Radioisotope Research Group, Nuclear Science Research School, NSTRI, Tehran, Iran.
Eur J Med Chem. 2013 Jun;64:488-97. doi: 10.1016/j.ejmech.2013.04.013. Epub 2013 Apr 12.
This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM).
本研究呈现了一系列新型芳基烷基/芳基烷基磺酰基哌嗪和哌啶基衍生物作为 sigma 受体配体的合成和生物评价。研究发现，一些卤代磺酰胺对 σ1 和 σ2 受体具有相对较高和较低的亲和力。还发现，四种哌啶衍生物的 σ1 亲和力和亚型选择性通常与哌嗪类似物相当。与 n = 0 和 2 的 σ1-Rs 化合物相比，n = 1 的化合物通过表现出更高的亲和力，被证明具有最佳的碳链长度。在该系列中，鉴定出具有 96 倍 σ1/σ2 选择性比的 4-苄基-1-(3-碘代苄基磺酰基)哌啶 sigma 配体（Kiσ1 = 0.96 ± 0.05 nM 和 Kiσ2 = 91.8 ± 8.1 nM）。
