Synthesis, Computational Insights, and Evaluation of Novel Sigma Receptors Ligands.

ABSTRACT: The development of diazabicyclo[4.3.0]nonane and 2,7-diazaspiro[3.5]nonane derivatives as sigma receptors (SRs) ligands is reported. The compounds were evaluated in S1R and S2R binding assays, and modeling studies were carried out to analyze the binding mode. The most notable compounds, 4b (AD186, K_iS1R = 2.7 nM, K_iS2R = 27 nM), 5b (AB21, K_iS1R = 13 nM, K_iS2R = 102 nM), and 8f (AB10, K_iS1R = 10 nM, K_iS2R = 165 nM), have been screened for analgesic effects in vivo, and their functional profile was determined through in vivo and in vitro models. Compounds 5b and 8f reached the maximum antiallodynic effect at 20 mg/kg. The selectiv

SUBMITTER: Dichiara M 

PROVIDER: S-EPMC10197133 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature