Title of article :
Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases
Author/Authors :
Reddeppareddy Dandu، نويسنده , , Allison L. Zulli، نويسنده , , Edward R. Bacon، نويسنده , , Ted Underiner، نويسنده , , Candy Robinson، نويسنده , , Hong Chang، نويسنده , , Sheila Miknyoczki، نويسنده , , Jennifer Grobelny، نويسنده , , Bruce A. Ruggeri، نويسنده , , Shi Yang، نويسنده , , Mark S. Albom، نويسنده , , Thelma S. Angeles، نويسنده , , Lisa D. Aimone، نويسنده , , Robert L. Hudkins، نويسنده ,
Abstract :
Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure–activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity.
Keywords :
VEGF-R2 , Tie-2 , tyrosine kinase inhibitors , angiogenesis
