(+)-(R)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl methanesulfonate | 152148-49-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+)-(R)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl methanesulfonate
• 英文别名: [(1R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl]methyl methanesulfonate
• CAS: 152148-49-7
• 化学式: C₁₃H₁₈O₄S
• 分子量: 270.35
• InChiKey: HMSGHDKBRDQTSF-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-(R)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl methanesulfonate 在 氯化亚砜 、 硫酸 、 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 11.0h， 生成 1-Diazo-3-((S)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-propan-2-one
  参考文献：
  名称：

  1-Aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)alkyl]piperazines and Their Analogues:  Influence of the Stereochemistry of the Tetrahydronaphthalen-1-yl Nucleus on 5-HT_1A Receptor Affinity and Selectivity versus α₁ and D₂ Receptors. 5

  摘要：

  Some 1-aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was det;ermined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D-2, and alpha(1) receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D-2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha(1) receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (greater than or equal to 250-fold) versus both D-2 and alpha(1) receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [S-35]GTP gamma S binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor.

  DOI：

  10.1021/jm980420n
• 作为产物：
  描述：

  5-甲氧基-3,4-二氢-2H-1-萘酮 在 氢氧化钾 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 草酰氯 、 二甲基十二/十四烷基叔胺 、 锂丁酯 、 对甲苯磺酸 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙二醇 、 苯 为溶剂， 反应 31.75h， 生成 (+)-(R)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl methanesulfonate
  参考文献：
  名称：

  Structure−Activity Studies for a Novel Series of N-(Arylethyl)-N-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamines Possessing Dual 5-HT Uptake Inhibiting and α₂-Antagonistic Activities

  摘要：

  In search of an alpha(2)-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha(2)-receptor (K-i = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha(2)-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-l are optimal with alternate substitutions producing compounds retaining high affinity for the alpha(2)-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the g-position of the tetralin.

  DOI：

  10.1021/jm960723m

文献信息

• [EN] TRITIUM RADIOLABELING OF [3H]-1-CYCLOHEXYL-4-[3-(5-METHOXY-1,2, 3,4,-TETRAHYDRONAPHTHALEN-1-YL)-N-PROPYL]PIPERAZINE ([3H]-PB28), AS A POTENT SIGMA-2 RECEPTOR LIGAND<br/>[FR] RADIOMARQUAGE AU TRITIUM DE [3H]-1-CYCLOHEXYL-4-[3-(5- MÉTHOXY-1,2,3,4-TÉTRAHYDRONAPHTALÈN-1-YL)-N-PROPYL]PIPÉRAZINE ([3H]-PB28), EN TANT QUE LIGAND EFFICACE DES RÉCEPTEURS SIGMA-2
  申请人：UNIV BARI

  公开号：WO2009104058A1

  公开（公告）日：2009-08-27

  The invention relates to a novel process for the radiolabeling with [3H] of the l-cyclohexyl-4- [3- (5- methoxy-1, 2,3,4, -tetrahydronaphthalen-1-yl) -n- propyl]piperazine (PB28) ligand of formula 1 and enantiomeric forms thereof, specific for the sigma-2 receptors. The invention further relates to the same radiolabeled ligand and to its use as a highly selective analytical instrument in the evaluation of the expression levels of said receptors in tissues, as selection tool of novel specific ligands, and as diagnostic agent in diagnostic kits.

  该发明涉及一种新型方法，用于对公式1中的l-环己基-4-[3-(5-甲氧基-1,2,3,4,-四氢萘基)-n-丙基]哌嗪（PB28）配体进行[3H]放射标记，以及其对映体形式，特异于sigma-2受体。该发明还涉及同一放射标记的配体及其用途，作为在组织中评估所述受体表达水平的高度选择性分析仪器，作为新型特异性配体的选择工具，并作为诊断试剂盒中的诊断试剂。
• Analogues of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) with Added Polar Functionality and Reduced Lipophilicity for Potential Use as Positron Emission Tomography Radiotracers
  作者：Carmen Abate、Mauro Niso、Enza Lacivita、Philip D. Mosier、Annamaria Toscano、Roberto Perrone

  DOI：10.1021/jm1013133

  日期：2011.2.24

  1-Cyclohexyl-4[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) represents an excellent lead candidate for therapeutic and/or diagnostic applications in oncology. However, because its utility is limited by its relatively high degree of lipophilicity, novel analogues of 1 with reduced lipophilic character were designed by substituting methylene groups with more polar functional groups in the propylene linker and at the tetralin C4 position. For the chiral analogues, separate enantiomers exhibited substantial and roughly equal affinities within a given receptor subtype, with the greatest difference observed for compound 9 at sigma(1) (7.5-fold; (-)-(S)-9 K(i) = 94.6 nM, (+)-(R)-9 K(i) = 12.6 nM). Compound (-)-(S)-9 was also found to be the most sigma(2)-selective agent (sigma(2) K(i) = 5.92 nM), to possess a lipophilicity consistent with entry into tumor cells (log D(7.4) = 2.38), and to show minimal antiproliferative activity. However, (-)-(S)-9 exhibited moderate activity (EC(50) = 8.1 mu M) at the P-gp efflux pump.
• Structure−Activity Studies for a Novel Series of <i>N</i>-(Arylethyl)-<i>N</i>-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-<i>N</i>-methylamines Possessing Dual 5-HT Uptake Inhibiting and α₂-Antagonistic Activities
  作者：Michael D. Meyer、Arthur A. Hancock、Karin Tietje、Kevin B. Sippy、Rajnandan Prasad、David M. Stout、David L. Arendsen、B. Greg Donner、William A. Carroll

  DOI：10.1021/jm960723m

  日期：1997.3.1

  In search of an alpha(2)-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha(2)-receptor (K-i = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha(2)-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-l are optimal with alternate substitutions producing compounds retaining high affinity for the alpha(2)-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the g-position of the tetralin.
• 1-Aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)alkyl]piperazines and Their Analogues:  Influence of the Stereochemistry of the Tetrahydronaphthalen-1-yl Nucleus on 5-HT_1A Receptor Affinity and Selectivity versus α₁ and D₂ Receptors. 5
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Vincenzo Tortorella

  DOI：10.1021/jm980420n

  日期：1999.2.1

  Some 1-aryl-4-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazines and their alkylamino and alkylamido analogues, previously studied as 5-HT1A ligands, were prepared in enantiomerically pure form, and their absolute configuration was det;ermined by chemical correlation or by chiroptical properties. They were evaluated for in vitro 5-HT1A, D-2, and alpha(1) receptor affinity by radioligand binding assays, to study the influence of the chiral carbon atom of the tetrahydronaphthalene nucleus on the 5-HT1A affinity and selectivity. Results indicated that, as regarding the 5-HT1A receptor affinity, there was no difference in affinity between (-)- and (+)-enantiomers as well as the racemate of each compound. The stereochemistry, instead, influenced the selectivity: all (-)-enantiomers displayed affinity values higher than those of (+)-isomers at D-2 receptors, and conversely, all (+)-enantiomers displayed affinity values higher than those of (-)-isomers at alpha(1) receptors. As a result of this trend, it is not possible to predict the isomer with a better selectivity profile. However, compounds (S)-(+)-2, (S)-(+)-4, and (R)-(+)-6 displayed high affinity for the 5-HT1A receptor (IC50 values ranging between 7.0 and 2.3 nM) and good selectivity (greater than or equal to 250-fold) versus both D-2 and alpha(1) receptors. Furthermore, compounds (S)-(+)-4 and (R)-(-)-4 were submitted to the [S-35]GTP gamma S binding assay for a preliminary evaluation of their intrinsic activity on the 5-HT1A receptor.