Radiosynthesis and preclinical investigation of 11C labelled 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime ([11C]SZV 1287).,ChemMedChem

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Radiosynthesis and preclinical investigation of 11C labelled 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime ([11C]SZV 1287).
ChemMedChem ( IF 3.6 ) Pub Date : 2020-09-16 , DOI: 10.1002/cmdc.202000389
Viktória Forgács _{1,

2} , Enikő Németh ₁ , Barbara Gyuricza _{1,

2} , Adrienn Kis _{1,

3} , Judit P Szabó _{1,

3} , Pál Mikecz ₁ , Péter Mátyus ₄ , Zsuzsanna Helyes _{5,

6} , Ádám István Horváth _{5,

6} , Tamás Kálai _{7,

8} , György Trencsényi ₁ , Anikó Fekete ₁ , Dezső Szikra ₁

Affiliation

The radiosynthesis, as well as the in vivo and ex vivo biodistribution of the ¹¹C radiolabelled 3‐(4,5‐diphenyl‐1,3‐oxazol‐2‐yl)propanal oxime (6, [¹¹C]SZV 1287) are reported. SZV 1287 is a novel semicarbazide‐sensitive amine oxidase (SSAO) inhibitor and a promising candidate to be a novel analgesic for the treatment of neuropathic pain. Its radiolabelling was developed via a four‐step radiosynthesis which started from the reaction of a Grignard reagent with [¹¹C]CO₂ to produce [¹¹C]oxaprozin (3). In the next step this carboxylic acid 3 was directly reduced to yield the corresponding aldehyde, which was then converted into the oxime. [¹¹C]SZV 1287 was administered to male NMRI mice. The animals were examined with dynamic PET/MR imaging for 90 minutes. Biodistribution studies were performed at 10, 30, 60 and 120 minutes post injection. The accumulation of the labelled compound was observed in the brain of the animals. The main excretion pathway was found to be through the liver and intestines. These studies provide preliminary information for pharmacokinetic characterization of the SZV 1287.

中文翻译：

11C 标记的 3-(4,5-diphenyl-1,3-oxazol-2-yl) 丙醛肟 ([11C]SZV 1287) 的放射合成和临床前研究。

¹¹ C 放射性标记的 3-(4,5-二苯基-1,3-恶唑-2-基)丙醛肟 ( 6 , [ ¹¹ C]SZV 1287) 的放射合成以及体内和体外生物分布是报道。SZV 1287 是一种新型氨基脲敏感性胺氧化酶 (SSAO) 抑制剂，有望成为治疗神经性疼痛的新型镇痛剂。其放射性标记是通过四步放射合成开发的，该合成从格氏试剂与 [ ¹¹ C]CO ₂反应生成 [ ¹¹ C] 恶丙嗪 ( 3 ) 开始。在下一步该羧酸3直接还原生成相应的醛，然后将其转化为肟。[ ¹¹ C]SZV 1287被施用于雄性NMRI小鼠。用动态 PET/MR 成像检查动物 90 分钟。在注射后 10、30、60 和 120 分钟进行生物分布研究。在动物的脑中观察到标记化合物的积累。发现主要的排泄途径是通过肝脏和肠道。这些研究为 SZV 1287 的药代动力学特征提供了初步信息。

更新日期：2020-09-16

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