same, replacing 5-amino-2-methylbenzenesulfonamide with another arylamine at position 2 of the pyrimidine, gives inhibitory effect on VEGFR-2 and c-Kit. For R2, two groups can show this effect on the compound, an ether group on one, and on the other a chloride group. When substituents are added on pazopanib with different electronic effects at the benzene ring the inhibition to the kinase changes. Regarding the steric effect on position R1 and R2, a hydrogen in position R1 and a trifluoro-ether in R2 have the most inhibitory effect on VEGFR-2, which can be the effect of the electronegative groups. There is a steric hindrance of the indazole heterocycle, which can play an important role in the interaction with the tyrosine kinase receptor inhibition. Other small molecule VEGFR inhibitors Conjugated 3-(indolyl)- and 3-(azaindolyl)-4-arylmaleimide compounds can induce apoptosis in cancer cells and therefore may have use in cancer therapy, including colorectal and gastric adenocarcinoma. Oxetane 3,3-dicarboxamide compounds are possible inhibitors of tumor angiogenesis and metastasis, and may also be effective against viral infections. A 1,6-naphyridine-4-ketone fused heterocyclic derivative inhibits various kinases and the activity of tumor cells. The antifungal drug itraconazole may be and inhibitor for VEGFR-2 and could be used in treatments that VEGFR-2 plays a role. 3-phenyl-5-ureidoisothiazole-4-carboximide and 3-amino-5-phenylisothiazole derivatives inhibit, modulate and regulate tyrosine kinase signal and can be used for treatment of disorders that are caused by unregulated tyrosine kinase signal transduction, including cell growth, metabolic and blood vessel proliferative disorders. Thioether derivatives can be used to treat all forms of cancer and target multi target protein kinase inhibitors. Pharmacology Pharmacokinetics Pharmacokinetics of Quinoline and quinazoline-derivatives Absorption is variable within the group, with tmax ranging from 1–4 hours for Lenvatinib to 4–10 hours for cabozatinib. Food can slow down the absorption rate but should not affect the extent of the absorption. All drugs have high protein binding, ranging from 90-99%. Vandetanib and cabozatinib are metabolized mainly by CYP3A4, while lenvatinib is metabolized by CYP450 and via other pathways. The drugs are eliminated mostly in faeces, but also in urine. Vandetanib has a half-life of 19 days, while cabozatinib’s half-life is 99 hours. Pharmacokinetics of urea derivatives Regorafenib and sorafenib reach mean peak plasma level in about 3 or 4 hours after a single oral dose. A high-fat meal decreases their absorption, while a low-fat meal may increase it, in comparison to taking the drugs in a fasting condition. In vitro