TY - JOUR
T1 - The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands
AU - Teng, Ren Rui
AU - Bai, Lan Qin
AU - Shiue, Chyng Yann
AU - Dewey, Stephen L.
AU - Arnett, Carroll D.
AU - Wolf, Alfred P.
AU - Hitzemann, Robert J.
N1 - Funding Information:
Acknowledgements-This research was carried out at BrookhavenN ational Laboratoryu nderc ontractw ith the U.S. Departmenot f Energya nd supportedb y its Dfhce of Health and EnvironmentalR esearcha nd also supported bv National Institute of Health Grants NS 15380a nd NS-15638.T he authors wish to thank J. S. Fowler, K. Karlstrom, P. King and D. J. Schlyer for advice and assistance.
PY - 1990
Y1 - 1990
N2 - No-carrier-added (NCA) R(+)-7-chloro-8-hydroxy-3-(3′-[18F]fluoropropyl)-1-phenyl-2,3,4,5-tetrahydro-3-benzazepine (2b) (an analog of dopamine D-1 receptor ligand SCH 23390), ethyl 8-fluoro-5,6-dihydro-5-(3′-fluoropropyl)-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (4b) and 3′-[18F]fluoropropyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (6b) (analogs of the benzodiazepine RO 15-1788) were synthesized by alkylation of the corresponding nor-compound with NCA 1-[18F]fluoro-3-iodopropane in 10-15% yield (EOB) in ~110min and with a mass of 2-3nmol. Compound 2 is less potent (~ 12-14 times) than SCH 23390 in binding to rat striatal membranes in vitro. Compounds 2b, 4b and 6b exhibit no specific anatomical distribution to mouse brain. These results suggest that the substituent at position 3 of SCH 23390, and position 5 and carboxylate group of RO 15-1788 are critical determinants both of affinity and selectivity for receptor binding, and underscores the evaluation necessary when even minor changes (C1 to C3) are made in bioactive compounds.
AB - No-carrier-added (NCA) R(+)-7-chloro-8-hydroxy-3-(3′-[18F]fluoropropyl)-1-phenyl-2,3,4,5-tetrahydro-3-benzazepine (2b) (an analog of dopamine D-1 receptor ligand SCH 23390), ethyl 8-fluoro-5,6-dihydro-5-(3′-fluoropropyl)-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (4b) and 3′-[18F]fluoropropyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate (6b) (analogs of the benzodiazepine RO 15-1788) were synthesized by alkylation of the corresponding nor-compound with NCA 1-[18F]fluoro-3-iodopropane in 10-15% yield (EOB) in ~110min and with a mass of 2-3nmol. Compound 2 is less potent (~ 12-14 times) than SCH 23390 in binding to rat striatal membranes in vitro. Compounds 2b, 4b and 6b exhibit no specific anatomical distribution to mouse brain. These results suggest that the substituent at position 3 of SCH 23390, and position 5 and carboxylate group of RO 15-1788 are critical determinants both of affinity and selectivity for receptor binding, and underscores the evaluation necessary when even minor changes (C1 to C3) are made in bioactive compounds.
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U2 - 10.1016/0883-2897(90)90030-5
DO - 10.1016/0883-2897(90)90030-5
M3 - Article
C2 - 2079428
AN - SCOPUS:0025656382
SN - 0883-2897
VL - 17
SP - 811
EP - 817
JO - International Journal of Radiation Applications and Instrumentation.
JF - International Journal of Radiation Applications and Instrumentation.
IS - 8
ER -