4-Quinolones comprise a series of synthetic antibacterial agents patterned after nalidixic acid. They have a proven track record over the past several decades for the treatment of bacterial infections. Their unique mechanism of action and bactericidal properties make them attractive therapeutic agents. Despite nearly forty years of research, quinolones still provide new analogues of both scientific and clinical interest. Compounds that are active against resistant strains, with improved pharmacokinetic and safety profiles are goals for current and future research in this area. In this book, you will find the method of synthesis of series of substituted 1,2,4-triazolo[1,5-a]pyrimidines and 1,2,4-triazolo[1,5-a]-1,3,5-triazines as nalidixic acid isosteres. You will also find the results of the in vitro antimicrobial assay of the synthesized compounds against a panel of Gram positive and Gram negative bacteria, and the yeast-like pathogenic fungus Candida albicans. In addition, the DNA-binding affinity of the synthesized compounds was also provided.