The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands

Ren Rui Teng, Lan Qin Bai, Chyng Yann Shiue, Stephen L. Dewey, Carroll D. Arnett, Alfred P. Wolf, Robert Hitzemann

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)811-817
Number of pages7
JournalInternational Journal of Radiation Applications and Instrumentation.
Volume17
Issue number8
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

GABA-A Receptors
Dopamine
Corpus Striatum
Alkylation
Benzodiazepines
Ligands
Membranes
Brain
1-fluoro-3-iodopropane
SCH 23390
Bz-423

ASJC Scopus subject areas

  • Medicine(all)
  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands. / Teng, Ren Rui; Bai, Lan Qin; Shiue, Chyng Yann; Dewey, Stephen L.; Arnett, Carroll D.; Wolf, Alfred P.; Hitzemann, Robert.

In: International Journal of Radiation Applications and Instrumentation., Vol. 17, No. 8, 1990, p. 811-817.

Research output: Contribution to journalArticle

Teng, Ren Rui ; Bai, Lan Qin ; Shiue, Chyng Yann ; Dewey, Stephen L. ; Arnett, Carroll D. ; Wolf, Alfred P. ; Hitzemann, Robert. / The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands. In: International Journal of Radiation Applications and Instrumentation. 1990 ; Vol. 17, No. 8. pp. 811-817.
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abstract = "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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