title: Novel 5-anilinoquinazoline-8-nitro derivatives as inhibitors of VEGFR-2 tyrosine kinase: synthesis, biological evaluation and molecular docking.
abstract: Vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibition is a well-established strategy to promptly tackle tumor growth by suppression of angiogenesis. We report herein a series of 5-anilinoquinazoline derivatives substituted by 1,3-disubstituted urea. All the newly synthesized compounds described were evaluated for VEGFR-2 kinase inhibition and antiproliferative activity against various cancer cells. The novel 1-aryl, 3-aryl-disubstituted urea quinazolines were effective VEGFR-2 kinase inhibitors with in vitro IC50 values in the submicromolar range (compound 6f, IC50 12.0 nM), but showed a weak to moderate inhibitory activity on cancer cells. Molecular interactions of the compounds were studied using molecular docking studies.
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xi
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Liu
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Zhang
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Yan
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009574:Nitro Compounds; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2