Title of article :
TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs
Author/Authors :
Ted L. Underiner، نويسنده , , Bruce Ruggeri، نويسنده , , Lisa Aimone، نويسنده , , Mark Albom، نويسنده , , Thelma Angeles، نويسنده , , Hong Chang، نويسنده , , Robert L. Hudkins، نويسنده , , Kathryn Hunter، نويسنده , , Kurt Josef، نويسنده , , Candy Robinson، نويسنده , , Linda Weinberg، نويسنده , , Shi Yang، نويسنده , , Allison Zulli، نويسنده ,
Abstract :
Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further profiled in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.
Keywords :
Anti-angiogenic , Kinase inhibitor , VEGF-R2 , Tie-2 , VEGFR2
