Acta Pharm. 63 (2013) 1-18

 

full paper

Original research paper

Synthesis and pharmacophore modeling of novel quinazolines bearing a biologically active sulfonamide moiety

MOSTAFA M. GHORAB, ZIENAB H. ISMAIL, AWWAD A. RADWAN and MOHAMAD ABDALLA

mmsghorab@yahoo.com

1 Medicinal, Aromatic and Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh, Riyadh 11451, Saudi Arabia

2 Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo, Egypt

3 Department of  Chemistry, Faculty of Science (Girl’s), Al-Azhar University, Cairo, Egypt

4 Kayyali Chair, Pharmaceutical Technology Center(PTC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

5 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut-71527, Egypt

6 Department of Organic Chemistry, Faculty of Pharmacy, October 6 University, Cairo, Egypt

Accepted October 4, 2012

 

In the present work, interaction of the strategic starting material, methyl 2-isothiocyanatobenzoate (1), with sulfa drugs resulted in the formation of methyl 2-[3-(4-(N-substituted sulfamoyl)phenyl)thioureido] benzoates 2-5, which upon reaction with hydrazine hydrate afforded N-amino derivatives 6–9. Triazoloquinazoline derivatives 10–18 were obtained via reaction of compounds 6–8 with aromatic aldehydes. Also, the reaction of compound 8 with formic acid gave the corresponding triazoloquinazoline derivative 19. Ttriazinoquinazoline derivatives 22, 23 were obtained via reaction of N-amino derivatives 6 or 8 with ethyl chloroacetate. Interaction of 6 with diethyloxalate yielded triazoloquinazoline 26. The synthesized compounds were screened for their in vitro antimicrobial activities and some of them exhibited promising antibacterial activity compared to ampicillin as positive control. Compounds that revealed significant activity are able to satisfy effectively the proposed pharmacophore geometry.

 

Keywords: quinazolines, fused quinazolines, sulfonamide, antimicrobial, pharmacophore