Discovery of AD258 as a Sigma Receptor Ligand with Potent Antiallodynic Activity.

ABSTRACT: The design and synthesis of a series of 2,7-diazaspiro[4.4]nonane derivatives as potent sigma receptor (SR) ligands, associated with analgesic activity, are the focus of this work. In this study, affinities at S1R and S2R were measured, and molecular modeling studies were performed to investigate the binding pose characteristics. The most promising compounds were subjected to in vitro toxicity testing and subsequently screened for in vivo analgesic properties. Compound 9d (AD258) exhibited negligible in vitro cellular toxicity and a high binding affinity to both SRs (K_iS1R = 3.5 nM, K_iS2R = 2.6 nM), but not for other pain-related targets, and exerted high potency in a model of capsaicin-induced allodynia, reaching the m

SUBMITTER: Dichiara M 

PROVIDER: S-EPMC10461227 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature