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

Abstract

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 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.

The structure of glibenclamide in the solid state

“…According to the decomposition pattern, compound C should be cyclohexyl carbamic acid ( 5 ). Our compound melts at 223–225 °C, and its mass spectrum shows two intense M + H + peaks at 225.2 and 449.4 that do not correspond to 5 (215–217 °C, M = 143.1 daltons) but to N,N ′‐dicyclohexyl urea [DCU, C 13 H 24 N 2 O, M + H + = 225.2 (the 449.4 is the dimer + H + )], a commercial product that melts at 232–233 °C. In DMSO‐ d 6 , the NHs are observed at 5.54 ( 3 J = 8.2), and the cyclohexyl protons appeared at 1.29 (m, 5H), 1.48 (m, 1H), 1.60 (m, 2H) and 1.70 (m, 2H).…”

Design, Synthesis, Biological Evaluation and SARs of Novel N‐Substituted Sulfoximines as Potential Ryanodine Receptor Modulators

“…The procedure was similar to that described in reference. [16] A mixture of 4 (0.5 mmol), CuCl (0.05 mmol), and the corresponding isocyanates (0.5 mmol) in DMF (5 mL) was stirred at room temperature overnight and poured into 50 mL of ice-water. The produced precipitate was filtered, washed with water and further purified by silica gel column chromagraphy to give compounds Il -In.…”

Design, synthesis and herbicidal activity of novel sulfonylureas containing tetrahydrophthalimide substructure

“…1-[2-Chloro-5-(3,4,5,6-tetrahydrophthalimido)phenylsulfonyl]-3-ethylurea(II-2) was synthesized as previously described [19,20] . To a solution of intermediate VII(0.51 g, 1.5 mmol) and a catalytic amount of copper(I) chloride(0.02 g, 0.2 mmol) in N,N-dimethylformamide(DMF, 5 mL) was added ethyl isocyanate(0.14 g, 1.9 mmol).…”

“…2-Chloro-5-aminobenzenesulfonamide VI was obtained through reduction of compound V with Fe/HCl in ethanol [25] , and transformed into 2-chloro-5-(3,4,5,6-tetra-hydrophthalimido)phenylsulfonamide VII by reaction with 3,4,5,6-tetrahydrophthalic anhydride in acetic acid at 110 °C [26] . Subsequently, twelve novel molecules were smoothly synthesized from intermediate VII according to previous reports(Scheme 2) [18][19][20] . All the target compounds were identified and characterized by IR, UV, 1 H NMR, 13 C NMR, MS and EA.…”