(1,4-diazepan-1-yl)(naphthalen-1-yl)methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1,4-diazepan-1-yl)(naphthalen-1-yl)methanone
• 英文别名: 4-(1-Naphthoyl)homopiperazine；1-(Naphthalene-1-carbonyl)-1,4-diazepane；1,4-diazepan-1-yl(naphthalen-1-yl)methanone
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: NIPZOEIYGROZLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1,4-diazepan-1-yl)(naphthalen-1-yl)methanone 、 2,4-二甲基苯甲醛 在 sodium cyanoborohydride 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以40%的产率得到(4-(2,4-dimethylbenzyl)-1,4-diazepan-1-yl)(naphthalen-1-yl)methanone
  参考文献：
  名称：

  Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands

  摘要：

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.

  DOI：

  10.1021/acsmedchemlett.9b00524
• 作为产物：
  描述：

  1,4-二氮杂环庚烷-1-甲酸叔丁酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (1,4-diazepan-1-yl)(naphthalen-1-yl)methanone
  参考文献：
  名称：

  Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands

  摘要：

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.

  DOI：

  10.1021/acsmedchemlett.9b00524

文献信息

• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05736539A1

  公开（公告）日：1998-04-07

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras. The compounds of formula A are representative of the compounds of the present invention: ##STR1##

  本发明涉及抑制法尼酰蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼酰化的化合物。本发明还涉及包含本发明化合物的化疗组合物以及抑制法尼酰蛋白转移酶和致癌基因蛋白Ras的方法。式A的化合物代表本发明的化合物：##STR1##
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO. INC.

  公开号：EP0703905A1

  公开（公告）日：1996-04-03
• US5736539A
  申请人：——

  公开号：US5736539A

  公开（公告）日：1998-04-07
• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYLE-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1995000497A1

  公开（公告）日：1995-01-05

  (EN) The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.(FR) L'invention concerne des composés inhibiteurs de farnésyle-protéine transférase (Ftase) et la farnésylation de la protéine d'oncogène Ras. L'invention concerne en outre des compositions chimiothérapiques contenant les composés de l'invention, des procédés d'inhibition de farnesyle-protéine transférase et la farnésylation de la protéine d'oncogène Ras.
• Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands
  作者：Daniele Zampieri、Sara Fortuna、Antonella Calabretti、Maurizio Romano、Renzo Menegazzi、Dirk Schepmann、Bernhard Wünsch、Maria Grazia Mamolo

  DOI：10.1021/acsmedchemlett.9b00524

  日期：2020.5.14

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.