(+)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol | 101470-24-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol
• 英文别名: (R)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol；(+)-(2R)-2-(n-propylamino)-5-hydroxytetralin；(6R)-5,6,7,8-Tetrahydro-6-(propylamino)-1-naphthalenol；(6R)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol
• CAS: 101470-24-0
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: VCYPZWCFSAHTQT-LLVKDONJSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol 在 盐酸 、 盐酸羟胺 、 N,N-二异丙基乙胺 、 potassium iodide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 19.0h， 生成 (S)-5-{4-[(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl) (propyl)-amino]butoxy} pyrazolo[1,5-a]pyridine-3-carbaldehyde oxime
  参考文献：
  名称：

  具有吡唑并[1,5- a ]吡啶亚结构的G蛋白偏多巴胺能药物的发现

  摘要：

  1,4-二取代的芳族哌嗪是由胺能G蛋白偶联受体识别的优先结构基序。通过适当的接头将亲脂性部分连接至芳基哌嗪核心代表了增加结合亲和力和微调功能特性的有前途的概念。特别地，吡唑并[1，5- a ]吡啶杂环附件的掺入导致一系列高亲和力的多巴胺受体部分激动剂。涉及BRET生物传感器，结合研究，电生理学和基于互补的测定的综合药理学表征表明，与多巴胺D 2处的β-arrestin募集相比，G蛋白质（优选G o）的活化更有利于化合物的活化。受体。对于代表性的2-甲氧基苯基哌嗪16c，证明了设计G蛋白偏向的局部激动剂作为推定的新疗法的可行性，该化合物明确地显示了体内的抗精神病活性。此外，吡唑并[1，5- a ]吡啶附肢与5-羟基-N-丙基-2-氨基四氢联苯胺单元的组合导致平衡或G蛋白偏倚的多巴胺能配体，这取决于头基的立体化学，说明了复杂多巴胺D 2受体的结构-功能选择性关系。

  DOI：

  10.1021/acs.jmedchem.6b01857
• 作为产物：
  描述：

  (2R)-1,2,3,4-四氢-5-甲氧基-N-丙基-2-萘胺 在 氢溴酸 作用下， 反应 16.0h， 生成 (+)-6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol
  参考文献：
  名称：

  具有吡唑并[1,5- a ]吡啶亚结构的G蛋白偏多巴胺能药物的发现

  摘要：

  1,4-二取代的芳族哌嗪是由胺能G蛋白偶联受体识别的优先结构基序。通过适当的接头将亲脂性部分连接至芳基哌嗪核心代表了增加结合亲和力和微调功能特性的有前途的概念。特别地，吡唑并[1，5- a ]吡啶杂环附件的掺入导致一系列高亲和力的多巴胺受体部分激动剂。涉及BRET生物传感器，结合研究，电生理学和基于互补的测定的综合药理学表征表明，与多巴胺D 2处的β-arrestin募集相比，G蛋白质（优选G o）的活化更有利于化合物的活化。受体。对于代表性的2-甲氧基苯基哌嗪16c，证明了设计G蛋白偏向的局部激动剂作为推定的新疗法的可行性，该化合物明确地显示了体内的抗精神病活性。此外，吡唑并[1，5- a ]吡啶附肢与5-羟基-N-丙基-2-氨基四氢联苯胺单元的组合导致平衡或G蛋白偏倚的多巴胺能配体，这取决于头基的立体化学，说明了复杂多巴胺D 2受体的结构-功能选择性关系。

  DOI：

  10.1021/acs.jmedchem.6b01857

文献信息

• Further Structure–Activity Relationships Study of Hybrid 7-{[2-(4-Phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol Analogues: Identification of a High-Affinity D3-Preferring Agonist with Potent in Vivo Activity with Long Duration of Action
  作者：Swati Biswas、Suhong Zhang、Fernando Fernandez、Balaram Ghosh、Juan Zhen、Eldo Kuzhikandathil、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm070860r

  日期：2008.1.1

  (+)-isomeric counterpart. Binding results indicated highest selectivity for D3 receptors in compound (-)- 10 ( K i = 0.35 nM; D2/D3 = 71). In the 5-hydroxy series, highest selectivity for D3 receptors was exhibited by compound (-)- 25 ( K i = 0.82 nM; D2/D3 = 31.5). Most potent compounds exhibited binding and functional affinities at the sub-nanomolar level for the D3 receptor. Binding assays were carried

  本文介绍了一种针对多巴胺D2 / D3受体的氨基四氢萘-哌嗪类杂合分子的扩展结构-活性关系研究。已经开发出各种类似的作为位置异构体的类似物，其中酚羟基在芳族环上的位置已经改变。在两个邻苯二酚衍生物之间，具有两个亚甲基接头长度的化合物6e相对于具有四个亚甲基接头的化合物6f对D3的表现出更高的亲和力和对D3的选择性（6e和6f分别为D2 / D3 = 50.6 vs 7.51）。通常，（-）-异构体比（+）-异构体更有效。结合结果表明对化合物（-）-10中的D3受体具有最高选择性（K i = 0.35 nM； D2 / D3 = 71）。在5-羟基系列中，化合物（-）-25（K i = 0.）对D3受体的选择性最高。82 nM；D2 / D3 = 31.5）。大多数有效的化合物在亚纳摩尔水平上对D3受体表现出结合和功能亲和力。用tri化的烯酮作为放​​射性配体，用表达D2或D3受体的HEK-
• Structure-activity relationships of dopaminergic 5-hydroxy-2-aminotetralin derivatives with functionalized N-alkyl substituents
  作者：Max P. Seiler、Andre P. Stoll、Annemarie Closse、Willy Frick、Annelise Jaton、Jean Marie Vigouret

  DOI：10.1021/jm00156a007

  日期：1986.6

  5-Hydroxy-2-aminotetralin derivatives in which one N-alkyl substituent carries a functional group have been prepared and their dopaminergic activities compared with those of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) and known ergolines. Several members of the series demonstrated high affinities in dopamine (DA) receptor binding and DA agonist properties in the rotational behavior model in the range of known potent ergolines. The results suggest that the accessory binding site for the larger N-alkyl substituent of the 5-hydroxy-2-aminotetralins can accommodate various neutral and bulky functionalities and is probably identical with the site(s) to which the 8-substituents of the ergolines bind.
• Molecular Determinants of Biased Agonism at the Dopamine D₂Receptor
  作者：Dietmar Weichert、Ashutosh Banerjee、Christine Hiller、Ralf C. Kling、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm501889t

  日期：2015.3.26

  The development of biased (functionally selective) ligands Provides a formidable challenge in medicinal chemistry. In an effort to learn to design functionally selective molecular tools for the highly therapeutically relevant dopamine D-2 receptor, we synthesized a collection of agonists based on structurally distinct head groups derived from canonical or atypical dopaminergic pharmacophores. The test compounds feature a long lipophilic appendage that was shown to mediate biased signaling. By employing functional assays and molecular dynamics simulations, we could show that atypical dopamine surrogates of type 1 and 2 promote biased signaling, while ligands built from classical dopaminergic head groups (type 3 and 4) typically elicit more balanced signaling profiles. Besides this, we found a strong influence of the stereochemistry of type 4 aminotetraline-derived agonists on functional selectivity at D-2 receptors. Whereas the (S)-enantiomer behaved as a full agonist, the biased ligand (R)-4 induced poor G protein coupling but substantial beta-arrestin recruitment.
• Methods of treating a subject using bioreversible derivatives of hydroxy n-substituted-2-aminotetralins
  申请人：Spriaso LLC

  公开号：US20160016887A1

  公开（公告）日：2016-01-21

  Described are compositions that may be orally administered that comprise a bioreversible derivative of hydroxy N-substituted-2-aminotetralin or an enantiomer or salt or prodrug thereof, and a pharmaceutically acceptable carrier suitable for oral administration in the amount present, wherein the composition is orally bioavailable when administered to a subject. The bioreversible derivative has an intrinsic lipophilicity C log P value of about 7 to about 11.5. A method comprises oral administering such composition to a human subject in need of hydroxy N-substituted-2-aminotetralin therapy.
• COMPOSITIONS COMPRISING BIOREVERSIBLE DERIVATIVES OF HYDROXY N- SUBSTITUTED-2-AMINOTETRALINS, DOSAGE FORMS, AND RELATED METHODS
  申请人：Spriaso LLC

  公开号：US20160015684A1

  公开（公告）日：2016-01-21

  Described are compositions that may be orally administered that comprise a bioreversible derivative of hydroxy N-substituted-2-aminotetralin or an enantiomer or salt or prodrug thereof, and a pharmaceutically acceptable carrier suitable for oral administration in the amount present, wherein the composition is orally bioavailable when administered to a subject. The bioreversible derivative has an intrinsic lipophilicity C log P value of about 7 to about 11.5. A method comprises oral administering such composition to a human subject in need of hydroxy N-substituted-2-aminotetralin therapy.