Synthesis of fluorine‐18 labeled sulfonureas as β‐cell imaging agents

Abstract

AbstractTolbutamide (1) and glyburide (7) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine‐18 labeled analogs, 1‐[(4‐[18F]fluorobenzenesulfonyl)]‐3‐butyl]urea (p‐[18F]fluorotolbutamide, 3a) and N‐{4‐[β‐(2‐[18F]fluoroethoxybenzene carboxamido)ethyl]benzenesulfonyl}‐N′‐cyclohexylurea (2‐[18F]fluoroethoxyglyburide, 6a) as β‐cell imaging agents. Compound 3a was synthesized via two approaches: One‐step synthesis via nucleophilic substitution of p‐nitrotolbutamide (2) with K[18F]/Kryptofix 2.2.2 in either CH3CN or DMSO gave a complicated mixture; a two‐step synthesis via preparation and reaction of 4‐[18F]fluorobenzenesulfonamide with butyl isocyanate in the presence of either copper (I) chloride or borontrifluoride etherate complex in CH3CN followed by HPLC purification yielded compound 3a in an overall yield of 1–2% with a synthesis time of 120 minutes from EOB. Compound 6a was synthesized by alkylation of the corresponding hydroxy precursor (5) with [18F]fluoroethyl tosylate in DMSO at 120°C for 20 minutes followed by HPLC purification in an overall yield of 5–10 % with a synthesis time of 100 minutes from Copyright © 2001 John Wiley & Sons, Ltd.