(R)-(+)-5-methoxy-1,2,3,4-tetrahydro-1-naphthalenemethanol | 152148-48-6

• 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-tetrahydro-1-naphthalenemethanol
• 英文别名: (R)-5-Methoxy-1,2,3,4-tetrahydronapthalene-1-methanol；[(1R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl]methanol
• CAS: 152148-48-6
• 化学式: C₁₂H₁₆O₂
• 分子量: 192.258
• InChiKey: XFDFCLXIMZGIBR-VIFPVBQESA-N

物化性质

• 沸点：
  330.9±35.0 °C(predicted)
• 密度：
  1.075±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-(+)-5-methoxy-1,2,3,4-tetrahydro-1-naphthalenemethanol 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 49.0h， 生成 1-[(1R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl]-N-methylmethanamine
  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
• 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 、 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 30.75h， 生成 (R)-(+)-5-methoxy-1,2,3,4-tetrahydro-1-naphthalenemethanol
  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

• Tertiary and secondary amines as alpha-2 antagonists and serotonin
  申请人：Abbott Laboratories

  公开号：US05288749A1

  公开（公告）日：1994-02-22

  The present invention provides tertiary and secondary amine compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof which are antagonists for alpha-2 adrenoreceptors and which inhibit serotonin (5-hydroxytryptamine, 5-HT) uptake.

  本发明提供了公式##STR1##的三级和二级胺化合物及其药用盐，这些化合物是α-2肾上腺素受体拮抗剂，可以抑制血清素（5-羟色胺，5-HT）的摄取。
• 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.
• TERTIARY AND SECONDARY AMINES AS ALPHA-2 ANTAGONISTS AND SEROTONIN UPTAKE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP0646112A1

  公开（公告）日：1995-04-05
• EP0646112A4
  申请人：——

  公开号：EP0646112A4

  公开（公告）日：1997-04-02
• US5288749A
  申请人：——

  公开号：US5288749A

  公开（公告）日：1994-02-22