1-(3-dimethylaminopropyl)-1-naphthalen-1-yl-1,3-dihydroisobenzofuran-5-carbonitrile | 1448549-66-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(3-dimethylaminopropyl)-1-naphthalen-1-yl-1,3-dihydroisobenzofuran-5-carbonitrile
• 英文别名: 1-[3-(dimethylamino)propyl]-1-naphthalen-1-yl-3H-2-benzofuran-5-carbonitrile
• CAS: 1448549-66-3
• 化学式: C₂₄H₂₄N₂O
• 分子量: 356.467
• InChiKey: AAWULYVNLMFIDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  magnesium,N,N-dimethylpropan-1-amine,chloride 、 5-氰基苯酞 、 1-萘基溴化镁, 0.5M IN METHF 在 三乙胺 、 对甲苯磺酰氯 作用下， 生成 1-(3-dimethylaminopropyl)-1-naphthalen-1-yl-1,3-dihydroisobenzofuran-5-carbonitrile
  参考文献：
  名称：

  X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT

  摘要：

  The recent publication of X-ray structures of SERT includes structures with the potent antidepressant S-Citalopram (S-Cit). Earlier predictions of ligand binding at both a primary (S1) and an allosteric modulator site (S2), were confirmed. We provide herein examples of a series of Citalopram analogs, showing distinct structure-activity relationship (SAR) at both sites that is independent of the SAR at the other site. Analogs with a higher affinity and selectivity than benchmark R-Citalopram (R-Cit) for the S2 versus the S1 site were identified. We deploy structural and computational analyses to explain this SAR and demonstrate the potential utility of the newly emerging X-ray structures within the neurotransmitter:sodium Symporter family for drug design. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.12.037

文献信息

• [EN] SELECTIVE ALLOSTERIC MODULATORS OF THE SEROTONIN TRANSPORTER<br/>[FR] MODULATEURS ALLOSTÉRIQUES SÉLECTIFS DU TRANSPORTEUR DE LA SÉROTONINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2013110313A1

  公开（公告）日：2013-08-01

  Compounds of formula (I) are provided wherein R1 represents H, CN and CF3; R2 represents 1-naphthyl, 3,5-dichlorophenyl, 4-(4-fluorophenylthio)phenyl or phenyl substituted with one or more substituent selected from halogen, methoxy, cyano, methyl and trifluorom ethyl; R3 and R4 independently represent H, C1-3-alkyl or R3 and R4 together with the carbon atom to which they are attached form a C4-6-cyclic alkyl; R5 and R6 independently represent H or C1-6-alkyl; n represents 1 or 2; and pharmaceutically acceptable acid addition salts thereof, provided that if n is 2 then R2 is not 1-naphthyl, which compounds are selective allosteric SERT ligands.

  提供具有以下式（I）的化合物，其中R1代表H、CN和CF3；R2代表1-萘基、3,5-二氯苯基、4-(4-氟苯硫基)苯基或苯基，其上取代一个或多个取代基，所选取代基包括卤素、甲氧基、氰基、甲基和三氟甲基；R3和R4独立地代表H、C1-3-烷基或R3和R4与它们连接的碳原子一起形成C4-6-环烷基；R5和R6独立地代表H或C1-6-烷基；n代表1或2；以及其药学上可接受的酸盐，但若n为2，则R2不是1-萘基，这些化合物是选择性的别构SERT配体。