Azepan-1-yl-[4-[chloro-(3-methoxyphenyl)methyl]phenyl]methanone | 192521-11-2

• 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: Azepan-1-yl-[4-[chloro-(3-methoxyphenyl)methyl]phenyl]methanone
• CAS: 192521-11-2
• 化学式: C₂₁H₂₄ClNO₂
• 分子量: 357.88
• InChiKey: HFYNJZKZYLYLAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2R,5S)-1-烯丙基-2,5-二甲基哌嗪 、 Azepan-1-yl-[4-[chloro-(3-methoxyphenyl)methyl]phenyl]methanone 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 15.0h， 生成 {4-[(R)-((2S,5R)-4-Allyl-2,5-dimethyl-piperazin-1-yl)-(3-methoxy-phenyl)-methyl]-phenyl}-azepan-1-yl-methanone 、 {4-[(S)-((2S,5R)-4-Allyl-2,5-dimethyl-piperazin-1-yl)-(3-methoxy-phenyl)-methyl]-phenyl}-azepan-1-yl-methanone
  参考文献：
  名称：

  Probes for Narcotic Receptor-Mediated Phenomena. 25. Synthesis and Evaluation of N-Alkyl-Substituted (α-Piperazinylbenzyl)benzamides as Novel, Highly Selective δ Opioid Receptor Agonists

  摘要：

  A series of N-alkyl- and N,N-dialkyl-4-[alpha-{(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively.

  DOI：

  10.1021/jm970106d
• 作为产物：
  描述：

  4-(3’-甲氧基苯甲酰基)苯甲酸 在 盐酸 、 sodium tetrahydroborate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 Azepan-1-yl-[4-[chloro-(3-methoxyphenyl)methyl]phenyl]methanone
  参考文献：
  名称：

  Probes for Narcotic Receptor-Mediated Phenomena. 25. Synthesis and Evaluation of N-Alkyl-Substituted (α-Piperazinylbenzyl)benzamides as Novel, Highly Selective δ Opioid Receptor Agonists

  摘要：

  A series of N-alkyl- and N,N-dialkyl-4-[alpha-{(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively.

  DOI：

  10.1021/jm970106d