title: Design and synthesis of novel quinazoline derivatives and their evaluation as PI3Ks inhibitors.
abstract: The aim of this work was to synthesize 4-acetamido-, 4-amino- and 4-oxo-6-substituted aminoquinazolines and to evaluate them as phosphoinositide 3-kinases (PI3Ks) inhibitors. The respective chemotype was designed based on combining the structural features of two previously reported scaffolds acting as potent PI3Kγ inhibitors, which are quinazoline derivatives and amino-heterocyclic derivatives. In vitro enzymatic assay at 10 µM against all the eight human PI3K isoforms showed that an unsubstituted benzamide group at position 6 and an acetyl group at N(4) gave the best inhibitory activity on PI3Kγ. Interestingly, compounds 5a and 5e showed a significant, inhibitory effect on Class II PI3K-C2γ. This is of high value since there are very few inhibitors for this isoform reported in the literature.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo.
authors.forename: Omar Maged
authors.initials: OM
authors.lastname: El-Said
authors.forename: Mostafa Mohamed
authors.initials: MM
authors.lastname: Hamed
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
authors.forename: Ashraf Hassan
authors.initials: AH
authors.lastname: Abadi
mesh_terms: D020134:Catalytic Domain; D015195:Drug Design; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines