title: Synthesis and pharmacophore modeling of novel quinazolines bearing a biologically active sulfonamide moiety.
abstract: 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. Triazinoquinazoline 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.
authors.affiliation: Medicinal, Aromatic and PoisonousPlants Research Center (MAPPRC) College of Pharmacy, King Saud University Riyadh, Riyadh, Arabia. mmsghorab@yahoo.com
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ghorab
authors.forename: Zienab H
authors.initials: ZH
authors.lastname: Ismail
authors.forename: Awwad A
authors.initials: AA
authors.lastname: Radwan
authors.forename: Mohamad
authors.initials: M
authors.lastname: Abdalla
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001565:Benzoates / Q000737:chemistry; D005658:Fungi / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry; D008024:Ligands; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013861:Thiocyanates / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D001565:Benzoates; D006834:Hydrazines; D008024:Ligands; D011799:Quinazolines; D013449:Sulfonamides; D013861:Thiocyanates; C570556:methyl 2-isothiocyanatobenzoate; C029424:hydrazine