Heterocyclic medicinal chemistry: development of innovative fragment library

Useful fragments for drug discovery are compounds synthesized in few steps, regioselectively functionalized using classic and modern methodologies, with fragment-like properties (e.g. clogP < 3 and MW < 300) and binding properties to specific macromolecular targets due to intrinsic pharmacophore in the structure. Recently, our research group have synthesized the so-called heteroaromatics rings of the future1 (Figure 1), including 2,6-naphtyridin-3-ol (1)2 and 1H-pyrazolo[3,4-c]pyridine-ol2 (2), that despite the good fragment-like properties show electronic complexity and polar functionalities that are prohibitive for applying the classic methodologies described in medicinal chemistry synthetic toolbox. Furthermore, we have explored the medicinal chemistry of furopyridines3 (Figure 1, 3). So, in this work we are showing successful strategies to decorate these complex heterocycles, in order to develop a structurally diverse small library of innovative heterocycles to populate the fragment chemical space.