(1R)-3-[(5S,8S)-8-benzhydryl-1,4-diazabicyclo[3.3.1]nonan-4-yl]-1-(4-fluorophenyl)propan-1-ol | 1028809-53-1

• 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: (1R)-3-[(5S,8S)-8-benzhydryl-1,4-diazabicyclo[3.3.1]nonan-4-yl]-1-(4-fluorophenyl)propan-1-ol
• CAS: 1028809-53-1
• 化学式: C₂₉H₃₃FN₂O
• 分子量: 444.592
• InChiKey: GAKAYJNKCDLKCE-HZFUHODCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-((1S,6S)-6-benzhydryl-2,5-diazabicyclo[3.3.1]nonane-2-yl)-1-(4-fluorophenyl)propyl-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以90%的产率得到(1R)-3-[(5S,8S)-8-benzhydryl-1,4-diazabicyclo[3.3.1]nonan-4-yl]-1-(4-fluorophenyl)propan-1-ol
  参考文献：
  名称：

  Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: Interaction with dopamine, serotonin, and norepinephrine transporters

  摘要：

  Our earlier effort to develop constrained analogues of flexible piperidine derivatives for monoamine transporters led to the development of a series of 3,6-disubstituted piperidine derivatives, and a series of 4,8-disubstituted 1,4-diazabicyclo[3.3.1]nonane derivatives. In further structure-activity relationship (SAR) studies on these constrained derivatives, several novel analogues were developed where an exocyclic hydroxyl group was introduced on the N-alkyl-aryl side chain. All synthesized derivatives were tested for their affinities for the dopamine transporter (DAT), serotonin (5-HT) transporter (SERT), and norepinephrine transporter (NET) in the brain by measuring their potency in inhibiting the uptake of [H-3]DA, [H-3]5-HT, and [H-3]NE, respectively. Compounds were also tested for their binding potency at the DAT by their ability to inhibit binding of [H-3]WIN 35,428. The results indicated that position of the hydroxyl group on the N-alkyl side chain is important along with the length of the side chain. In general, hydroxyl derivatives derived from more constrained bicyclic diamines exhibited greater selectivity for interaction with DAT compared to the corresponding 3,6-disubstituted diamines. In the current series of molecules, compound 11b with N-propyl side chain with the hydroxyl group attached in the benzylic position was the most potent and selective for DAT (K-i = 8.63 nM; SERT/DAT = 172 and NET/DAT = 48.4). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.01.009

文献信息

• N- AND O-SUBSTITUED 4-[2-(DIPHENYLMETHOXY)-ETHYL]-1-[(PHENYL)METHYL]PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH
  申请人：Dutta Aloke K.

  公开号：US20080182991A1

  公开（公告）日：2008-07-31

  N- and O-substituted 4[2-diaromaticmethoxy and methylamino)alkyl] piperidines exhibit high CNS activity with respect to the dopamine transporter (DAT) and serotonin transporter (SERT). Preferred compounds exhibit highly differential behavior as between the DAT and SERT and between the DAT and the norepinephrine transporter (NET). The compounds have utility in treating CNS disorders, including but not limited to cocaine addiction, depression, and Parkinson's disease.

  N-和O-取代的4-[2-二芳基甲氧基和甲基氨基)烷基]哌啶表现出高中枢神经系统活性，与多巴胺转运体（DAT）和5-羟色胺转运体（SERT）有关。优选化合物在DAT和SERT以及DAT和去甲肾上腺素转运体（NET）之间表现出高度差异行为。这些化合物在治疗中枢神经系统疾病方面具有实用价值，包括但不限于可卡因成瘾、抑郁症和帕金森病。
• US8211916B2
  申请人：——

  公开号：US8211916B2

  公开（公告）日：2012-07-03