1-benzyl-4-ethoxycarbonyl-4-(2-oxopiperidino)piperidine | 166180-89-8

• 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: 1-benzyl-4-ethoxycarbonyl-4-(2-oxopiperidino)piperidine
• 英文别名: Ethyl 1-benzyl-4-(2-oxopiperidin-1-yl)piperidine-4-carboxylate
• CAS: 166180-89-8
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: BCYSWMVHYWJAOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-ethoxycarbonyl-4-(2-oxopiperidino)piperidine 在 20percent Pd(OH)2/C 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 11.5h， 生成 1'-[(S)-4-[(3-Cyano-naphthalene-1-carbonyl)-methyl-amino]-3-(3,4-dichloro-phenyl)-butyl]-2-oxo-[1,4']bipiperidinyl-4'-carboxylic acid methylamide
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i
• 作为产物：
  描述：

  5-氯代戊酰氯 在 吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-benzyl-4-ethoxycarbonyl-4-(2-oxopiperidino)piperidine
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i

文献信息

• Heterocyclic compounds
  申请人：ZENECA LIMITED

  公开号：EP0680962A2

  公开（公告）日：1995-11-08

  Compounds of formula I wherein Q1, Q2, Q3, Q4, Q5 and T have any of the meanings given in the specification, their N-oxides, their quaternary ammonium salts, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

  式 I 的化合物 其中 Q1、Q2、Q3、Q4、Q5 和 T 具有说明书中给出的任何含义，它们的 N-氧化物、季铵盐和它们的药学上可接受的盐是神经激肽 A 的非肽拮抗剂，可用于治疗哮喘等。还公开了药物组合物、制备式 I 化合物的工艺和中间体。
• Substituted heterocycles
  申请人：ZENECA LIMITED

  公开号：EP0739891A2

  公开（公告）日：1996-10-30

  Compounds of formula I wherein Q1, Q2, Q3, Q4 and Q5 have any of the meanings given in the specification, their N-oxides, and their pharmacuetically acceptable salts are nonpeptide antagonists NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

  式 I 的化合物 其中 Q1、Q2、Q3、Q4 和 Q5 具有说明书中给出的任何含义，它们的 N-氧化物和它们的药学上可接受的盐是非肽拮抗剂 NKA，可用于治疗哮喘等。还公开了药物组合物、制备式 I 化合物的工艺和中间体。
• NOVEL 4-PIPERIDINYL SUBSTITUTED LACTAMES AS NEUROKININ 2 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF ASTHMA
  申请人：ZENECA LIMITED

  公开号：EP0726893A1

  公开（公告）日：1996-08-21
• CYCLIC AMIDE DERIVATIVES AS NEUROKININ A ANTAGONISTS
  申请人：AstraZeneca AB

  公开号：EP0734383B1

  公开（公告）日：2002-07-24
• US5534525A
  申请人：——

  公开号：US5534525A

  公开（公告）日：1996-07-09