tert-butyl N-[(3S)-1-cycloheptylpyrrolidin-3-yl]carbamate | 1026507-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl N-[(3S)-1-cycloheptylpyrrolidin-3-yl]carbamate
• CAS: 1026507-99-2
• 化学式: C₁₆H₃₀N₂O₂
• 分子量: 282.426
• InChiKey: JFYGAJCAQPVRPX-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(3S)-1-cycloheptylpyrrolidin-3-yl]carbamate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-Bromo-1-methoxy-naphthalene-2-carboxylic acid (1-cycloheptyl-pyrrolidin-3-yl)-amide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Naphthamides as Dopamine D₃ Receptor Ligands

  摘要：

  A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D-2 and D-3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1-alkylpiperidin-4-yl)-4-bromo-1-methoxy-2-naphthamides (1-6), (S)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (7-12), (R)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (13-18), (S)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (19 -25), (R)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (26-31), and N-(9-alkyl-9-azabicyclo-[3.3.1]nonan-3 beta -yl)-4- bromo-1-methoxy-2-naphthamides (32, 33). The results of in vitro radioligand binding studies indicated that the majority of the naphthamide analogues bound with high affinity at both the D-2 and D-3 dopamine receptor subtypes and most of the compounds demonstrated some selectivity for the dopamine D-3 dopamine receptor subtype. These results demonstrated that both the structure of the central amine moiety (piperidine, pyrrolidine, and 9-azabicyclo[3.3.1]nonane) ring and the N-(alkyl) substitution on the amine significantly effects the binding affinity at D-2 and D-3 dopamine receptors. The bulkiness of the N-(1-alkyl) substituent was found to (a) have no effect on pharmacologic selectivity, (b) increase the affinity at Ds receptors, or (c) decrease the affinity at D-2 receptors. The most potent analogue in this series was (S)-N-(1-cycloheptylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamide (10), which had equilibrium dissociation (K-i) values of 1.8 and 0.2 nM for D-2 and D-3 receptors, respectively. The most selective analogue was (R)-N-(1-cycloheptyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamide (30), which had K-i values of 62.8 and 2.4 nM for D-2 and D-3 receptors, respectively. Radioligand binding results for sigma receptors indicated that the structure of the amine moiety and the N-(l-alkyl) substitutions also significantly influence the affinity and selectivity of these compounds at the sigma (1) and sigma (2) sigma receptor subtypes. The two naphthamides containing a 9-azabicyclo[3.3.1]nonan-3 beta -yl central ring were found to be selective for sigma (2) receptors.

  DOI：

  10.1021/jm0100077
• 作为产物：
  描述：

  (S)-3-叔丁氧羰基氨基吡咯烷 、 环庚酮 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以96%的产率得到tert-butyl N-[(3S)-1-cycloheptylpyrrolidin-3-yl]carbamate
  参考文献：
  名称：

  多巴胺D3和D4受体拮抗剂：（S）-（+）-N-（1-苄基-3-吡咯烷基）-5-氯-4-[（环丙基羰基）氨基] -2-的合成与结构-活性关系甲氧基苯甲酰胺（YM-43611）和相关化合物。

  摘要：

  在这项研究中，我们合成了一系列（S）-N-（3-吡咯烷基）苯甲酰胺衍生物1、2a-d，5a-1和7及其对映体（R）-1和（R）- 5c-e，并评估了它们对克隆的多巴胺D2，D3和D4受体的结合亲和力以及它们对阿扑吗啡诱导的小鼠爬山行为的抑制活性。结果表明，D2，D3和D4受体对苯甲酰胺核上4-氨基（R1）的取代基具有不同的体积容忍度（D4> D3> D2），并且可能的是环丙基，环丁基和环戊基羰基在这个系列中，相对于D2受体，D3和D4的亲和力和选择性具有足够的体积。结果还表明，吡咯烷-3-基上的N-取代基（R2）在表达对D2，D3，D4受体和各亚型之间的选择性。化合物之一，（S）-（+）-N-（1-苄基-3-吡咯烷基）-5-氯-4-[（环丙基羰基+ ++）氨基] -2-甲氧基苯甲酰胺（5c）（YM-43611 ）对D3和D4受体表现出高亲和力（Ki值分别为21和2.1 nM），D4选择性比

  DOI：

  10.1021/jm9601720