bis-pyridinium cyclophanes: Novel ligands with high affinity for the blood-brain barrier choline transporter

bis-pyridinium cyclophanes: Novel ligands with high affinity for the blood-brain barrier choline transporter

Zhang Z F; Lockman P R; Mittapalli R K; Allen D D; Dwoskin L P; Crooks P A

Bioorganic & Medicinal Chemistry Letters

2008

2008-10

A series of bis-pyridinium cyclophane analogs designed as conformationally restricted bis-quaternary ammonium compounds were evaluated for their affinity for the blood-brain barrier (BBB) choline transporter. All the cyclophanes investigated exhibited high affinity compared to choline. Of these compounds, N, N'-(1,10-decanediyl)3,3'-(1,9-decadiyn-1,10-diyl)-bis-pyridinium diiodide (5c) and N, N'-(1,9-nonanediyl) 3,3'-(1,9-decadiyn-1,10-diyl)-bis-pyridinium dibromide (5b) exhibited highest affinity with K(i) values of 0.8 mu M and 1.4 mu M, respectively, and constitute some of the most potent BBB choline transporter ligands reported. (C) 2008 Elsevier Ltd. All rights reserved.

12-diyl-bis-3-picolinium dibromide; acetylcholine receptor; ammonium-salts; blood-brain barrier choline transporter; carrier-mediated transport; Chemistry; drug delivery; evoked dopamine release; extracellular dopamine; hyperactivity; inhibition; n; n-alkylnicotinium analogs; n'-dodecane-1; nicotinic; nicotinic receptor antagonists; Pharmacology & Pharmacy; quaternary; quaternary ammonium

Journal Article

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5622-5625

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