Dai Qiu-yun
2011
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Quality indicators
Journal
Chinese Journal of Medicinal Chemistry
Abstract
CCR5 is a major co-receptor for HIV-1 entry into human cells and is also a good target for anti-HIV-1 drug design.Based on the chemical structure of Vicriviroc,a CCR5 antagonist,a series of new compounds were designed by changing its piperazine loop and other group substitutions.In the present study,15 bicyclic piperidine-based compounds were synthesized using a convergent synthetic route,and the structures of the target compounds were confirmed by MS and 1H-NMR.The synthetic routes were as follows:N-Boc-piperidine-4-carboxylic acid,N-Boc-pyrro-3-carboxylic acid and N-Boc-ethylenediamine were coupled with the amine derivatives to give the corresponding compounds 1a-1d,2a-2c,3a-3c,4-piperidinone hydrochloride reacted with 2,6-dimethylbenzoyl chloride,2,6-dichlorobenzoyl chloride and 2,4,6-trimethyl-5-pyrimidine carbonyl chloride to obtain the compounds 4a-4c.Then 4a-4c was reacted with 1a-1d,2a-2c,3a-3c to give the target compounds Ⅰ1-Ⅰ15.Furthermore,the antiviral activity and cell cytotoxicity of these compounds were evaluated with HIV-1 R5 strain in vitro.The results showed that all the target compounds exhibited potent antiviral activity against HIV-1 R5 strain(IC50=1.20-66.24 μmol · L-1).Preliminary analysis of the structure-activity relationship showed that some compounds with an aryl group and the 1,3-diamino-propane structure between two N atoms exhibited improved anti-HIV-1 activity.This study provides several clues for designing new anti-HIV-1 fusion inhibitors.