DESIGN AND SYNTHESIS OF NOVEL SCAFFOLDS AND BUILDING BLOCKS

Medicinal chemistry focuses on the aspect related to the structural design, synthesis and identification of therapeutically interesting compounds, i.e. pharmaceuticals, as well as the molecular reasons of their mechanism of action, including the understanding of the factors involved in the structure-activity relationships, absorption, distribution, metabolism, elimination and toxicity. A number of studies have appeared in the recent literature on the identification of molecular frameworks, which correspond to the minimum structural subunit, in several drugs or lead-compounds, able of providing ligand points for more than one type of bioreceptor. Since Evans first introduced the concept of “privileged structure”, privileged-based drug discovery has emerged as a fruitful approach in medicinal chemistry. Privileged scaffolds increase hit rates for biological targets of interest, leading to the discovery of other biologically active targets and generating leads with enhanced drug-like properties. Consequently, medicinal chemists value privileged structures as core scaffolds for viable starting points in exploration design and synthesis. Despite the identification of numerous recurring molecular frameworks in bioactive molecules, there is a restricted availability of privileged structures. Toward this concern, a subject of great fascination and importance, dealing with the need to identify novel chemotypes, have been addressed the studies conducted during this PhD thesis. Research into drug-like and lead-like concepts has explored a range of ideas looking at structural characteristics and physicochemical properties. The selected structures might represent potential replacements of frequently occurring structural motifs. The development of efficient methodologies for the synthesis of the identified compounds has provided the suitable tools to open up an investigation about the behaviour of such a kind of molecules towards biological systems.