Synthesis of substituted diphenyl sulfones and their structure–activity relationship with the antagonism of 5-НТ6 receptors
作者： Alexandre Ivachtchenko , Elena Golovina , Madina Kadieva , Oleg Mitkin , Sergei Tkachenko
DOI: 10.1016/J.BMC.2013.05.040
关键词:
摘要: Abstract Substituted diphenyl sulfones (10a–n) were synthesised, and the structures confirmed by NMR, LC–MS X-ray crystallography. Their antagonistic activities towards 5-HT6 receptor assessed in a cell-based functional assay. Diphenyl sulfone 10a, spite of being smallest simplest known sulfonyl-containing 5-HT6R antagonist, showed strong potency (Ki = 1.6 μM). Its derivative with methylamine substituent, 10g (N-methyl-2-(phenylsulfonyl)aniline), was ∼66-times as active (Ki = 24.3 nM). Addition piperazinyl moiety para-position relative to sulfonyl group compound 10m (N-methyl-2-(phenylsulfonyl)-5-piperazin-1-ylaniline) led further 150-fold increase (Ki = 0.16 nM) block serotonin-induced response HEK-293 cells that stably transfected human recombinant receptor.
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