Hydroxyazoles as acid isosteres and their drug design applications—Part 1: Monocyclic systems

During the optimization process that leads to drug candidates, bioisosterism is often used to achieve improved potency/selectivity, optimal ADME-T profiles as well as reach intellectual property (IP). Hydroxyazoles, due to their acidity are considered isosteres of the carboxylic acid group, offering an efficient tool for designing active compounds with added IP value. Recently, we and other groups have explored the chemical space of these systems, shaping their applications in the framework of hit-to-lead optimization processes. This chapter covers the chemo-physical properties, synthetic methodologies, as well as the application in drug design, of monocyclic hydroxyazoles.