Development of Novel Potential Pleiotropic Compounds of Interest in Alzheimer's Disease Treatment through Rigidification Strategy.

ABSTRACT: The development of Multi-Target Directed Ligand is of clear interest for the treatment of multifactorial pathology such as Alzheimer's disease (AD). In this context, acetylcholinesterase (AChE) inhibitors have been modulated in order to generate novel pleiotropic compounds targeting a second protein of therapeutic interest in AD. Among them, donecopride was the first example of a dual acetylcholinesterase inhibitor and 5-HT₄ receptor agonist. In order to explore the structural diversity around this preclinical candidate we have explored the preparation of novel constrained analogs through late-stage rigidification strategy. A series of phenylpyrazoles was prepared in a late-stage functionalization process and all compounds were evaluated in vitro towards AChE and 5-HTRs. A docki

SUBMITTER: Lecoutey C 

PROVIDER: S-EPMC8123621 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature