4-氧杂-1,2,3,4-四氢吖啶、9-氨基-2-氧杂-1,2,3,4-四氢吖啶、9-氨基-8-氟-4-氧杂-1,2,3,4-四氢吖啶、9-氨基-4-氧杂-1,2,3,4,5,6,7,8-八氢吖啶或其药物可接受盐组成的组中选出的化合物，用于治疗阿尔茨海默病是有用的。

  公开号：

  US05202440A1

文献信息

• Certain 9-amino-2-(or 4)-oxa 1,2,3,4-tetrahydro- or
  申请人：Pfizer Inc.

  公开号：US05202440A1

  公开（公告）日：1993-04-13

  Compounds selected from the group consisting of 9-amino-4-oxa-1,2,3,4-tetrahydro-acridine, 9-amino-2-oxa-1,2,3,4-tetrahydro-acridine, 9-amino-8-fluoro-4-oxa-1,2,3,4-tetrahydro-acridine, 9-amino-4-oxa-1,2,3,4,5,6,7,8-octahydro-acridine or a pharmaceutical acceptable salt thereof are useful treating Alzheimer's disease.

  从由9-氨基-4-氧杂-1,2,3,4-四氢吖啶、9-氨基-2-氧杂-1,2,3,4-四氢吖啶、9-氨基-8-氟-4-氧杂-1,2,3,4-四氢吖啶、9-氨基-4-氧杂-1,2,3,4,5,6,7,8-八氢吖啶或其药物可接受盐组成的组中选出的化合物，用于治疗阿尔茨海默病是有用的。
• 4-aminopyridine derivatives
  申请人：PFIZER INC.

  公开号：EP0311303A2

  公开（公告）日：1989-04-12

  Compounds of the formula wherein A, B, R¹ and R² are defined below. The above compounds inhibit brain acetylcholine­sterase and are useful in the treatment of Alzheimer's disease.

  式中的化合物 其中 A、B、R¹ 和 R² 的定义如下。 上述化合物能抑制脑乙酰胆碱酯酶，可用于治疗阿尔茨海默氏症。
• US5202440A
  申请人：——

  公开号：US5202440A

  公开（公告）日：1993-04-13
• [EN] 4-AMINOPYRIDINE DERIVATIVES
  申请人：PFIZER INC.

  公开号：WO1989002740A1

  公开（公告）日：1989-04-06

  (EN) Compounds of formula (I), wherein R1, R2, A and B are defined hereinbelow. The compounds of the present invention inhibit brain acetylcholinesterase and are useful in the treatment of Alzheimer's disease.(FR) Des composés de formule (I) où R1, R2, A et B ont la notation ci-après, inhibent l'acétylcholinestérase cérébrale et sont utiles dans le traitement de la maladie d'Alzheimer.
• A Structure-Based Design Approach to the Development of Novel, Reversible AChE Inhibitors
  作者：Caroline Doucet-Personeni、Philip D. Bentley、Rodney J. Fletcher、Adrian Kinkaid、Gitay Kryger、Bernard Pirard、Anne Taylor、Robin Taylor、John Taylor、Russell Viner、Israel Silman、Joel L. Sussman、Harry M. Greenblatt、Terence Lewis

  DOI：10.1021/jm010826r

  日期：2001.9.1

  Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.