2-[3-[propyl(1,2,3,4-tetrahydro-5-methoxy-2-naphthalenyl)amino]propyl]-1H-isoindole-1,3(2H)-dione | 134796-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[3-[propyl(1,2,3,4-tetrahydro-5-methoxy-2-naphthalenyl)amino]propyl]-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[3-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-propylamino]propyl]isoindole-1,3-dione
• CAS: 134796-59-1
• 化学式: C₂₅H₃₀N₂O₃
• 分子量: 406.525
• InChiKey: XXRDESAFARMQAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-[propyl(1,2,3,4-tetrahydro-5-methoxy-2-naphthalenyl)amino]propyl]-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 1.0h， 生成 5-methoxy-2-[N-(3-aminopropyl)-N-n-propylamino]tetralin oxalate
  参考文献：
  名称：

  Structural analogues of 5-OMe-BPAT: synthesis and interactions with dopamine D2, D3, and serotonin 5-HT1A receptors

  摘要：

  Several structural analogues of 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1), a representative of a series of 2-aminotetralin-derived benzamides with po ten tial atypical antipsychotic properties, were synthesized and evaluated for their ability to bind to dopamine D-2A, D-3, and serotonin 5-HT1A receptors in vitro. The structure-affinity relationships revealed that the aromatic ring of the benzamide moiety of 1 contributes to the high affinities for all three receptor subtypes. Furthermore, 1 may interact with the dopamine D-2 and D-3 receptors through hydrogen bond formation with its carbonyl group. Investigation of the role of the amide hydrogen atom by amide N-alkylation was not conclusive, since conformational aspects may be responsible for the decreased dopaminergic affinities of the N'-alkylated analogues of 1. The effects of the amide modifications on the serotonin 5-HT1A receptor affinity were less pronounced, suggesting that the benzamidoethyl side-chain of 1 as a whole enhances the affinity for this receptor subtype probably through hydrophobic interactions with an accessory binding site. The structural requirements for the substituents at the basic nitrogen atom supported the hypothesis that the 2-aminotetralin moieties of the 2-aminotetralin-derived substituted benzamides may share the same binding sites as the 2-(N, N-di-n-propylamino)tetralins. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00039-5
• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 、 5-甲氧基-n-丙基-2-氨基四氢化萘盐酸盐 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以74%的产率得到2-[3-[propyl(1,2,3,4-tetrahydro-5-methoxy-2-naphthalenyl)amino]propyl]-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Structural analogues of 5-OMe-BPAT: synthesis and interactions with dopamine D2, D3, and serotonin 5-HT1A receptors

  摘要：

  Several structural analogues of 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1), a representative of a series of 2-aminotetralin-derived benzamides with po ten tial atypical antipsychotic properties, were synthesized and evaluated for their ability to bind to dopamine D-2A, D-3, and serotonin 5-HT1A receptors in vitro. The structure-affinity relationships revealed that the aromatic ring of the benzamide moiety of 1 contributes to the high affinities for all three receptor subtypes. Furthermore, 1 may interact with the dopamine D-2 and D-3 receptors through hydrogen bond formation with its carbonyl group. Investigation of the role of the amide hydrogen atom by amide N-alkylation was not conclusive, since conformational aspects may be responsible for the decreased dopaminergic affinities of the N'-alkylated analogues of 1. The effects of the amide modifications on the serotonin 5-HT1A receptor affinity were less pronounced, suggesting that the benzamidoethyl side-chain of 1 as a whole enhances the affinity for this receptor subtype probably through hydrophobic interactions with an accessory binding site. The structural requirements for the substituents at the basic nitrogen atom supported the hypothesis that the 2-aminotetralin moieties of the 2-aminotetralin-derived substituted benzamides may share the same binding sites as the 2-(N, N-di-n-propylamino)tetralins. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00039-5

文献信息

• Substituted 2-aminotetralins useful as dopaminergics
  申请人：Whitby Research, Inc.

  公开号：US05118704A1

  公开（公告）日：1992-06-02

  Optically active or racemic compounds are provided having the formula ##STR1## where R.sub.2, R.sub.3, R.sub.4 and R.sub.6 are defined in the specification; R.sub.1 is selected from the group consisting of ##STR2## wherein Y is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido, halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12, preferably 1 to 6, carbon atoms, and a is an integer of from zero to 3, for instance zero to 2; and pharmaceutically acceptable salts thereof; as dopaminergics.

  提供具有以下公式的光学活性或外消旋化合物：##STR1##其中，R.sub.2，R.sub.3，R.sub.4和R.sub.6在规范中有定义；R.sub.1从以下群体中选择：##STR2##其中，Y从羟基，硝基，氰基，偶氮基，氨基，酰胺基，羧酸胺基，三氟甲基，硫酸盐，磺酰胺基，卤素，碳氢基和杂原子取代的碳氢基基团中选择，其中所述杂原子从卤素，氮，氧，硫和磷的群体中选择，所述碳氢基基团包含1到12个，优选1到6个碳原子，a是从零到3的整数，例如零到2；以及其药学上可接受的盐作为多巴胺能药物。
• US5118704A
  申请人：——

  公开号：US5118704A

  公开（公告）日：1992-06-02
• Structural analogues of 5-OMe-BPAT: synthesis and interactions with dopamine D2, D3, and serotonin 5-HT1A receptors
  作者：Evert J. Homan、Esther Kroodsma、Swier Copinga、Lena Unelius、Nina Mohell、Håkan V. Wikström、Cor J. Grol

  DOI：10.1016/s0968-0896(99)00039-5

  日期：1999.6

  Several structural analogues of 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1), a representative of a series of 2-aminotetralin-derived benzamides with po ten tial atypical antipsychotic properties, were synthesized and evaluated for their ability to bind to dopamine D-2A, D-3, and serotonin 5-HT1A receptors in vitro. The structure-affinity relationships revealed that the aromatic ring of the benzamide moiety of 1 contributes to the high affinities for all three receptor subtypes. Furthermore, 1 may interact with the dopamine D-2 and D-3 receptors through hydrogen bond formation with its carbonyl group. Investigation of the role of the amide hydrogen atom by amide N-alkylation was not conclusive, since conformational aspects may be responsible for the decreased dopaminergic affinities of the N'-alkylated analogues of 1. The effects of the amide modifications on the serotonin 5-HT1A receptor affinity were less pronounced, suggesting that the benzamidoethyl side-chain of 1 as a whole enhances the affinity for this receptor subtype probably through hydrophobic interactions with an accessory binding site. The structural requirements for the substituents at the basic nitrogen atom supported the hypothesis that the 2-aminotetralin moieties of the 2-aminotetralin-derived substituted benzamides may share the same binding sites as the 2-(N, N-di-n-propylamino)tetralins. (C) 1999 Elsevier Science Ltd. All rights reserved.