Rasagiline derivatives combined with histamine H receptor properties.

The irreversible monoamine oxidase B (MAO B) inhibitor rasagiline has been described with multiple disease modifying effects in vitro on models of Parkinson's disease. The combination of this established drug to recently developed histamine H receptor (HR) antagonist elements gives new impetus to the design of multitargeting ligands. Surprisingly, the 5-substituted 3-piperidinopropyloxy rasagiline derivative 1 was more potent on both targets than its 6-substituted isomer. It showed nanomolar affinities at the desired targets (MAO B IC = 256 nM; hHR K = 2.6 nM) with a high preference over monoamine oxidase A (MAO A) and negligible affinity at histamine H, H, dopamine D, D receptors or acetyl-/butyrylcholinesterases.