3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propylamine | 1194373-19-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propylamine
• 英文别名: 3-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propan-1-amine
• CAS: 1194373-19-7
• 化学式: C₁₄H₂₁NO
• 分子量: 219.327
• InChiKey: OGFUFDXKHDSKCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 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：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propylamine 、 2-氯-n-环己基-乙酰胺 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 以75%的产率得到2-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propylamino]-N-cyclohexylacetamide
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505
• 作为产物：
  描述：

  2-[3-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]isoindole-1,3-dione 在 一水合肼 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以70%的产率得到3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propylamine
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505

文献信息

• Sigma receptor ligands and methods of modulating cellular protein homeostasis using same
  申请人：DREXEL UNIVERSITY

  公开号：US10314795B2

  公开（公告）日：2019-06-11

  The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

  本发明包括可用于预防、治疗或改善西格玛相关紊乱或疾病的化合物。本发明的化合物可调节细胞蛋白质的平衡，其中包括：蛋白质的翻译起始、折叠、加工、运输和降解（包括泛素选择性自噬）。本发明还包括预防、治疗或改善有需要的受试者与 Sigma 相关的失调或疾病的方法，该方法包括向受试者施用有效量的 Sigma 调节化合物。本发明还包括预防、治疗或改善有需要的受试者的西格玛相关紊乱或疾病的方法，该方法包括向受试者施用有效量的西格玛调节化合物，进一步包括施用有效量的抑制泛素蛋白酶体系统（UPS）和/或自噬存活途径的化合物。
• METHODS OF IDENTIFYING AND TREATING TUMORS WITH SIGMA1 INHIBITORS
  申请人：DREXEL UNIVERSITY

  公开号：US20200087730A1

  公开（公告）日：2020-03-19

  Methods and uses of using Sigma1 inhibitors are provide herein, including diagnostic methods for predicting or identifying quantitatively whether a human tumor is responsive or non-responsive to treatment with Sigma1 inhibition are also provided.
• US9889102B2
  申请人：——

  公开号：US9889102B2

  公开（公告）日：2018-02-13
• [EN] NOVEL SIGMA RECEPTOR LIGANDS AND METHODS OF MODULATING CELLULAR PROTEIN HOMEOSTASIS USING SAME<br/>[FR] NOUVEAUX LIGANDS DU RÉCEPTEUR SIGMA ET PROCÉDÉS DE MODULATION DE L'HOMÉOSTASE DE PROTÉINE CELLULAIRE À L'AIDE DE CEUX-CI
  申请人：PHILADELPHIA HEALTH & EDUCATIO

  公开号：WO2014015157A2

  公开（公告）日：2014-01-23

  The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.
• [EN] METHODS OF MODULATING LEVELS OF IL-6 AND PD-L1<br/>[FR] MÉTHODES DE MODULATION DE NIVEAUX D'IL-6 ET DE PD-L1
  申请人：UNIV DREXEL

  公开号：WO2017106312A1

  公开（公告）日：2017-06-22

  Embodiments described herein provide methods of treating various diseases or disorders using Sigma1 modulating compounds alone or in combination with other therapeutic agents.