Synthesis of iodine-125 labeled 3-quinuclidinyl 4′-iodobenzilate

Kabalka, George W.; Gai, Ying; Mathur, S. B.

doi:10.1016/0883-2897(89)90099-8

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“…The mixture was diluted with chloroform (100 mL), washed with water (100 mL), and dried over sodium sulfate to afford a yellow oil upon evaporation of the solvent. The product was purified by silica column chromatography by initial elution with chloroform containing 1.0% ammonium hydroxide to remove tributyltin hydride followed by chloroform/methanol/ ammonium hydroxide (95:5:1) to afford 6 as a pale yellow oil (550.4 mg, 40.3%): *H NMR (CDC13) S 7.62-7.58 (m, 2 H), 7.37-7.25 (m, 3 H), 6.17-5.89 (m, 2 H), 4.83-4.75 (m, 1 H), 4.10 (bs, 1 H), 3.25-3.03 (m, 2 H), 2.91-2.67 (m, 6 H), 2.03-1.90 (m, 1H), 1.67-1.17 (m, 16 H), 0.97-0.67 (m, 15 H); I3C NMR (CDC13) 5 174.25 (CO), 142.22 (CH), 141.55 (C), 133.94 (CH), 127.94 (CH), 127.48 (CH), 125.45 (CH), 77.12 (C), 73.51 (CH), 50.03 (CH2), 48.01 (CH2), 47.27 (CH2), 46.31 (CH2), 29.02 (CH2), 27.24 (CH2), 25.01 (CH), 24.31 (CH2), 19.41 (CH2), 13.70 (CH3), 9.49 (CH2); TLC (silica, 10% chloroform/ methanol) Rf -0.50. 1-Azabicyclo[2.2.2]oct-3-yl a-Hydroxy-a-( 1-iodo-1-propen-3-yl)-a-phenylacetate (3).…”

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confidence: 99%

Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl .alpha.-hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography

McPherson¹,

DeHaven‐Hudkins²,

Callahan³

et al. 1993

J. Med. Chem.

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1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha-phenylacetate (IQNP, 3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity [125]IQNP ([125I]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide. In in vitro receptor binding studies, 3 demonstrated high affinity for M1 (Ki = 0.78 nM), M2 (Ki = 1.06 nM), and M3 (Ki = 0.27 nM) subtypes. In vivo biodistribution studies in female rats [125I]-3 demonstrated high uptake in areas rich in muscarinic receptors such as the brain (cortex and striatum) and the heart. Blocking studies were performed with a series of receptor specific agents and demonstrated that the uptake of [125I]-3 was selective and specific for cerebral muscarinic receptor rich areas and that the binding to m-AChR is reversible. The high-yield preparation and specificity and selectivity of high specific activity [125I]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT).

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