Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment

Abstract

The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline, and their exogenous agonists, of neuronal cholinergic receptors and/or acting as cholinesterase inhibitors and/or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. galanthamine, narwedine and lycoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as ''pro-drugs'', in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. Compounds of this invention may be used as medicaments.

Description

Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases associated with cognitive impairment technical field The present invention relates to compounds that, in addition to promoting the sensitivity of neuronal cholinergic receptors to acetylcholine and choline and agonists thereof and / or acting as cholinesterase inhibitors and / or neuroprotectants, have enhanced blood activity compared to their parent compounds. Brain Barrier Permeability Compounds. The compound is derived (either formally according to its chemical structure or directly by chemical synthesis) from natural compounds belonging to the alkaloid family Amaryllidaceae, such as Galanthamine, Narwedine and Lycoramine ), or a metabolite derived from said compound. The compounds of the present invention can interact with their target molecules themselves, or they can act as "prodrugs", which, after reaching their target area in the body, are converted to the original parent c...

AI Technical Summary

Problems solved by technology

However, no concept for increasing the permeability of compound

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