title: Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold.
abstract: In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3-oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
authors.forename: Mai I
authors.initials: MI
authors.lastname: Shahin
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abou El Ella
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt. Electronic address: Khaled.abouzid@pharma.asu.edu.eg.
authors.forename: Khaled A M
authors.initials: KA
authors.lastname: Abouzid
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Docking study; Kinase; Quinoxaline; Type-II; VEGFR-2