Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs—edaravone and riluzole—have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone—phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.

New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC₅₀: AChE, 0.265−4.24 μM; BChE, 0.01−0.64 μM) but poor activity against off‐target carboxylesterase (CES). Specifically, conjugates with a (CH₂)₈ spacer showed the highest AChE and BChE inhibition: 3–16 times more effective than amiridine. Salicylamides 7b and 7c had the maximum BChE/AChE selectivity ratios: 193 and 138, respectively. Conjugates were mixed‐type reversible inhibitors of both cholinesterases and displaced propidium from the AChE peripheral anionic site (PAS) at the level of donepezil. All conjugates inhibited Aβ₄₂ self‐aggregation in the thioflavin test; inhibition increased with spacer elongation, being greatest for (CH₂)₈. The results agreed with molecular docking to AChE, BChE, and Aβ₄₂. Conjugates exhibited high 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS)^•+‐scavenging activity comparable to the standard antioxidant Trolox, and they showed the ability to bind Cu²⁺, Fe²⁺, and Zn²⁺. Conjugates had favorable predicted intestinal absorption and blood–brain barrier permeability. Altogether, the results indicate that the new conjugates possess potential for further development as multifunctional anti‐AD drug candidates.