Synthesis and Evaluation as a Blood-Brain Barrier-Permeable Probe of 7-N-(PROXYL-3-yl-methyl)theophylline

被引：8
|
作者：
Emoto, Miho C. [1 ]
Sasaki, Kota [2 ]
Maeda, Koya [2 ]
Fujii, Hirotada G. [1 ]
Sato, Shingo [2 ]
机构：
[1] Sapporo Med Univ, Ctr Med Educ, Sapporo, Hokkaido 0608556, Japan
[2] Yamagata Univ, Grad Sch Sci & Engn, Dept Biochem Engn, 4-3-16 Jonan, Yonezawa, Yamagata 9928510, Japan
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2018年 / 66卷 / 09期
基金：
日本学术振兴会;
关键词：
theophylline; pyrrolidine nitroxide; blood-brain barrier; redox status; FREE-RADICAL REACTIONS; NITROXYL-PROBES; ASCORBIC-ACID; REDUCTION; GLUTATHIONE; DISEASE; MOUSE;
D O I：
10.1248/cpb.c18-00333
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The drug-nitroxide radical hybrid-compound 7-N-((2,2,5,5-tetramethylpyrrolidine-1-yloxy(PROXYL))-3-yl-methyl)theophylline (3) was synthesized by coupling 7-N-tosyltheophylline with 3-hydroxymethyl-PROXYL, HMP). The stability of 3 relative to that of HMP was examined in the presence of the anti-oxidant, ascorbic acid (AsA). The initial reduction rate constants of 3 and HMP were 11.9 +/- 5.3 and w6.1 +/- 5.2 M-1 min(-1), respectively. In the presence of glutathione (GSH), these constants increased slightly to 22.3 +/- 6.8 and 9.1 +/- 2.4 M-1 min(-1), respectively. Two-dimensional cranial electron paramagnetic resonance imaging of mice intravenously injected with 3 via the tail vein revealed that probe 3 enters the mouse brain by passing through the blood-brain barrier (BBB).
引用
收藏
页码：887 / 891
页数：5
相关论文
共 18 条
  • [1] Novel blood-brain barrier-permeable spin probe for in vivo electron paramagnetic resonance imaging
    Wang, Xiaolei
    Emoto, Miho
    Miyake, Yusuke
    Itto, Kaori
    Xu, Shu
    Fujii, Hirotada
    Hirata, Hiroshi
    Arimoto, Hirokazu
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (20) : 4947 - 4949
  • [2] Design and synthesis of selective and blood-brain barrier-permeable hydroxamate-based gelatinase inhibitors
    Bertran, Alexandra
    Khomiak, Danylo
    Konopka, Anna
    Rejmak, Emilia
    Bulska, Ewa
    Seco, Jesus
    Kaczmarek, Leszek
    Tarrago, Teresa
    Prades, Roger
    BIOORGANIC CHEMISTRY, 2020, 94
  • [3] "Three-in-one" strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone
    Shen, Lei
    Liu, Hongmei
    Jin, Ming
    Zhang, Jinchao
    Yin, Caixia
    Wang, Shuxiang
    Yang, Yutao
    CHINESE CHEMICAL LETTERS, 2024, 35 (10)
  • [4] “Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone
    Lei Shen
    Hongmei Liu
    Ming Jin
    Jinchao Zhang
    Caixia Yin
    Shuxiang Wang
    Yutao Yang
    Chinese Chemical Letters, 2024, 35 (10) : 386 - 389
  • [5] Design, synthesis, and pharmacological evaluation of indole-piperidine amides as Blood-brain barrier permeable dual cholinesterase and β-secretase inhibitors
    Banoo, Razia
    Nuthakki, Vijay K.
    Wadje, Bhagyashri N.
    Sharma, Ankita
    Bharate, Sandip B.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 266
  • [6] Environment-Friendly Synthesis of Targeted Anticancer Drug N-(N'-Carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) and the Evaluation of Its Activity to Penetrate Blood-Brain Barrier
    Zhang, Chao
    Liu, Zhijun
    Li, Yanbing
    He, Yepu
    Lin, Xiaohong
    Chen, Heru
    CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2020, 40 (02) : 536 - 540
  • [7] Inhibitors of phenylethanolamine N-methyltransferase that are predicted to penetrate the blood-brain barrier:: Design, synthesis, and evaluation of 3-fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines that possess low affinity toward the α2-adrenoceptor
    Romero, FA
    Vodonick, SM
    Criscione, KR
    McLeish, MJ
    Grunewald, GL
    JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (18) : 4483 - 4493
  • [8] Synthesis and Biological Evaluation of Novel N-[(7-pyridin-4-yl-2, 3-dihydro-benzofuran-2-yl) Methyl]-(4-methyl-1, 2, 3-thiadiazole-5-yl) Formamide as a Potent Immunosuppressant Agent
    Fan, Chen
    Wang, Yubin
    Lu, Peng
    Xue, Xiaojian
    She, Jinxiong
    LETTERS IN DRUG DESIGN & DISCOVERY, 2014, 11 (03) : 375 - 379
  • [9] Synthesis and Initial Evaluation of YM-08, a Blood-Brain Barrier Permeable Derivative of the Heat Shock Protein 70 (Hsp70) Inhibitor MKT-077, Which Reduces Tau Levels
    Miyata, Yoshinari
    Li, Xiaokai
    Lee, Hsiu-Fang
    Jinwal, Umesh K.
    Srinivasan, Sharan R.
    Seguin, Sandlin P.
    Young, Zapporah T.
    Brodsky, Jeffrey L.
    Dickey, Chad A.
    Sun, Duxin
    Gestwicki, Jason E.
    ACS CHEMICAL NEUROSCIENCE, 2013, 4 (06): : 930 - 939
  • [10] Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus
    Hirohata, Shunsei
    Arinuma, Yoshiyuki
    Yanagida, Tamiko
    Yoshio, Taku
    ARTHRITIS RESEARCH & THERAPY, 2014, 16 (02)
12