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GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-11-08 , DOI: 10.1021/acs.jmedchem.1c01269
Sjoukje van der Hoek 1 , Inês F Antunes 2 , Khaled A Attia 2, 3 , Olivier Jacquet 3 , Andre Heeres 3, 4 , Marian Bulthuis 5 , Rolf Zijlma 2 , Hendrikus H Boersma 1 , Harry van Goor 5 , Ton J Visser 3 , Hiddo J L Heerspink 1 , Philip H Elsinga 2 , Jasper Stevens 1
Affiliation  

Inhibition of the sodium–glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [18F]canagliflozin was developed via a Cu-mediated 18F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [18F]canagliflozin with a yield of 0.5–3% (n = 4) and a purity of >95%. Autoradiography showed [18F]canagliflozin binding in human kidney sections containing SGLT2. Since [18F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.

中文翻译:

[18F] Canagliflozin 的 GMP 合成,一种用于钠-葡萄糖协同转运蛋白 2 的新型 PET 示踪剂

卡格列净在 2 型糖尿病中对钠-葡萄糖协同转运蛋白 2 (SGLT2) 的抑制作用会导致患者之间的临床反应差异很大。为了更好地理解这种可变性,正电子发射断层扫描 (PET) 示踪剂 [ 18 F]canagliflozin 是通过对其硼酸酯前体进行 Cu 介导的18 F-氟化而开发的,放射化学产率为 2.0 ± 1.9%,纯度 > 95 %。GMP 自动化合成源自 [ 18 F]canagliflozin,产率 0.5–3% ( n = 4),纯度 >95%。放射自显影显示 [ 18 F]canagliflozin 在含有 SGLT2 的人肾切片中结合。由于 [ 18F]canagliflozin 是广泛表征的药物 canagliflozin 的同位素体,因此具有其毒理学和药理学特征,使其能够立即用于患者。
更新日期:2021-11-25
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