1methyl-7-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-1,2,3,4-tetrahydroquinoline | 142852-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1methyl-7-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-1,2,3,4-tetrahydroquinoline
• 英文别名: 3-(1-Benzylpiperidin-4-yl)-1-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)propan-1-one；3-(1-benzylpiperidin-4-yl)-1-(1-methyl-3,4-dihydro-2H-quinolin-7-yl)propan-1-one
• CAS: 142852-00-4
• 化学式: C₂₅H₃₂N₂O
• 分子量: 376.542
• InChiKey: BWZUHISSAMBGLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1methyl-7-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-1,2,3,4-tetrahydroquinoline 生成 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one dihydrochloride
  参考文献：
  名称：

  Condensed heterocyclic compounds, their production and use

  摘要：

  化学式（I）的一种缩合杂环衍生物：##STR1##其中X是氧原子、硫原子或R.sup.1--N<，其中R.sup.1是氢原子、可能被取代的碳氢基团或可能被取代的酰基团；R.sup.2是氢原子或可能被取代的碳氢基团；环A是可能被取代的苯环，k是0到3的整数；m是1到8的整数；n是1到6的整数，或其药学上可接受的盐，具有高胆碱酯酶抑制活性，并提供其制备方法。

  公开号：

  US05273974A1
• 作为产物：
  描述：

  3-(1-acetyl-4-piperidinyl)propionyl chloride 在 盐酸 、 三氯化铝 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 95.17h， 生成 1methyl-7-[1-oxo-3-[1-(phenylmethyl)piperidin-4-yl]propyl]-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  Central Cholinergic Agents. 6. Synthesis and Evaluation of 3-[1-(Phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)- 1-propanones and Their Analogs as Central Selective Acetylcholinesterase Inhibitors

  摘要：

  In an attempt to find central selective acetylcholinesterase (AChE) inhibitors, 3-[1-(phenyl-methyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanones 9 and their analogs were designed on the basis of our working hypothesis of the enzyme's active site. These compounds were prepared by regioselective Friedel-Crafts acylation of 2,3,4,5-tetrahydro-1H-benzazepines and related nitrogen heterocycles as a key step. Most compounds showed potent inhibitory activities with IC(50)s in the 10-300 nM range. In order to estimate their central selectivities, we examined their effects on the apomorphine-induced circling behavior in rats with unilateral striatal lesions. Among compounds with potent AChE inhibition, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (9a, TAK-147) (IC50 of AChE inhibition = 97.7 nM) inhibited the circling behavior at 3 mg/kg po, in which it had no significant effect on peripheral cholinergic effects. This demonstrates that 9a has favorable central selectivity. Furthermore, 9a significantly ameliorated diazepam-induced passive avoidance deficit at 1 mg/kg po. The benzazepine derivative 9a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm00041a007

文献信息

• THERMOGENIC COMPOSITION AND BENZAZEPINE THERMOGENICS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0975624A1

  公开（公告）日：2000-02-02
• NEUROGENESIS BY MUSCARINIC RECEPTOR MODULATION
  申请人：Barlow Carrolee

  公开号：US20110319386A1

  公开（公告）日：2011-12-29

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on muscarinic receptor modulation, such as via inhibition of acetylcholine esterase (AChE) activity, alone or in combination with another neurogenic agent to stimulate or activate the formation of new nerve cells.
• US5273974A
  申请人：——

  公开号：US5273974A

  公开（公告）日：1993-12-28
• US6534496B1
  申请人：——

  公开号：US6534496B1

  公开（公告）日：2003-03-18
• [EN] THERMOGENIC COMPOSITION AND BENZAZEPINE THERMOGENICS<br/>[FR] COMPOSITION THERMOGENIQUE ET COMPOSES THERMOGENIQUES A BASE DE BENZAZEPINE
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1998046590A1

  公开（公告）日：1998-10-22

  (EN) The object of the present invention is to provide a prophylactic and/or therapeutic drug for obesity and obesity-associated diseases or diabetes with a reduced risk for central side effects and high universality in usage. Another object of the present inventio is to provide a pharmaceutical composition comprising a compound of formula (I), wherein Ar represents phenyl which may be substituted and/or condensed; n represents an integer of 1 to 10; R represents hydrogen or a hydrocarbon group which may be substituted, which may not be the same in its n occurrences; R may be bound to either Ar or a substituent for Ar; Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof, which can be used for a thermogenic agent, an antiobesity agent, a lipolytic agent, or a prophylactic and/or treating drug for obesity-associated diseases.(FR) L'invention concerne un médicament prophylactique et/ou thérapeutique pour traiter l'obésité et les maladies liées à l'obésité, ou le diabète, avec une réduction des risques de réactions secondaires centrales et une grande universalité d'utilisation. L'invention concerne aussi une composition pharmaceutique comprenant un composé de formule (I). Dans ladite formule, Ar représente phényle, pouvant être substitué et/ou condensé; n représente un entier de 1 à 10; R est hydrogène, ou un groupe hydrocarbure pouvant être substitué et pouvant être différent quant aux occurrences n; R peut être lié à Ar ou à un élément de substitution à Ar; Y représente un groupe amino pouvant être substitué ou un groupe hétérocyclique saturé contenant de l'azote, qui peut être substitué, ou un sel correspondant. Ladite composition peut être utilisée comme agent thermogénique, agent contre l'obésité, agent lipolytique, ou médicament prophylactique et/ou curatif pour traiter les maladies liées à l'obésité.