Quinlobelane: A water-soluble lobelane analogue and inhibitor of VMAT2

Replacing the phenyl rings of the VMAT2 inhibitor, lobelane with pyridyl, quinolyl and indolyl rings affords analogues with improved water solubility. The synthetic studies reported herein underscore the paucity of hydrogenation methods that offer selectivity between different classes of heteroaromatic lobelane analogues. Quinolyl rings were found to be the only replacement for the phenyl rings in lobelane that resulted in retention of VMAT2-inhibitory properties.