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As a continuation of our previous work, which resulted in the identification of a new hit compound as an HIV-1 integrase inhibitor, three novel series of salicylic acid derivatives were synthesized using three versatile and practical synthetic strategies and were assayed for their capacity to inhibit the catalytic activity of HIV-1 integrase. Biological evaluations revealed that some of the synthesized compounds possess good inhibitory potency in enzymatic assays and are able to inhibit viral replication in MT-4 cells at low micromolar concentrations. Finally, docking studies were conducted to analyze the binding mode of the synthesized compounds within the DNA binding site of integrase in order to refine their structure-activity relationships.

An optimized procedure for the direct and regioselective arylationof 2-acylfurans has been developed. The versatility of this protocolhas been evaluated on a series of aryl and heteroaryl halides, thusobtaining a small collection of 2,5-disubstituted furans in moderateto good yields. Finally, the optimized protocol has been successfullyapplied to the synthesis of the HIV-1 integrase inhibitor 3 and could be further exploited for thegeneration of novel substituted furans as potential integrase inhibitors.

A novel compound inhibiting HIV-1 integrase has been identified by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with some of the compounds possessing micromolar activity both in enzymatic and cellular assays. ispartof: Bioorganic & Medicinal Chemistry Letters vol:19 issue:13 pages:3615-3618 ispartof: location:England status: published

A novel protocol for the direct and regioselective synthesis of 2,5-disubstituted furans via Heck-coupling reaction is described.

A semicorrin model system was prepared via a novel twofold Paal-Knorr type cyclization of a tetracarbonyl precursor which was obtained from an aldol reaction between virtually identical partners, readily available from one and the same precursor.

Heck-type 4-exo-trig cyclization of linear 2-enol triflate-1,5-hexadienes provides functionalized methylene cyclobutanes. Intramolecular palladium coordination can initiate β-hydride elimination leading to 1,2-dimethylene cyclobutane derivatives, which are obtained with high selectivity if substrates having a geminal diphenyl group at Cα are used. In parallel, formal 5-endo-trig cyclization and β-hydride elimination form 1-methylene cyclopent-2-en derivatives.

Heck-type 4-exo-trig cyclization of linear 2-enol triflate-1,5-hexadienes provides functionalized methylene cyclobutanes. Intramolecular palladium coordination can initiate beta-hydride elimination leading to 1,2-dimethylene cyclobutane derivatives, which are obtained with high selectivity if substrates having a geminal diphenyl group at Calpha are used. In parallel, formal 5-endo-trig cyclization and beta-hydride elimination form 1-methylene cyclopent-2-en derivatives.

A semicorrin model system was prepared via a novel twofold Paal-Knorr type cyclization of a tetracarbonyl precursor which was obtained from an aldol reaction between virtually identical partners, readily available from one and the same precursor.