Radiosynthesis and Preclinical Investigation of 11C‐Labelled 3‐(4,5‐Diphenyl‐1,3‐oxazol‐2‐yl)propanal Oxime ([11C]SZV 1287)

• Published in: ChemMedChem Vol. 15; no. 24; pp. 2470 - 2476
• Main Authors: Forgács, Viktória, Németh, Enikő, Gyuricza, Barbara, Kis, Adrienn, Szabó, Judit P., Mikecz, Pál, Mátyus, Péter, Helyes, Zsuzsanna, Horváth, Ádám István, Kálai, Tamás, Trencsényi, György, Fekete, Anikó, Szikra, Dezső
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 15.12.2020
• Subjects: Aldehydes; Analgesics; Animals; Carbon dioxide; carbon-11; Carboxylic acids; imaging agents; Intestine; in vivo biodistribution; Magnetic resonance imaging; Neuralgia; Neuroimaging; Oxazol; Pain; Pharmacokinetics; Positron emission; Positron emission tomography; Propionaldehyde; radiochemistry; Radiolabelling; Reagents; Semicarbazide; Tomography
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202000389

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. Neuropathic pain relief: A radiosynthesis has been developed for the preparation of 11C‐labelled semicarbazide‐sensitive amine oxidase inhibitor SZV 1287. This radiolabelled compound was evaluated by in vivo dynamic PET/MR imaging and ex vivo biodistribution studies. [11C]SZV 1287 was found to accumulate in the brain of NMRI mice and to be excreted through the liver. These studies provide preliminary details for the development of analgesic drug candidate SZV 1287.