tert-butyl 4-(4-(pyridin-4-yl)phenyl)piperazine-1-carboxylate | 1202880-76-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(4-(pyridin-4-yl)phenyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-(4-pyridin-4-ylphenyl)piperazine-1-carboxylate
• CAS: 1202880-76-9
• 化学式: C₂₀H₂₅N₃O₂
• 分子量: 339.437
• InChiKey: TWKIBAAVSJKWGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(pyridin-4-yl)phenyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以74.66 %的产率得到1-(4-(pyridin-4-yl)phenyl)piperazine
  参考文献：
  名称：

  发现新型联苯衍生物作为雄激素受体降解剂，用于治疗恩杂鲁胺耐药性前列腺癌

  摘要：

  第二代AR拮抗剂，例如恩杂鲁胺，是晚期前列腺癌的主要治疗药物。然而，原发性和继发性耐药性的发展导致治疗失败和患者死亡。同时拮抗和降解 AR 的双功能药物可以更完全地阻断 AR 信号通路，并对野生型和耐药性前列腺癌细胞表现出优异的抗增殖活性。在这里，我们报道了一系列作为雄激素受体拮抗剂和降解剂的联苯衍生物的发现和优化。这些联苯衍生物对 LNCaP 和 22Rv1 细胞表现出有效的抗增殖活性。我们的发现丰富了小分子 AR 降解剂的多样性，并为开发用于治疗恩杂鲁胺耐药性前列腺癌的新型 AR 降解剂提供了见解。

  DOI：

  10.1016/j.bioorg.2024.107433
• 作为产物：
  描述：

  吡啶-4-硼酸 、 4-(4-碘苯基)四氢-1(2H)-吡嗪羧酸叔丁酯 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 1.0h， 以43%的产率得到tert-butyl 4-(4-(pyridin-4-yl)phenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol

  摘要：

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-{[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.025

文献信息

• [EN] AMIDE COMPOUND AND USE THEREOF<br/>[FR] COMPOSÉ AMIDE ET SON APPLICATION<br/>[ZH] 酰胺类化合物及其应用
  申请人：UNIV CHINA PHARMA

  公开号：WO2023011596A1

  公开（公告）日：2023-02-09

  一种式(I)所示化合物或其立体异构体或药学上可接受的盐，含有它们的药物组合物，以及它们作为选择性雄激素受体降解剂(SARD)和/或雄激素受体(AR)拮抗剂的用途，特别适用于制备用于治疗或预防由雄激素受体介导的疾病的药物。
• Development of (<i>S</i>)-<i>N</i>⁶-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-<i>N</i>⁶-propyl-4,5,6,7-tetrahydrobenzo[<i>d</i>]-thiazole-2,6-diamine and Its Analogue as a D3 Receptor Preferring Agonist: Potent in Vivo Activity in Parkinson’s Disease Animal Models
  作者：Balaram Ghosh、Tamara Antonio、Juan Zhen、Prashant Kharkar、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm901184n

  日期：2010.2.11

  Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out, Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K-i). Functional activity of selected compounds in stimulating GTP gamma S binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. SAR results identified compound (-)-24c (D301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.
• Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol
  作者：Balaram Ghosh、Tamara Antonio、Bhaskar Gopishetty、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2010.06.025

  日期：2010.8

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.
• 10.1016/j.bioorg.2024.107433
  作者：Zhang, Wenqiang、Fan, Yawen、Zhang, Yan、Feng, Yunrui、Luo, Yi、Zhou, Xiaoyu、Chen, Zhuolin、Wang, Chenxiao、Lu, Tao、Tang, Feng、Chen, Yadong、Li, Hongmei、Jiao, Yu

  DOI：10.1016/j.bioorg.2024.107433

  日期：——

  agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery

  第二代AR拮抗剂，例如恩杂鲁胺，是晚期前列腺癌的主要治疗药物。然而，原发性和继发性耐药性的发展导致治疗失败和患者死亡。同时拮抗和降解 AR 的双功能药物可以更完全地阻断 AR 信号通路，并对野生型和耐药性前列腺癌细胞表现出优异的抗增殖活性。在这里，我们报道了一系列作为雄激素受体拮抗剂和降解剂的联苯衍生物的发现和优化。这些联苯衍生物对 LNCaP 和 22Rv1 细胞表现出有效的抗增殖活性。我们的发现丰富了小分子 AR 降解剂的多样性，并为开发用于治疗恩杂鲁胺耐药性前列腺癌的新型 AR 降解剂提供了见解。