A series of 4-aminoantipyrine derivatives were produced by condensing aromatic primary amine, namely, 4-aminoantipyrine with different aryl carbonyls which occurred cleanly and efficiently without using any catalyst at room temperature. Their structures were confirmed on the basis of 1 H NMR, IR, Mass spectra, and elemental analysis. The synthesized library was screened virtually using versatile bioinformatics parameters owing to the quick access, biological response, and utility of the produced moieties. The virtually screened molecules were subjected to screen practically against certain some strain of microorganisms: Staphylococcus aureus (Gram positive), Pseudomonas vulgaris (Gram positive), Pseudomonas Aeruginosa (Gram negative), and Escherichia coli (Gram negative). A correlation of structure and activities relationship of these compounds with respect to molecular modeling, Lipinski rule of five, drug-likeness, toxicity profiles, and other physico-chemical properties of drugs is described and verified experimentally.