title: Synthesis and anti-angiogenic activity of 6-(1,2,4-thiadiazol-5-yl)-3-amino pyridazine derivatives.
abstract: General screening for inhibitors of microvessel growth in vitro in the rat aortic ring assay led to the discovery of a novel series of thiadiazole pyridazine compounds with potential anti-angiogenic activity. Chemical optimization produced orally active compounds with potent in vitro and in vivo anti-angiogenesis and anti-tumor activities.
authors.affiliation: Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium. jbongart@janbe.jnj.com
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bongartz
authors.forename: Raymond
authors.initials: R
authors.lastname: Stokbroekx
authors.forename: Marcel
authors.initials: M
authors.lastname: Van der Aa
authors.forename: Marcel
authors.initials: M
authors.lastname: Luyckx
authors.forename: Marc
authors.initials: M
authors.lastname: Willems
authors.forename: Marc
authors.initials: M
authors.lastname: Ceusters
authors.forename: Lieven
authors.initials: L
authors.lastname: Meerpoel
authors.forename: Gerda
authors.initials: G
authors.lastname: Smets
authors.forename: Tine
authors.initials: T
authors.lastname: Jansen
authors.forename: Walter
authors.initials: W
authors.lastname: Wouters
authors.forename: Charlie
authors.initials: C
authors.lastname: Bowden
authors.forename: Lisa
authors.initials: L
authors.lastname: Valletta
authors.forename: Mark
authors.initials: M
authors.lastname: Herb
authors.forename: Rose
authors.initials: R
authors.lastname: Tominovich
authors.forename: Robert
authors.initials: R
authors.lastname: Tuman
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D018827:Carcinoma, Lewis Lung; D046508:Culture Techniques; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011724:Pyridazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D011724:Pyridazines; D013830:Thiadiazoles