24912-36-5Relevant academic research and scientific papers
Towards discovery of novel scaffold with potent antiangiogenic activity; design, synthesis of pyridazine based compounds, impact of hinge interaction, and accessibility of their bioactive conformation on VEGFR-2 activities
Jaballah, Maiy Y.,Serya, Rabah A. T.,Saad, Nasser,Khojah, Sohair M.,Ahmed, Marawan,Barakat, Khaled,Abouzid, Khaled A. M.
, p. 1573 - 1589 (2019/09/12)
Pyridazine scaffolds are considered privileged structures pertaining to its novelty, chemical stability, and synthetic feasibility. In our quest towards the development of novel scaffolds for effective vascular endothelial growth 2 (VEGFR-2) inhibition with antiangiogenic activity, four novel series of pyridazines were designed and synthesised. Five of the synthesised compounds; namely (8c, 8f, 15, 18b, and 18c) exhibited potent VEGFR-2 inhibitory potency (>80%); with IC50 values ranging from low micromolar to nanomolar range; namely compounds 8c, 8f, 15, 18c with (1.8 μM, 1.3 μM, 1.4 μM, 107 nM), respectively. Moreover, 3-[4-{(6-oxo-1,6-dihydropyridazin-3-yl)oxy}phenyl]urea derivative (18b) exhibited nanomolar potency towards VEGFR-2 (60.7 nM). In cellular assay, the above compounds showed excellent inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells at 10 μM concentration. Finally, an extensive molecular simulation study was performed to investigate the probable interaction with VEGFR-2.
N-substituted-N[3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]alkanamides, carbamates and ureas
-
, (2008/06/13)
Novel organic compounds which are N-substituted-N-[3-(1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]alkanamides, carbamates and ureas which are useful as anxiolytic or antiepileptic agents, methods of using the compounds, compositions of matter containing th
