Synthesis and evaluation of the anticholinesterase activity of anilidoalkylpiperazines: potential multitarget agents

Abstract

Interest in multimarket drugs, i.e. molecules capable of interacting with more than one target simultaneously, has been growing in recent years as a new strategy to treat complex diseases that involve different interconnected signaling pathways. This is the case for neuropsychiatric diseases such as Alzheimer's (AD) and Parkinson's diseases, schizophrenia, depression, epilepsy among others closely related to cognitive loss. Since the processes that lead to learning and memory formation are related to the activation of the cholinergic and histaminergic pathways, the interaction with targets present in both pathways may significantly improve cognitive processes. Diseases that cause cognitive loss, especially AD, have attracted interest from research groups, and a pleiotropic approach can be very useful in those cases. Regarding this, this project aims to synthesize and evaluate the activity of a set of anilidoalkylpiperzines with variations in the aromatic ring, the length of the alkyl chain and also in the terminal nitrogen as anticholinesterase agents and as antagonists of the histamine H3 receptor. The compounds will be prepared through methodologies developed in our research group, which generally lead to good yields. The designed series may bring important SAR information to optimize the activity of new compounds as well as in the multitarget approach.