4-(aminomethyl)-1-benzoylpiperidin-4-ol | 34259-91-1

• 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: 4-(aminomethyl)-1-benzoylpiperidin-4-ol
• 英文别名: 4-Aminomethyl-1-benzoyl-piperidol-(4)；[4-(Aminomethyl)-4-hydroxypiperidin-1-yl]-phenylmethanone
• CAS: 34259-91-1
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: RQVVMNDYFJPKGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(aminomethyl)-1-benzoylpiperidin-4-ol 在 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 生成 phenyl(1-oxa-6-azaspiro[2.5]octan-6-yl)methanone
  参考文献：
  名称：

  Sur l'aptitude à l'extension du noyau pipéridique en fonction de la substitution de l'atome d'azote: réaction du diazométhane avec quelques pipéridones-4 et désamination nitreuse des aminométhyl-alcools correspondants

  摘要：

  在哌啶系列中，环扩张的能力，即环扩张酮与环氧化物的比率，根据氮原子取代基而有很大差异。这个比率在二氮化甲烷对4-哌啶酮的反应和相应氨基醇的亚硝酸脱氨反应中基本相同。对于苯磺酰基而言，这个比率为0.01-0.1，对苯甲酰基则为0.3-0.6左右，对苄基则略大于1。这些差异的原因是电子效应（归结效应和场效应）。这两种反应之间的类比表明，二氮化甲烷对羰基的亲核进攻可以导致环扩张酮和环氧化物的生成。

  DOI：

  10.1139/v71-516
• 作为产物：
  描述：

  phenyl(1-oxa-6-azaspiro[2.5]octan-6-yl)methanone 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4-(aminomethyl)-1-benzoylpiperidin-4-ol
  参考文献：
  名称：

  Novel Pyridylmethylamines as Highly Selective 5-HT_1A Superagonists

  摘要：

  To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, alpha(1), and alpha(2)-adrenergic as well as D-1-D-4 at dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTP gamma S assay. The investigation guided as to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K-i value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

  DOI：

  10.1021/jm100835q

文献信息

• Novel Pyridylmethylamines as Highly Selective 5-HT_1A Superagonists
  作者：Stefan Bollinger、Harald Hübner、Frank W. Heinemann、Karsten Meyer、Peter Gmeiner

  DOI：10.1021/jm100835q

  日期：2010.10.14

  To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, alpha(1), and alpha(2)-adrenergic as well as D-1-D-4 at dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTP gamma S assay. The investigation guided as to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K-i value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.
• Sur l'aptitude à l'extension du noyau pipéridique en fonction de la substitution de l'atome d'azote: réaction du diazométhane avec quelques pipéridones-4 et désamination nitreuse des aminométhyl-alcools correspondants
  作者：H. Favre、Z. Hamlet、R. Lanthier、M. Ménard

  DOI：10.1139/v71-516

  日期：1971.10.1

  Aptitude to ring expansion in the piperidine series, measured by the ratio of ring expanded ketone to epoxide, varies considerably according to the nitrogen atom substituent. This ratio is essentially the same in the case of the reaction of diazomethane on 4-piperidones and the nitrous acid deamination of the corresponding aminoalcohols. The values of the ratio are 0.01–0.1 for a phenylsulfonyl group, of the order 0.3–0.6 for a benzoyl group and slightly greater than 1 for a benzyl group. Electronic effects (inductive and field effects) are the cause of these differences. Parallels between the two reactions indicate that nucleophilic attack of diazomethane on the carbonyl group can lead to the ring expanded ketone and the epoxide.

  在哌啶系列中，环扩张的能力，即环扩张酮与环氧化物的比率，根据氮原子取代基而有很大差异。这个比率在二氮化甲烷对4-哌啶酮的反应和相应氨基醇的亚硝酸脱氨反应中基本相同。对于苯磺酰基而言，这个比率为0.01-0.1，对苯甲酰基则为0.3-0.6左右，对苄基则略大于1。这些差异的原因是电子效应（归结效应和场效应）。这两种反应之间的类比表明，二氮化甲烷对羰基的亲核进攻可以导致环扩张酮和环氧化物的生成。