Synthesis and anti-angiogenic activity of 6-(1,2,4-thiadiazol-5-yl)-3-amino pyridazine derivatives.
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.
Bongartz
Jean-Pierre
JP
Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium. jbongart@janbe.jnj.com
Stokbroekx
Raymond
R
Van der Aa
Marcel
M
Luyckx
Marcel
M
Willems
Marc
M
Ceusters
Marc
M
Meerpoel
Lieven
L
Smets
Gerda
G
Jansen
Tine
T
Wouters
Walter
W
Bowden
Charlie
C
Valletta
Lisa
L
Herb
Mark
M
Tominovich
Rose
R
Tuman
Robert
R
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
D020533:Angiogenesis Inhibitors; D011724:Pyridazines; D013830:Thiadiazoles