1'-benzyl-1,2,3,4-tetrahydrospiro[naphthalene-2,4'-piperidin]-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1'-benzyl-1,2,3,4-tetrahydrospiro[naphthalene-2,4'-piperidin]-1-one
• 英文别名: 1'-Benzylspiro[3,4-dihydronaphthalene-2,4'-piperidine]-1-one
• 化学式: C₂₁H₂₃NO
• 分子量: 305.42
• InChiKey: PZWPPSAANHYITK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1'-benzyl-1,2,3,4-tetrahydrospiro[naphthalene-2,4'-piperidin]-1-one 在 dimethyl sulfide borane 作用下， 以 二乙二醇二甲醚 为溶剂， 以76%的产率得到1'-benzyl-3,4-dihydro-1H-spiro[naphthalene-2,4'-piperidine]
  参考文献：
  名称：

  新颖高度有效的和选择性σ 1受体拮抗剂相关的Spipethiane

  摘要：

  引线spipethiane的核心结构的保守性的化学修饰（1），得到新的有效σ 1个配体。σ 1亲和力和σ 1 / σ 2选择性证明通过在位置3或4（引入极性官能团（氧原子或羰基）受到青睐4 - 6）或通过的距离的两个疏水性部分之间的伸长在位置4（8和9）上同时存在羰基的分子。针对人乳腺癌细胞系MCF-7所观察到的细胞抑制效应/ ADR，高度表达σ 1受体，而不是针对MCF-7，以及吗啡镇痛的增强强调σ 1这一系列化合物的拮抗剂轮廓。特别是，由于其高σ 1和亲和力（P ķ我= 10.28）和σ 1 /σ 2选择性比率（29510），化合物9可能是σ受体表征新颖有价值的工具和用于合理设计一个合适的模板潜在治疗上有用的σ 1拮抗剂。

  DOI：

  10.1021/jm901542q
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 sodium hydroxide 、 甲烷磺酸 、 phosphorus pentoxide 、 三乙胺 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 80.5h， 生成 1'-benzyl-1,2,3,4-tetrahydrospiro[naphthalene-2,4'-piperidin]-1-one
  参考文献：
  名称：

  Piperidinyltetralin .sigma. Ligands

  摘要：

  sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT(2) receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT(2) receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).

  DOI：

  10.1021/jm00029a008

文献信息

• Tricyclic analgesics
  申请人：——

  公开号：US20040266802A1

  公开（公告）日：2004-12-30

  A tricyclic compound of Formula (I): wherein: R 1 is hydrogen or hydroxy; R 2 is hydrogen or hydroxy; or R 1 and R 2 together are oxygen; A is a bond, CH 2 , CH CH 3 , CH 2 CH 2 or C(CH 3 ) 2 ; R 3 and R 4 are the same or different and are hydrogen, halo, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, trifluoromethyl NO 2 , COR 6 , COOR 6 or NR 6 R 7 , wherein R 6 and R 7 are the same or different and are hydrogen, C 1 -C 6 alkyl or benzyl; R 5 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, (O═C)—C 1-6 alkyl, (O═C)—C 2-6 alkenyl, (O═C)—C 3-6 cycloalkyl wherein said alkyl, alkenyl and cycloalkyl groups can be substituted by 1, 2 or 3 groups selected from halo, C 3 -C 6 cycloalkyl, phenyl or substituted phenyl, and salts thereof, are particularly useful for treating, among other indications, neuropathic pain and other CNS disorders. 1

  公式（I）的三环化合物：其中：R 1 为氢或羟基；R 2 为氢或羟基；或R 1 和R 2 一起为氧；A为键，CH 2 ，CH CH 3 ，CH 2 CH 2 或C(CH 3 ) 2 ；R 3 和R 4 相同或不同，为氢，卤素，C 1 -C 6 烷基，C 1 -C 4 烷氧基，三氟甲基NO 2 ，COR 6 ，COOR 6 或NR 6 R 7 ，其中R 6 和R 7 相同或不同，为氢，C 1 -C 6 烷基或苄基；R 5 为氢，C 1-6 烷基，C 2-6 烯基，C 3-6 环烷基，（O═C）—C 1-6 烷基，（O═C）—C 2-6 烯基，（O═C）—C 3-6 环烷基，其中所述烷基，烯基和环烷基基团可被1、2或3个来自卤素，C 3 -C 6 环烷基，苯基或取代苯基的基团取代，以及其盐，特别适用于治疗神经病性疼痛和其他中枢神经系统疾病等适应症。
• TRICYCLIC ANALGESICS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1235808A2

  公开（公告）日：2002-09-04
• [EN] TRICYCLIC ANALGESICS<br/>[FR] ANALGESIQUES TRICYCLIQUES
  申请人：WARNER LAMBERT CO

  公开号：WO2000075116A2

  公开（公告）日：2000-12-14

  A tricyclic compound of Formula (I): wherein: R1 is hydrogen or hydroxy; R2 is hydrogen or hydroxy; or R?1 and R2¿ together are oxygen; A is a bond, CH¿2?, CH CH3, CH2 CH2 or C(CH3)2; R?3 and R4¿ are the same or different and are hydrogen, halo, C¿1?-C6 alkyl, C1-C4 alkoxy, trifluoromethyl, NO2, COR?6, COOR6 or NR6R7¿, wherein R?6 and R7¿ are the same or different and are hydrogen, C¿1?-C6 alkyl or benzyl; R?5¿ is hydrogen, C¿1-6? alkyl, C2-6 alkenyl, C3-6 cycloalkyl, (O=C)-C1-6 alkyl, (O=C)-C2-6 alkenyl, (O=C)-C3-6 cycloalkyl, wherein said alkyl, alkenyl and cycloalkyl groups can be substituted by 1, 2 or 3 groups selected from halo, C3-C6 cycloalkyl, phenyl or substituted phenyl, and salts thereof, are particularly useful for treating, among other indications, neuropathic pain and other CNS disorders.
• Piperidinyltetralin .sigma. Ligands
  作者：Paul J. Gilligan、Ahmed A. Kergaye、Bryan M. Lewis、John F. McElroy

  DOI：10.1021/jm00029a008

  日期：1994.2

  sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT(2) receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT(2) receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).
• Novel Highly Potent and Selective σ₁ Receptor Antagonists Related to Spipethiane
  作者：Alessandro Piergentili、Consuelo Amantini、Fabio Del Bello、Mario Giannella、Laura Mattioli、Maura Palmery、Marina Perfumi、Maria Pigini、Giorgio Santoni、Paolo Tucci、Margherita Zotti、Wilma Quaglia

  DOI：10.1021/jm901542q

  日期：2010.2.11

  Conservative chemical modifications of the core structure of the lead spipethiane (1) afforded novel potent σ1 ligands. σ1 affinity and σ1/σ2 selectivity proved to be favored by the introduction of polar functions (oxygen atom or carbonyl group) in position 3 or 4 (4−6) or by the elongation of the distance between the two hydrophobic portions of the molecule with the simultaneous presence of a carbonyl

  引线spipethiane的核心结构的保守性的化学修饰（1），得到新的有效σ 1个配体。σ 1亲和力和σ 1 / σ 2选择性证明通过在位置3或4（引入极性官能团（氧原子或羰基）受到青睐4 - 6）或通过的距离的两个疏水性部分之间的伸长在位置4（8和9）上同时存在羰基的分子。针对人乳腺癌细胞系MCF-7所观察到的细胞抑制效应/ ADR，高度表达σ 1受体，而不是针对MCF-7，以及吗啡镇痛的增强强调σ 1这一系列化合物的拮抗剂轮廓。特别是，由于其高σ 1和亲和力（P ķ我= 10.28）和σ 1 /σ 2选择性比率（29510），化合物9可能是σ受体表征新颖有价值的工具和用于合理设计一个合适的模板潜在治疗上有用的σ 1拮抗剂。