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Updated: Oct 7, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification
Sarah H Megahed1, Sari Rasheed2, Jennifer Herrmann2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835 Cairo, Egypt.
Abstract:
Bacterial resistance to currently used antibiotics demands the development of novel antibacterial agents with good safety margins and sufficient efficacy against multi-drug resistant isolates. We have previously described the synthesis of N-butyl-2-(butylthio)quinazolin-4-amine (I) as an optimized hit with broad-spectrum antibacterial activity and low cytotoxicity. In addition, we have identified a potential growing vector for this series of compounds. Herein, we describe further hit optimization which includes systematic diversifications of both the benzenoid part and the substituents at position 6 and 7 of compound I. Growing of the molecule beside the core modifications yielded several compounds with remarkable anti(myco)bacterial activity against a panel of pathogenic bacteria, including drug-resistant strains. Compound 12 showed a 2-4 fold improvement in activity than I against S. aureus Newman, S. pneumoniae DSM-20566 and E. faecalis DSM-20478. The compounds also showed a good safety profile towards human HepG2 cells.
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