Novel furocoumarins as potential HIV-1 integrase inhibitors

• An HIV-1 IN active site model was constructed using sub-domain X-ray and NMR structures.
• The model was used to identify a furocoumarin system as a potential HIV-1 IN inhibitor.
• The potential HIV-1 IN inhibitor and six structural analogues have been synthesised.
• Some of the furocoumarin ligands exhibit low but statistically significant inhibition at 10 μM.

A series of seven novel, rationally designed N-substituted 3-{3,5-dimethylfuro[3,2-g]coumarin-6-yl}propanamides have been prepared as potential HIV-1 integrase (IN) inhibitors via a five-step pathway commencing with resorcinol and diethyl 2-acetylglutarate, and the HIV-1 IN inhibition potential of these compounds has been examined relative to raltegravir, a known HIV-1 IN inhibitor.

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