1027267-22-6Relevant articles and documents
Substituted benzylaminoalkylindoles with preference for the σ2 binding site
Mamolo, Maria Grazia,Zampieri, Daniele,Zanette, Caterina,Florio, Chiara,Collina, Simona,Urbano, Mariangela,Azzolina, Ornella,Vio, Luciano
, p. 2073 - 2081 (2008/12/23)
In the attempt to develop new σ ligands we synthesized a series of N-benzyl-3-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the phenyl ring. The displacement percentages of [3H]-DTG and [3H]-(+)-pentazocine determined in rat liver homogenates by these compounds at the fixed 100 nM concentration have been determined as a preliminary evaluation of their σ1 and σ2 affinity, respectively. The results suggested that the phenyl substituents may positively modulate, in comparison with the unsubstituted compound, the ability to displace [3H]-DTG from σ2 sites, whereas the same phenyl substituents reduced the displacement percentages of [3H]-(+)-pentazocine from σ1 sites. Some of these compounds were selected for radioligand binding assays. Compounds with a butylene intermediate chain displayed the greatest binding affinity for σ2 over σ1 receptors. The butylene derivative with 2,4-dimethyl substitution on the phenyl ring showed the greatest σ2 affinity (σ2Ki = 5.9 nM) and an appreciable σ2 over σ1 selectivity (σ1Ki/σ2Ki = 22). The obtained results suggest that a butylene chain separating the indole moiety from variously substituted benzylamino groups may be required to their interaction with a hypothetical secondary σ2 binding site.
