1-(5-Phenoxypentyl)piperazine | 401485-52-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(5-Phenoxypentyl)piperazine
• CAS: 401485-52-7
• 化学式: C₁₅H₂₄N₂O
• 分子量: 248.368
• InChiKey: YBPWXFPNBXLMNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(5-Phenoxypentyl)piperazine 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 26.5h， 生成 3-[4-(5-Phenoxypentyl)piperazin-1-yl]propan-1-amine;hydrochloride
  参考文献：
  名称：

  1-Phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives as non-imidazole histamine H3-antagonists

  摘要：

  In this study, a series of 1-phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives has been prepared and in vitro tested as H-3-receptor antagonists (electrically evoked contraction of the guinea pig jejunum). All compounds investigated show moderate in vitro affinities. The most potent antagonists in this series are the compounds 9b, 1b, 1f, and 1l, which exhibit, independently of the substituent at the end of -N- moiety, almost the same level of affinity (pA (2) = 7.18, pA (2) = 7.27, pA (2) = 7.13, pA (2) = 7.12, respectively). The histaminergic H-1 antagonism of the aforementioned four products was established on the isolated guinea pig ileum by conventional methods; the pA (2) values were compared with the potency of pyrilamine. None of them shows any H-1-antagonistic activity (pA (2) < 4; for pyrilamine pA (2) = 9.35).

  DOI：

  10.1007/s00044-012-0090-2
• 作为产物：
  描述：

  苯酚 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 1-(5-Phenoxypentyl)piperazine
  参考文献：
  名称：

  发现带有供体NO / H 2 S的3-正丁基邻苯二甲酸酯的开环衍生物作为潜在的抗缺血性卒中剂

  摘要：

  为了寻找比已知药物3-n-丁基邻苯二甲酸酯（NBP）更高效力的新型抗缺血性中风药，NBP的一系列开环衍生物同时带有一氧化氮（NO）和硫化氢（H 2 S）-设计，合成和生物学评估供体部分（NO / H 2 S-NBP）（8a-8o）。活性最高的化合物8d在体外抑制ADP诱导的血小板凝集方面比NBP和相应的H 2 S-NBP 10或NO-NBP 13更有效。另外，8d产生中等水平的NO和H 2S，可能有益于改善心血管和脑循环。更重要的是，在短暂性局灶性脑缺血的大鼠模型中，口服治疗8d改善了神经行为功能，减小了梗塞的大脑大小和脑水含量，并增强了脑抗氧化剂SOD，GSH和GSH-Px的水平，但降低了水平氧化剂MDA。8d对缺血/再灌注（I / R）相关的脑损伤的保护作用大于NBP，这表明8d可能是有希望进行进一步研究的药物。

  DOI：

  10.1016/j.ejmech.2016.03.044

文献信息

• Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
  申请人：Arvinas, Inc.

  公开号：US10723717B2

  公开（公告）日：2020-07-28

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作快速加速纤维肉瘤（RAF，如c-RAF、A-RAF和/或B-RAF；靶蛋白）的调节剂。特别是，本公开内容涉及双功能化合物，其一端含有与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、cereblon、抑制细胞凋亡蛋白或小鼠双敏同源物 2 配体，另一端含有与靶蛋白 RAF 结合的分子，从而将靶蛋白置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防由于靶蛋白的聚集或积聚或靶蛋白的组成性激活而导致的疾病或失调。
• New azoles with potent antifungal activity: Design, synthesis and molecular docking
  作者：Xiaoying Che、Chunquan Sheng、Wenya Wang、Yongbing Cao、Yulan Xu、Haitao Ji、Guoqiang Dong、Zhenyuan Miao、Jianzhong Yao、Wannian Zhang

  DOI：10.1016/j.ejmech.2009.05.018

  日期：2009.10

  In response to the urgent need for novel antifungal agents with improved activity and broader spectrum, computer modeling was used to rational design novel antifungal azoles. On the basis of the active site of lanosterol 14 alpha-demethylase from Candida albicans (CACYP51), a series of new azoles with substituted-phenoxypropyl piperazine side chains were rational designed and synthesized. In vitro antifungal activity assay indicates that the new azoles show good activity against most of the tested pathogenic fungi. Interestingly, the designed compounds are also active against an azole-resistant clinical strain. Compared to fluconazole and itraconazole, several compounds (such as 12i, 12j and 12n) show higher antifungal activity and broader spectrum, which are promising leads for the development of novel antifungal agents. (C) 2009 Elsevier Masson SAS. All rights reserved.
• 1-Phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives as non-imidazole histamine H3-antagonists
  作者：Marek Staszewski、Krzysztof Walczyński

  DOI：10.1007/s00044-012-0090-2

  日期：2013.3

  In this study, a series of 1-phenoxyalkyl-4-[(N,N-disubstitutedamino)alkyl]piperazine derivatives has been prepared and in vitro tested as H-3-receptor antagonists (electrically evoked contraction of the guinea pig jejunum). All compounds investigated show moderate in vitro affinities. The most potent antagonists in this series are the compounds 9b, 1b, 1f, and 1l, which exhibit, independently of the substituent at the end of -N- moiety, almost the same level of affinity (pA (2) = 7.18, pA (2) = 7.27, pA (2) = 7.13, pA (2) = 7.12, respectively). The histaminergic H-1 antagonism of the aforementioned four products was established on the isolated guinea pig ileum by conventional methods; the pA (2) values were compared with the potency of pyrilamine. None of them shows any H-1-antagonistic activity (pA (2) < 4; for pyrilamine pA (2) = 9.35).
• Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H2S-donating moieties as a potential anti-ischemic stroke agent
  作者：Wei Yin、Li Lan、Zhangjian Huang、Jing Ji、Jiangen Fang、Xiaoli Wang、Hui Ji、Sixun Peng、Jinyi Xu、Yihua Zhang

  DOI：10.1016/j.ejmech.2016.03.044

  日期：2016.6

  To search for novel anti-ischemic stroke agents with higher potency than a known drug 3-n-butylphthalide (NBP), a series of ring-opened derivatives of NBP bearing both nitric oxide (NO) and hydrogen sulfide (H2S)-donating moieties (NO/H2S-NBP) (8a-8o) were designed, synthesized, and biologically evaluated. The most active compound 8d was more potent than NBP and the corresponding H2S-NBP 10 or NO-NBP

  为了寻找比已知药物3-n-丁基邻苯二甲酸酯（NBP）更高效力的新型抗缺血性中风药，NBP的一系列开环衍生物同时带有一氧化氮（NO）和硫化氢（H 2 S）-设计，合成和生物学评估供体部分（NO / H 2 S-NBP）（8a-8o）。活性最高的化合物8d在体外抑制ADP诱导的血小板凝集方面比NBP和相应的H 2 S-NBP 10或NO-NBP 13更有效。另外，8d产生中等水平的NO和H 2S，可能有益于改善心血管和脑循环。更重要的是，在短暂性局灶性脑缺血的大鼠模型中，口服治疗8d改善了神经行为功能，减小了梗塞的大脑大小和脑水含量，并增强了脑抗氧化剂SOD，GSH和GSH-Px的水平，但降低了水平氧化剂MDA。8d对缺血/再灌注（I / R）相关的脑损伤的保护作用大于NBP，这表明8d可能是有希望进行进一步研究的药物。