((R)-1-cyclohexylpyrrolidin-2-yl)methanamine | 259538-87-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ((R)-1-cyclohexylpyrrolidin-2-yl)methanamine
• 英文别名: [(2 R)-1-Cyclohexylpyrrolidinyl]methylamine；[(2R)-1-cyclohexylpyrrolidinyl]methylamine；[(2R)-1-cyclohexylpyrrolidin-2-yl]methanamine
• CAS: 259538-87-9
• 化学式: C₁₁H₂₂N₂
• 分子量: 182.309
• InChiKey: FWZCSDNSXJJNLH-LLVKDONJSA-N

物化性质

• 沸点：
  244.3±8.0 °C(Predicted)
• 密度：
  0.987±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Brom-1-methoxynaphthalin-2-carbonsaeurechlorid 、 ((R)-1-cyclohexylpyrrolidin-2-yl)methanamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-Bromo-1-methoxy-naphthalene-2-carboxylic acid ((R)-1-cyclohexyl-pyrrolidin-2-ylmethyl)-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：

  (R)-N-(1-benzyl-2-pyrrolidinylmethyl)-tert-butoxycarbamide 在 5percent Pd/C 氢气 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 13.0h， 生成 ((R)-1-cyclohexylpyrrolidin-2-yl)methanamine
  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

文献信息

• Antithrombotic agents
  申请人：PFIZER INC.

  公开号：EP0997474B1

  公开（公告）日：2003-10-29
• Synthesis and Nicotinic Receptor Activity of Chemical Space Analogues of <i>N</i>-(3<i>R</i>)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) and 1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic Acid 4-Bromophenyl Ester (SSR180711)
  作者：Lise Bréthous、Noemi Garcia-Delgado、Julian Schwartz、Sonia Bertrand、Daniel Bertrand、Jean-Louis Reymond

  DOI：10.1021/jm300030r

  日期：2012.5.24

  The Chemical Universe Generated Databases up to 11 atoms of CNOF (GDB-11) and up to 13 atoms of CNOClS (GDB-13) were used to enumerate analogues of the diamine part of two known alpha 7 nicotinic receptor agonists and construct libraries of virtual analogues of these drugs. The libraries were scored using structure-based (docking to the nicotine binding site of the acetylcholine binding protein 1uw6.pdb) or ligand-based (similarity to the parent drugs) methods, and the top-scoring virtual ligands were inspected for easily accessible synthetic targets. In total, 21 diamines were prepared and acylated with aromatic carboxylic or oxycarbonic acids to produce 85 analogues of the parent drugs. The compounds were profiled by electrophysiology in Xenopus oocytes expressing human nicotinic acetylcholine receptor (nAChR) subtypes alpha 7, alpha 3 beta 2, alpha 4 beta 2, alpha 3 beta 4, or alpha 4 beta 4. Characterization of selected compounds revealed eight inhibitors of the alpha 7 nicotinic receptor and three positive allosteric modulators of the alpha 3 beta 2 nAChR.
• US6180627
  申请人：——

  公开号：——

  公开（公告）日：——
• US06180627B2
  申请人：——

  公开号：——

  公开（公告）日：——
• US6180627B1
  申请人：——

  公开号：US6180627B1

  公开（公告）日：2001-01-30