کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1370619 | 981823 | 2011 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT6 receptor ligands Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT6 receptor ligands](/preview/png/1370619.png)
A series of N1-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N1-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT6 receptor. Several compounds displayed potent binding affinity for the 5-HT6 receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C3 of indole carbon maintains the binding affinity to 5-HT6R. The lead compound N1-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb = 0.1 nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze.
Design, synthesis, SAR, pharmacokinetic and pharmacological profile of a series of N1-arylsulfonyl-3-pyrrolidinyl indoles as potent and selective 5-HT6R antagonists was presented. The lead compound N1-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb = 0.1 nM) was active in animal models of cognition.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 15, 1 August 2011, Pages 4577–4580