57334-90-4Relevant academic research and scientific papers
Synthesis and First Evaluation of New 18F-Labelled Sulfonylureas for the Determination of the Beta-Cell Status In Vivo
Schirrmacher, R.,Shiue, G.,Shiue, S. J.,Alavi, A.,Feilen, P. J.,Schneider, S.,Beyer, J.,Roesch, F.
, p. S418 - S420 (2007/10/03)
The syntheses and first in vitro evaluations for two fluoride bearing sulfonylurea derivatives are reported. Firstly, the tolbutamide derivative 1-[4-(2-[18F]fluoroethoxy)benzenesulfonyl]-3-butyl urea (2-[18F]fluoroethyltolbutamide) could be labeled efficiently with [18F]fluoride. Subsequently, the glibenclamid derivative N-(2-(4-(N-((cyclohexylamino)carbonyl)sulfonylamino)phenyl)ethyl) 2-(5-chloro-2-[18F]fluoroethoxy)phenyl formamide (2-[18F]fluoroethyl-glibenclamide) was labeled with [18F]fluoride in high yields. Its ability to induce insuline secretion from rat beta-cells in relation to the original glibenclamide was determined.
Synthesis of fluorine-18 labeled sulfonureas as β-cell imaging agents
Wiltshire,Prior,Dhesi,Maile
, p. 127 - 139 (2007/10/03)
Tolbutamide (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 1200C for 20 minutes followed by HPLC purification in an overall yield of 5-10% with a synthesis time of 100 minutes from EOB. The lipid/water partition coefficient of compounds 3a and 6a was 3.13±0.28, n=6 and 124.33±21.61, n=8, respectively. The feasibility of using these radiotraces as β-cell imaging agents is under evaluation.
