Macrolide antibiotics are a class of antibiotics that belong to the family of macrocyclic antibiotics. They contain a large macrocyclic lactone ring and generally consist of a central highly substituted lactone ring. There are three waves of macrolide development, starting with erythromycin, and progressing to newer derivatives with improved pharmacokinetics and ability to overcome bacterial resistance, such as azithromycin. Structure activity relationship studies showed that an amino sugar, lactone ring, and ketone group are important for antibacterial activity. Lead optimization efforts focused on modifications to increase acidic stability and effectiveness against resistant bacterial strains, such as through alkylation, ring expansion, or removal of the amino sugar to create ketol