cis-6-benzhydrylpiperidin-3-ylamine

• 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: cis-6-benzhydrylpiperidin-3-ylamine
• 英文别名: (-)-cis-6-Benzhydrylpiperidin-3-ylamine；(3S,6S)-6-benzhydrylpiperidin-3-amine
• 化学式: C₁₈H₂₂N₂
• 分子量: 266.386
• InChiKey: KPNXZZXQPSJJQN-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cis-6-benzhydrylpiperidin-3-ylamine 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 生成 (-)-(S,S)-cis-4-[(6-benzhydrylpiperidin-3-ylamino)methyl]benzonitrile
  参考文献：
  名称：

  顺式-（6-苯甲酰基哌啶-3-基）苄胺类似物与单胺转运蛋白的相互作用：（2,2-二苯乙基）-[1-（4-氟苄基）结构受约束的3,6-二取代哌啶类似物的结构-活性关系研究）哌啶-4-基甲基]胺。

  摘要：

  探索结构-活性关系（SAR）的新型构象约束顺式-3,6-二取代哌啶衍生物衍生自（2,2-二苯乙基）-[1-（4-氟苄基）哌啶-4-基甲基]胺（ I），通过衍生化铅的3位上的环外N原子，合成了一系列化合物。这项研究导致了取代苯基和杂环衍生物的形成。通过测量其竞争[3H] WIN 35 428，[3H]结合的能力，测试了所有新化合物在脑中对多巴胺转运蛋白（DAT），血清素转运蛋白（SERT）和去甲肾上腺素转运蛋白（NET）的亲和力。 ] citalopram和[3H] nisoxetine。还评估了所选化合物在抑制[3H] DA摄取方面的活性。SAR结果表明，苯环上取代的性质对于DAT的活性很重要，因为存在一个吸电子基团，该吸电子基团对效能的影响最大。杂环基团取代苄基中的苯环导致开发出对DAT具有中等活性的化合物。通过非对映异构体分离方法分离了两种最有效的外消旋化合物，并观察到对映异构体的亲和

  DOI：

  10.1021/jm020561w
• 作为产物：
  描述：

  N-(6-benzhydrylpiperidin-3-yl)-4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carboxamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以79%的产率得到cis-6-benzhydrylpiperidin-3-ylamine
  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-substituted 4-[2-( diphenylmethoxy) -ethyl]-1- (phenyl) methyl) piperidine analogs and methods of treating cns disorders therewith
  申请人：——

  公开号：US20030225133A1

  公开（公告）日：2003-12-04

  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. 1 2

  N-和O-取代的4-[2-二芳基甲氧基和甲氨基)烷基]哌啶具有高中枢神经系统活性，与多巴胺转运蛋白（DAT）和5-羟色胺转运蛋白（SERT）相关。优选化合物在DAT和SERT之间以及DAT和去甲肾上腺素转运蛋白（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用途，包括但不限于可卡因成瘾、抑郁症和帕金森病。
• N-and O-substituted 4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith
  申请人：Dutta K. Aloke

  公开号：US20050154021A1

  公开（公告）日：2005-07-14

  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]哌啶具有高中枢神经系统活性，与多巴胺转运体（DAT）和血清素转运体（SERT）有关。首选化合物在DAT和SERT之间以及在DAT和去甲肾上腺素转运体（NET）之间表现出高度差异的行为。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。
• 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。
• N- and O-Substituted 4-[2-(Diphenylmethoxy)-Ethyl]-1-[(Phenyl)Methyl]Piperdine Analogs and Methods of Treating CNS Disorders Therewith
  申请人：Dutta Aloke K.

  公开号：US20100016600A1

  公开（公告）日：2010-01-21

  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]哌啶具有高中枢神经系统活性，与多巴胺转运体（DAT）和血清素转运体（SERT）有关。优选化合物在DAT和SERT之间以及在DAT和去甲肾上腺素转运体（NET）之间表现出高度差异的行为。这些化合物在治疗中枢神经系统疾病，包括但不限于可卡因成瘾、抑郁症和帕金森病方面具有用途。
• N- and O-substituted 4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith
  申请人：Wayne State University

  公开号：US08211916B2

  公开（公告）日：2012-07-03

  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]哌啶具有相对于多巴胺转运体（DAT）和5-羟色胺转运体（SERT）的高中枢神经系统活性。优选化合物在DAT和SERT之间以及在DAT和去甲肾上腺素转运体（NET）之间表现出高度差异的行为。这些化合物在治疗中枢神经系统疾病方面具有用途，包括但不限于可卡因成瘾，抑郁症和帕金森病。