Pyrano[4,3-c]isoxazol-3-ones are found to be a new class of anti-leptospiral agents. Compounds 10g shows activity at concentration as low as 62.5 μg/mL. Pathogen specific In vitro activity: 12 pathogens and 1 non pathogen screened. In vivo: Inhibits leptospires in Cy-BALB/c mice by clearing renal colonization. In silico: Compound 10g binds with pathogen specific lipoprotein LipL32.