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• 1310743-76-0 2-[2-(1-hydroxy-4-oxocyclohexyl)phenyl]acetaldehyde dimethyl acetal 
• 1310743-77-1 3-methoxy-3,4-dihydrospiro[[2]benzopyran-1,1'-cyclohexan]-4'-one 
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• 130089-19-9 1-bromo-2-(2-methoxyethenyl)benzene 
• 6630-33-7 ortho-bromobenzaldehyde 

Relevant academic research and scientific papers

Design, synthesis and pharmacological evaluation of spirocyclic σ1 receptor ligands with exocyclic amino moiety (increased distance 1)

Various pharmacophore models for potent σ1 ligands specify a basic amino group flanked by two different hydrophobic regions in defined distances to the basic amine (distance 1 and distance 2, respectively). According to these models distance 1 of the potent spirocyclic σ1 ligand 1 is too short. In order to find a new class of more potent σ1 ligands and to verify the distance hypothesis of the pharmacophore models spirocyclic compounds 2 with an exocyclic amino group were designed and synthesized. The secondary amines 8 and 9 with N-benzyl residues are >100-fold less potent than the spirocyclic piperidine 1. However, the tertiary methylamines trans-11 and cis-11 represent potent σ1 ligands with Ki-values of 43 and 24 nM, respectively. Whereas one large benzyl moiety is required for high σ1 receptor binding, a second large N-substituent is not tolerated by the σ1 receptor protein. As a rule, cis-configured diastereomers with a longer distance 1 (predominantly 7.16-7.23 ) show higher σ1 affinities than their trans-configured counterparts (distance 1 is predominantly 5.88-6.26 ).