罗替戈汀中间体 | 93601-85-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 罗替戈汀中间体
• 中文别名: (R)-1,2,3,4-四氢-5-甲氧基-N-丙基-2-萘胺盐酸盐
• 英文名称: (2R)-5-methoxy-2-propylaminotetralin hydrochloride
• 英文别名: (R)-5-methoxy-2-(N-n-propylamino)tetralin hydrochloride；(R)-2-(N-propylamino)-5-methoxytetralin hydrochloride；(R)-(+)-(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propylamine hydrochloride；(R)-1,2,3,4-Tetrahydro-5-methoxy-N-propyl-2-naphthalenamine Hydrochloride；(2R)-5-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride
• CAS: 93601-85-5
• 化学式: C₁₄H₂₁NO*ClH
• 分子量: 255.788
• InChiKey: ZOKTXMBBTXQAIC-UTONKHPSSA-N

物化性质

• 溶解度：
  氯仿（微溶）、甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  罗替戈汀中间体 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 三溴化硼 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (6R)-6-(二丙基氨基)-5,6,7,8-四氢-1-萘酚
  参考文献：
  名称：

  解析的单酚2-氨基四氢萘草酸和1,2,3,4,4a，5,6,10b-八氢苯并[f]喹啉：集中作用于突触前和突触后多巴胺受体激动剂的结构和立体化学考虑。

  摘要：

  揭示了作用在突触前和突触后DA受体上的中枢作用多巴胺（DA）激动剂的详细结构-活性关系。解析出的化合物为5-和7-羟基-2-（二-正丙基氨基）四氢萘林和顺-和反7-羟基-4-正丙基-1,2,3,4,4a，5,6 ，10b-八氢苯并[f]喹啉。通过将这些化合物的更具活性的对映异构体的结构与已知的多巴胺能激动剂，阿扑吗啡和麦角灵重叠，可以提出一种新的DA受体模型，作为当前DA受体理论的产物。该受体模型最重要的概念之一是强调多巴胺能化合物的N取代基可能占据的位置。这些位置中的一个在空间上定义得很好，而另一个方向在空间上不太重要。该模型已被用来解释某些先前报道的结构缺乏多巴胺能活性，还用于预测新型结构的特性，包括固有手性，该结构应对DA受体具有活性。希望这种启发式DA受体模型将导致发现更多选择性和有效药理学工具，最终可能导致开发用于治疗中枢神经系统多巴胺能功能疾病的治疗剂。

  DOI：

  10.1021/jm00380a012
• 作为产物：
  描述：

  在 水 、 sodium hydroxide 、 盐酸 作用下， 反应 2.0h， 生成 罗替戈汀中间体
  参考文献：
  名称：

  Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol

  摘要：

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-{[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.025

文献信息

• Synthesis, resolution and radioiodination of S(−)trans-5-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)amino]tetralin-S(−)trans-5-OH-PIPAT: A new dopamine D2-like receptor ligand
  作者：Sumalee Chumpradit、Mei-Ping Kung、Janet Vessotskie、Hank F. Kung

  DOI：10.1002/jlcr.2580361105

  日期：1995.11

  A new dopamine D2-like receptor ligand, (R,S)trans-5-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin ((R,S)trans-5-OH-PIPAT, 3), based on high affinity dopamine receptor agonist 5-hydroxy-2-[N,N-(di-n-propyl)-2-amino]tetralin (5-OH-DPAT, 1), was prepared. The synthesis was achieved by a reductive animation of 5-methoxy-2-tetralone with n-propylamine, followed by N-alkylation, to afford

  一种新的多巴胺 D2 样受体配体，(R,S)trans-5-hydroxy-2-[Nn-丙基-N-(3'-iodo-2'-propenyl)amino]tetralin ((R,S)trans -5-OH-PIPAT, 3)，基于高亲和力多巴胺受体激动剂 5-羟基-2-[N,N-(二正丙基)-2-氨基]萘满 (5-OH-DPAT, 1) ，准备好了。该合成是通过 5-甲氧基-2-四氢萘酮与正丙胺的还原胺化，然后进行 N-烷基化，得到 5-甲氧基-N-丙基-N-2'-丙炔基-2-氨基四氢萘，7。用三丁基氢化锡还原 7 得到三正丁基锡衍生物 8，通过碘脱金属反应将其转化为 9。9 的去甲基化得到所需的化合物，(R,S)trans-5-OH-PIPAT, 3。解析的 (R) 和 (S)trans-5-OH-PIPAT, 3 也被定量制备。体外结合研究表明，这种新化合物具有立体选择性，可与多巴胺 D2
• Persson, Marie; Hacksell, Uli; Csoeregh, Ingeborg, Journal of the Chemical Society. Perkin transactions I, 1991, # 6, p. 1453 - 1459
  作者：Persson, Marie、Hacksell, Uli、Csoeregh, Ingeborg

  DOI：——

  日期：——
• Resolved monophenolic 2-aminotetralins and 1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines: structural and stereochemical considerations for centrally acting pre- and postsynaptic dopamine-receptor agonists
  作者：Haakan Wikstroem、Bengt Andersson、Domingo Sanchez、Per Lindberg、Lars Erik Arvidsson、Anette M. Johansson、J. Lars G. Nilsson、Kjell Svensson、Stephan Hjorth、Arvid Carlsson

  DOI：10.1021/jm00380a012

  日期：1985.2

  centrally acting dopamine (DA) agonists acting on both pre- and postsynaptic DA receptors. The compounds resolved are 5- and 7-hydroxy-2-(di-n-propylamino)tetralin and cis- and trans-7-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo [f]quinoline. By the superimposition of the structures of the more active enantiomers of these compounds with those of known dopaminergic agonists, apomorphine and ergolines

  揭示了作用在突触前和突触后DA受体上的中枢作用多巴胺（DA）激动剂的详细结构-活性关系。解析出的化合物为5-和7-羟基-2-（二-正丙基氨基）四氢萘林和顺-和反7-羟基-4-正丙基-1,2,3,4,4a，5,6 ，10b-八氢苯并[f]喹啉。通过将这些化合物的更具活性的对映异构体的结构与已知的多巴胺能激动剂，阿扑吗啡和麦角灵重叠，可以提出一种新的DA受体模型，作为当前DA受体理论的产物。该受体模型最重要的概念之一是强调多巴胺能化合物的N取代基可能占据的位置。这些位置中的一个在空间上定义得很好，而另一个方向在空间上不太重要。该模型已被用来解释某些先前报道的结构缺乏多巴胺能活性，还用于预测新型结构的特性，包括固有手性，该结构应对DA受体具有活性。希望这种启发式DA受体模型将导致发现更多选择性和有效药理学工具，最终可能导致开发用于治疗中枢神经系统多巴胺能功能疾病的治疗剂。
• Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol
  作者：Balaram Ghosh、Tamara Antonio、Bhaskar Gopishetty、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2010.06.025

  日期：2010.8

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.