Tivozanib

Tivozanib (AV-951; KRN951) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC50s of 0.21, 0.16, and 0.24 nM in cell assay, respectively.

1-[2-chloro-4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-3-(5-methyl-3-isoxazolyl)urea is an aromatic ether.|Tivozanib has been used in trials studying the treatment and basic science of Solid Tumors, Glioblastoma, Ovarian Cancer, Prostate Cancer, and Stage IV Disease, among others.|Tivozanib is a Kinase Inhibitor. The mechanism of action of tivozanib is as a Tyrosine Kinase Inhibitor.|Tivozanib is an orally bioavailable inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 with potential antiangiogenic and antineoplastic activities. Tivozanib binds to and inhibits VEGFRs 1, 2 and 3, which may result in the inhibition of endothelial cell migration and proliferation, inhibition of tumor angiogenesis and tumor cell death. VEGFR tyrosine kinases, frequently overexpressed by a variety of tumor cell types, play a key role in angiogenesis.

3 - amino - 5 - methyl isoxazole (98 mg, 1 mmol) dissolved in anhydrous dichloromethane (5 ml) in, added under mixing N, N '- carbonyl diimidazole (356 mg, 2.2 mmol), then add 4 - [(4 (330 mg, 1 mmol) and tetrahydrofuran (5 ml) at 40 ° C under under stirring reaction 3 h, the reaction liquid under reducing pressure to dryness, re-dissolved in ethyl acetate (30 ml), and water extraction 3 times. The collection of ethyl acetate, reduced pressure to dryness, for column purification of silica gel chromatography (1 - 2percent methanol: dichloromethane). Collecting the corresponding elution component reducing dryness, methanol for refining, resulting in white or white solid powder for grips nepal fertile (394.6 mg, 87percent).A solution of 5-methylisoxazol-3-amine (5.3 g, 0.054 mol) and pyridine (17.2 g, 0.22 mol) in dimethylacetamide (30 mL) was stirred and cooled in an ice-water bath. Methyl chloroformate (5.1 g, 0.054 mol) was added slowly and keeping the reaction temperature below 10°C. The reaction mixturewas stirred at the ambient temperature for another 2 h to give the methyl (5-methylisoxazol-3-yl)carbamate (14). Then 2-cholo-4-((6, 7-dimethoxyquinolin-4-yl)oxy)-aniline 9 (12.0 g, 0.036 mol) was added and the reaction mixture was stirred at 80° C for 5 h. The reaction suspension was cooled to room temperature and added into water (300 mL) and MeOH (100 mL) and stirred for 30 min. The resulting solid was filtered, washed with water (50 mL × 2), and dried at 50°C to give the crude product 1, which was takenup in EtOAc : EtOH = 1:1 (v:v) (60 mL) and heated to reflux for 30 min, then cooled to room temperature for 1 h, the resulting solid was filtered off and washed with EtOAc (20 mL × 2), dried at 50°C for 3 h to afford 1 (12.9 g, 79percent) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 2.35 (s, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 6.52 (d, J = 5.2 Hz, 1H), 6.57 (d, J = 8.8 Hz, 1H), 7.28 (dd, J = 2.4, 8.8 Hz, 1H), 7.42 (s, 1H), 7.49 (s, 1H), 7.51 (d, J = 2.4 Hz, 1H), 8.21 (d, J = 8.8 Hz, 1H), 8.51 (d, J = 5.2 Hz, 1H), 9.02 (s, 1H), 10.42 (s, 1H). ESI-MS (m/z) 455.1 [M+H]+.HPLC: tR: 5.446 min, purity: 98.9percent.

Tivozanib is known as an oral VEGF receptor tyrosine kinase inhibitor, exhibiting antitumor effects towards renal cell carcinoma.. Tivozanib suppresses angiogenesis by selectively inhibiting against vascular endothelial growth factor.

Molecular Weight:454.9
XLogP3:4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:6
Exact Mass:454.1043974
Monoisotopic Mass:454.1043974
Topological Polar Surface Area:108
Heavy Atom Count:32
Complexity:631
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes