During previous studies, we have developed several hybrid compounds combining tetrahydropyrans with oxa and thiazols. These compounds exhibited interesting selective antiproliferative activity against a set of human tumour cell lines. As part of our process to produce new compounds with better activity, we decided to simplify the structures and substitute the building block less active (oxazole). Therefore, we used the on-line software LLAMA (Lead-Likeness And Molecular Analysis) to generate a library of compounds and theoretically evaluate their properties to be a potential lead compound. LLAMA software generates new compounds adding different “decorations” into a base structure. After comparing some of the compounds with anticancer products from the literature, we proposed a new series of hybrid compounds to be prepared, combining tetrahydropyrans wit different aromatic rings and N-heterocycles.