[6-[2-Benzamidoethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl] trifluoromethanesulfonate | 257294-06-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: [6-[2-Benzamidoethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl] trifluoromethanesulfonate
• CAS: 257294-06-7
• 化学式: C₂₃H₂₇F₃N₂O₄S
• 分子量: 484.54
• InChiKey: YQYOJCXPUCXRJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [6-[2-Benzamidoethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl] trifluoromethanesulfonate 在 palladium diacetate 1,3-双(二苯基膦)丙烷 、 sodium methylate 、 formamide 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  C5-Substituted Derivatives of 5-OMe-BPAT: Synthesis and Interactions with Dopamine D2 and Serotonin 5-HT1A Receptors

  摘要：

  Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [H-3]-spiperone binding to rat striatal membranes containing dopamine D-2 receptors, and their ability to compete for [H-3]-8-OH-DPAT. binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D-2 receptors, with K-i-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1 as revealed by the higher K-i-values of 1-11. which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D-2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q(2) = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar CS-substituent should be optimal for a high affinity at this receptor subtype. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00196-0
• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 N-{2-[(5-Hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-ethyl}-benzamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到[6-[2-Benzamidoethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl] trifluoromethanesulfonate
  参考文献：
  名称：

  C5-Substituted Derivatives of 5-OMe-BPAT: Synthesis and Interactions with Dopamine D2 and Serotonin 5-HT1A Receptors

  摘要：

  Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [H-3]-spiperone binding to rat striatal membranes containing dopamine D-2 receptors, and their ability to compete for [H-3]-8-OH-DPAT. binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D-2 receptors, with K-i-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1 as revealed by the higher K-i-values of 1-11. which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D-2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q(2) = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar CS-substituent should be optimal for a high affinity at this receptor subtype. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00196-0

文献信息

• C5-Substituted Derivatives of 5-OMe-BPAT: Synthesis and Interactions with Dopamine D2 and Serotonin 5-HT1A Receptors
  作者：Evert J. Homan、Martin Th.M. Tulp、Jonas E. Nilsson、Håkan V. Wikström、Cor J. Grol

  DOI：10.1016/s0968-0896(99)00196-0

  日期：1999.11

  Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [H-3]-spiperone binding to rat striatal membranes containing dopamine D-2 receptors, and their ability to compete for [H-3]-8-OH-DPAT. binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D-2 receptors, with K-i-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1 as revealed by the higher K-i-values of 1-11. which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D-2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q(2) = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar CS-substituent should be optimal for a high affinity at this receptor subtype. (C) 1999 Elsevier Science Ltd. All rights reserved.