5-氟-6-[(2-亚氨基吡咯烷-1-基)甲基]尿嘧啶（TPI(F)）的合成及体外评价：一种人胸苷磷酸化酶（TP）抑制剂
Synthesis and in vitro evaluation of 5-fluoro-6-[(2-iminopyrrolidin-1-YL)methyl]uracil, TPI(F): an inhibitor of human thymidine phosphorylase (TP).
作者信息
Grierson John R, Brockenbrough J Scott, Rasey Janet S, Wiens Linda, Vesselle Hubert
机构信息
Department of Radiology, Division of Nuclear Medicine, University of Washington, Seattle, Washington, USA.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2010 Jan;29(1):49-54. doi: 10.1080/15257770903451603.
Abstract
An investigation was conducted to determine if the 5-fluoro analog of TPI (5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]uracil), a potent inhibitor of human thymidine phosphorylase (TP), has an IC(50) in a range that might allow to use it labeled for imaging of TP expression in vivo. The previously unreported fluoro analog, TPI(F), was prepared and tested against TPI and TPI(Br) using an inhibition assay of [H-3]thymidine cleavage. An assay, performed in the presence of 0.4 mg/ml of human TP, yielded IC(50) values of 2.5 nM, 2.7 nM, and 9.0 nM for TPI, TPI(Br), and TPI(F), respectively. The results indicate that further studies to develop (18)F-labeled TPI(F) as a potential radiopharmaceutical for PET imaging of TP expression in vivo are warranted.
摘要
开展了一项研究，以确定人胸苷磷酸化酶（TP）的强效抑制剂TPI的5-氟类似物（5-氯-6-[(2-亚氨基吡咯烷-1-基)甲基]尿嘧啶）的半数抑制浓度（IC50）是否处于可能允许其用于体内TP表达成像标记的范围内。制备了之前未报道的氟类似物TPI(F)，并使用[H-3]胸苷裂解抑制试验针对TPI和TPI(Br)进行测试。在存在0.4mg/ml人TP的情况下进行的一项试验，TPI、TPI(Br)和TPI(F)的IC50值分别为2.5 nM、2.7 nM和9.0 nM。结果表明，有必要进一步开展研究，开发(18)F标记的TPI(F)作为一种潜在的放射性药物，用于体内TP表达的正电子发射断层显像（PET）成像。
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