Haemophilus influenzae (HI) is a significant human pathogen responsible for a range of diseases, from mild respiratory infections to severe invasive conditions including meningitis and septicemia. The rising incidence of HI infections, coupled with the limitations of current treatments and increasing antibiotic resistance highlights the urgent need for new therapeutic strategies. This research focuses on developing novel, specific, and potent inhibitors targeting HI Inosine Monophosphate Dehydrogenase (IMPDH), an enzyme critical for bacterial GTP synthesis. The feasibility of developing selective inhibitors is supported by structural and kinetic differences between bacterial and human IMPDH, as demonstrated by prior studies in other bacterial pathogens. The project will employ computational modelling of the enzyme to guide the design of new inhibitors, followed by synthesis and evaluation of their antibacterial activity and structure-activity relationships (SAR). This approach aims to address the growing challenge of antibiotic resistance in HI, filling a crucial gap in current treatment options.