3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one | 142853-04-1

• 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: 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one
• 英文别名: 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)propan-1-one；3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)-1-propanone
• CAS: 142853-04-1
• 化学式: C₂₅H₃₂N₂O
• 分子量: 376.542
• InChiKey: JVNVQGLSKUWIEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙基溴苯 、 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 生成 1-[2-(2-Phenylethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl]3-[1-(phenylmethyl)-4-piperidinyl]-1-propanone Dihydrochloride
  参考文献：
  名称：

  Thermogenic composition and benzazepine thermogenics

  摘要：

  本发明的目的是提供一种用于肥胖和肥胖相关疾病或糖尿病的预防和/或治疗药物，其具有降低中枢副作用风险和高普遍性的特点。本发明的另一个目的是提供一种包含以下式的化合物的药物组合物： 其中Ar代表可能被取代和/或缩合的苯基；n代表1到10的整数；R代表氢或可能被取代的碳氢基团，在其n次出现时可能不相同；R可以与Ar或Ar的取代物结合；Y代表可能被取代的氨基或可能被取代的含氮饱和杂环基团，或其盐，可用作热原药剂、抗肥胖药剂、脂肪分解药剂，或肥胖相关疾病的预防和/或治疗药物。

  公开号：

  US06534496B1
• 作为产物：
  描述：

  3-[1-(acetyl)-4-piperidinyl]propionic acid 在 盐酸 、 sodium hydroxide 、 三氯化铝 、 氯化亚砜 、 碘代三甲硅烷 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 57.0h， 生成 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one
  参考文献：
  名称：

  Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles

  摘要：

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.

  DOI：

  10.1039/p19940002993

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
• 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.
• Thermogenic composition and benzazepine thermogenics
  申请人：Takeda Chemical Industries, Inc.

  公开号：US06534496B1

  公开（公告）日：2003-03-18

  The object of the present invention is to provide a prophylactic and/or therapeutic drug for obesity and obesity-associated diseasestor diabetes with a reduced risk for central side effects and high universality in usage. Another object of the present invention is to provide a pharmaceutical composition comprising a compound of the following formula: 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 subsituted 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.

  本发明的目的是提供一种用于肥胖和肥胖相关疾病或糖尿病的预防和/或治疗药物，其具有降低中枢副作用风险和高普遍性的特点。本发明的另一个目的是提供一种包含以下式的化合物的药物组合物： 其中Ar代表可能被取代和/或缩合的苯基；n代表1到10的整数；R代表氢或可能被取代的碳氢基团，在其n次出现时可能不相同；R可以与Ar或Ar的取代物结合；Y代表可能被取代的氨基或可能被取代的含氮饱和杂环基团，或其盐，可用作热原药剂、抗肥胖药剂、脂肪分解药剂，或肥胖相关疾病的预防和/或治疗药物。
• Regioselective Friedel–Crafts acylation of 2,3,4,5-tetrahydro-1H-2-benzazepine and related nitrogen heterocycles
  作者：Yuji Ishihara、Toshimasa Tanaka、Seiji Miwatashi、Akira Fujishima、Giichi Goto

  DOI：10.1039/p19940002993

  日期：——

  It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regioselectivity has been applied to the synthesis of 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitrogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoindolo[2,1-b][2] benzazepin-7-one 9 and 6,7,9,13b-tetrahydro-5H-isoindolo[1,2-a][2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lewis acid coordinated substrates has been used for predicting regioselectivity.