title: Synthesis and evaluation of prodrugs for anti-angiogenic pyrrolylmethylidenyl oxindoles.
abstract: Potential prodrugs of inhibitors of VEGF-induced angiogenesis have been investigated. The prodrug systems studied were the 4-nitrobenzyl, 2-nitrophenylacetyl and 3-methyl-3-(3,6-dimethylbenzo-1,4-quinon-2-yl)butanoyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The anti-angiogenic compounds studied were the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its novel 6-hydroxy derivative. The potentially pro-anti-angiogenic compounds were assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents.
authors.affiliation: Peninsula Medical School, St. Luke's Campus, Exeter EX1 2LU, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Maskell
authors.forename: Emilie A
authors.initials: EA
authors.lastname: Blanche
authors.forename: Marie A
authors.initials: MA
authors.lastname: Colucci
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Whatmore
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011355:Prodrugs; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C116890:Semaxinib