Synthesis of cis -4-guanidino- l -proline and 1-carbamimidoyl- l -proline derivatives as influenza neuraminidase inhibitors

Simple methods for synthesizing cis -4-guanidino- l -proline derivatives and 1-carbamimidoyl- l -proline derivatives as influenza neuraminidase inhibitors were developed. All of these compounds were prepared originally from l -hydroxyproline through a key intermediate. Among them, compound 4 d with the scaffold of cis -4-guanidino- l -proline was the best inhibitor. The docking studies indicated that it could interact with the active site of NA similar to the binding pattern of peramivir. These compounds and the synthetic methods could be useful for exploration of novel influenza NA inhibitors.