Predictive Screening Model For Potential Vector-mediated Transport Of Cationic Substrates At The Blood-brain Barrier Choline Transporter
12-diyl-bis-3-picolinium dibromide; analogs; Carrier-mediated transport; central-nervous-system; Chemistry; Drug bioavailability; Drug screening; evoked dopamine; extracellular dopamine; high-affinity choline; molecular-field analysis; n; n'-dodecane-1; Nicotinic receptor antagonists; Nicotinic receptor antagonists; perfusion technique; Pharmacology & Pharmacy; Quaternary ammonium; quaternary ammonium analogs; rat; release; Smoking cessation; striatal synaptosomes
Geldenhuys W J; Manda V K; Mittapalli R K; Van der Schyf C J; Crooks P A; Dwoskin L P; Allen D D; Lockman P R
Bioorganic & Medicinal Chemistry Letters
2010
2010-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.bmcl.2009.12.079" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2009.12.079</a>
Bis-azaaromatic quaternary ammonium salts as ligands for the blood-brain barrier choline transporter
12-diyl-bis-3-picolinium dibromide; analogs; Bis-quaternary ammonium salts; Blood-brain barrier; Chemistry; Choline transporter; evoked dopamine release; extracellular dopamine; hyperactivity; mediated transport; n; n'-dodecane-1; nicotinic-receptor antagonist; nucleus-accumbens; Pharmacology & Pharmacy; rat; tobacco dependence; vector
A series of bis-azaaromatic quaternary ammonium compounds containing flexible polymethylenic linkers as well as conformationally restricted linkers were evaluated for their affinity for the blood-brain barrier choline transporter (BBB-ChT). The preliminary structure-activity relationships obtained from this study suggest that incorporating a linear, conformationally restricted linker into the molecule improves affinity for the BBB-ChT. (C) 2010 Elsevier Ltd. All rights reserved.
Zheng G R; Zhang Z F; Lockman P R; Geldenhuys W J; Allen D D; Dwoskin L P; Crooks P A
Bioorganic & Medicinal Chemistry Letters
2010
2010-06
Journal Article
<a href="http://doi.org/10.1016/j.bmcl.2010.04.098" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.04.098</a>
bis-pyridinium cyclophanes: Novel ligands with high affinity for the blood-brain barrier choline transporter
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
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.
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
Journal Article
<a href="http://doi.org/10.1016/j.bmcl.2008.08.099" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2008.08.099</a>