A highly selective, p.o. bioavailable irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, N-[4-(3-chloro4-fluorophenylamino)-quinazolin-6-yl]-ac rylamide (CFPQA), was evaluated for its ability to prevent intestinal adenoma formation in ApcMin mice. Ten-week continuous dietary exposure to CFPQA at doses sufficient to abolish intestinal EGFR tyrosine phosphorylation...

A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also det...

In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphy...

In an effort to develop anticancer agents, a series of Mannich bases were prepared by Mannich reaction. When one biologically active molecule is linked to another, the resultant molecule generally has increased potency. Hence two pharmacophores, i.e. quinazoline ring and amine moiety are fused to obtain highly potent, more specific and less toxic agent. In the present study, synthesis of novel ...

We describe the structure-based design of a novel lead chemotype that binds to thumb pocket 2 of HCV NS5B polymerase and inhibits cell-based gt1 subgenomic reporter replicons at sub-micromolar concentrations (EC50<200nM). This new class of potent thumb pocket 2 inhibitors features a 1H-quinazolin-4-one scaffold derived from hybridization of a previously reported, low affinity thiazolone chemoty...

The reactions of 2-ethoxy-4-hydrazinoquinazoline 2 with diethyl oxalate and ethyl chloroacetate gave 6-ethoxy-2H-[1,2,4]triazino[4,3-c]quinazoline-3,4-dione 3 and 6-ethoxy-2,3-dihydro-4H-[1,2,4]triazino[4,3-c]quinazolin-4-one 4 respectively. A series of 5-ethoxy-2-X-[1,2,4]triazolo[1, 5-c]quinazolines 5a-d was also produced by reacting 2 with the acid chlorides namely: benzoyl, crotonyl, cinnam...

A series of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H) ones 6a-m have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-substituted phenylacrylamido-6,8-dibromoquinazolin-4(3H) ones 5a-m with hydrazine hydrate in the presence of glacial acetic acid. The chalcones 5a-m were prepared by the...

A highly selective, p.o. bioavailable irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, N-[4-(3-chloro-4-fluorophenylamino)-quinazolin-6-yl]-acrylamide (CFPQA), was evaluated for its ability to prevent intestinal adenoma formation in Apc mice. Ten-week continuous dietary exposure to CFPQA at doses sufficient to abolish intestinal EGFR tyrosine phosphorylation fa...

The 5-HT₃ receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT₃ hit fragment. Here we describe the synthesis and structure-activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesize...