1-benzyloxycarbonyl-4-carboxy-4-(2-oxopiperidino)piperidine | 166180-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-benzyloxycarbonyl-4-carboxy-4-(2-oxopiperidino)piperidine
• 英文别名: 4-(2-oxopiperidin-1-yl)-1-phenylmethoxycarbonylpiperidine-4-carboxylic acid
• CAS: 166180-94-5
• 化学式: C₁₉H₂₄N₂O₅
• 分子量: 360.41
• InChiKey: BRIZVRFVUVROQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  587.1±50.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-benzyloxycarbonyl-4-carboxy-4-(2-oxopiperidino)piperidine 在 20percent Pd(OH)2/C 4-二甲氨基吡啶 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 4-methylaminocarbonyl-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
• 作为产物：
  描述：

  5-氯代戊酰氯 在 20percent Pd(OH)2/C 吡啶 、 sodium hydroxide 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 11.5h， 生成 1-benzyloxycarbonyl-4-carboxy-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

• Cyclic amide derivatives for treating asthma
  申请人：Zeneca Limited

  公开号：US05589489A1

  公开（公告）日：1996-12-31

  Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, 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##STR1##其中Q.sup.1、Q.sup.2、Q.sup.3和Q.sup.4具有规范中给定的任意含义，它们的N-氧化物以及它们的药用盐是神经激肽A的非肽拮抗剂，可用于治疗哮喘等。还公开了制药组合物、制备式I化合物和中间体的方法。
• Piperidine derivatives useful as neurokinin antagonists
  申请人：Zeneca Limited

  公开号：US05635509A1

  公开（公告）日：1997-06-03

  Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, 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##STR1##其中Q.sup.1、Q.sup.2、Q.sup.3和Q.sup.4具有规范中给定的任何含义，它们的N-氧化物以及它们的药用盐是神经激肽A的非肽类拮抗剂，用于治疗哮喘等。还公开了制药组合物、制备式I化合物和中间体的方法。
• Lactam derivatives
  申请人：Zeneca Limited

  公开号：US05534525A1

  公开（公告）日：1996-07-09

  Compounds of formula I ##STR1## wherein J, B, L, X, m and M have any of the meanings given in the specification, their N-oxides, 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.

  式子I的化合物 ##STR1## 其中J，B，L，X，m和M具有规范中给出的任何含义，它们的N-氧化物和其药学上可接受的盐是神经激肽A的非肽拮抗剂，并可用于治疗哮喘等疾病。还披露了制药组合物，制备式I化合物的过程以及中间体。
• Lactam compounds which are useful in the treatment of asthma
  申请人：Zeneca Limited

  公开号：US05677317A1

  公开（公告）日：1997-10-14

  Compounds of formula I ##STR1## wherein J, B, L, X, m and M have any of the meanings given in the specification, their N-oxides, 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 ##STR1## 其中J、B、L、X、m和M的含义可以是规范中给出的任何含义，它们的N-氧化物和药学上可接受的盐是神经激肽A的非肽拮抗剂，可用于治疗哮喘等疾病。还公开了制药组合物、制备式I化合物和中间体的方法。
• Compounds and method for the treatment of overactive bladder
  申请人：Bialecki Russell

  公开号：US20050203113A1

  公开（公告）日：2005-09-15

  NK2R binding compounds in accord with structural diagram I useful for the treatment or prevention of OAB or UI in mammals, particularly humans are disclosed: wherein in said compounds D, A, R 1 , R 3 and R 4 are as defined in the specification. Pharmaceutically-advantageous salts of the compounds, methods of use of the compounds, either alone or in combination with other pharmacological agents, and pharmaceutical compositions useful in practicing the methods of the invention are also disclosed.

  本发明揭示了符合结构图I的NK2R结合化合物，用于治疗或预防哺乳动物，特别是人类的OAB或UI，其中在该化合物中，D，A，R1，R3和R4如规范中所定义。本发明还揭示了该化合物的制药有利盐、使用该化合物的方法，无论是单独使用还是与其他药理学制剂联合使用，以及在实施本发明的方法中有用的制药组合物。