N-benzyl-4-(4-tert-butyl-3'-methoxybenzhydryl)piperidine | 255723-95-6

• 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: N-benzyl-4-(4-tert-butyl-3'-methoxybenzhydryl)piperidine
• 英文别名: 1-Benzyl-4-[(4-tert-butylphenyl)-(3-methoxyphenyl)methyl]piperidine
• CAS: 255723-95-6
• 化学式: C₃₀H₃₇NO
• 分子量: 427.63
• InChiKey: LCQLPIVJGWOFLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzyl-4-(4-tert-butyl-3'-methoxybenzhydryl)piperidine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以31%的产率得到3-[(1-Benzyl-piperidin-4-yl)-(4-tert-butyl-phenyl)-methyl]-phenol
  参考文献：
  名称：

  Exploring the Structure−Activity Relationships of [1-(4-tert-Butyl-3‘-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), A High-Affinity and Selective δ-Opioid Receptor Nonpeptide Agonist Ligand

  摘要：

  SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the delta-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation(6). To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the delta-receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.

  DOI：

  10.1021/jm990337f
• 作为产物：
  描述：

  1-苄基-4-哌啶甲醛 在 三氯化铝 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 2.55h， 生成 N-benzyl-4-(4-tert-butyl-3'-methoxybenzhydryl)piperidine
  参考文献：
  名称：

  Exploring the Structure−Activity Relationships of [1-(4-tert-Butyl-3‘-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), A High-Affinity and Selective δ-Opioid Receptor Nonpeptide Agonist Ligand

  摘要：

  SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the delta-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation(6). To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the delta-receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.

  DOI：

  10.1021/jm990337f

文献信息

• Exploring the Structure−Activity Relationships of [1-(4-<i>tert</i>-Butyl-3‘-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), A High-Affinity and Selective δ-Opioid Receptor Nonpeptide Agonist Ligand
  作者：Josue Alfaro-Lopez、Toru Okayama、Keiko Hosohata、Peg Davis、Frank Porreca、Henry I. Yamamura、Victor J. Hruby

  DOI：10.1021/jm990337f

  日期：1999.12.1

  SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the delta-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation(6). To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the delta-receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.