1''-[4-(4-fluorophenyl)-4-oxobutyl]-3,4-dihydro-1H-spiro[naphthalene-2,4''-piperidine]-1-one chloride | 152830-66-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1''-[4-(4-fluorophenyl)-4-oxobutyl]-3,4-dihydro-1H-spiro[naphthalene-2,4''-piperidine]-1-one chloride
• 英文别名: 1'-(2-phenylethyl)spiro[3,4-dihydronaphthalene-2,4'-piperidine]-1-one
• CAS: 152830-66-5
• 化学式: C₂₂H₂₅NO
• 分子量: 319.447
• InChiKey: RGHKOAFUHZEYJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 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''-[4-(4-fluorophenyl)-4-oxobutyl]-3,4-dihydro-1H-spiro[naphthalene-2,4''-piperidine]-1-one chloride 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 14.0h， 以83%的产率得到3,4-dihydro-1-hydroxynaphthalene-2(1H)-spiro-4'-<1-(2-phenylethyl)piperidine>
  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
• 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''-[4-(4-fluorophenyl)-4-oxobutyl]-3,4-dihydro-1H-spiro[naphthalene-2,4''-piperidine]-1-one chloride
  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。
• Gilligan Paul J., Kergaye Ahmed A., Lewis Bryan M., McElroy John F., J. Med. Chem, 37 (1994) N 3, S 364-370
  作者：Gilligan Paul J., Kergaye Ahmed A., Lewis Bryan M., McElroy John F.

  DOI：——

  日期：——
• 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).