Synthesis and structure-activity relationships of pyrazine-pyridine biheteroaryls as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors was written by Kuo, Gee-Hong;Prouty, Catherine;Wang, Aihua;Emanuel, Stuart;DeAngelis, Alan;Zhang, Yan;Song, Fengbin;Beall, Lawrence;Connolly, Peter J.;Karnachi, Prahba;Chen, Xin;Gruninger, Robert H.;Sechler, Jan;Fuentes-Pesquera, Angel;Middleton, Steven A.;Jolliffe, Linda;Murray, William V.. And the article was included in Journal of Medicinal Chemistry in 2005.Synthetic Route of C6H5BrN2O2 This article mentions the following:
There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, I [R = NH(CH2)4OH, NH(CH2)2NMe2] exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of I were demonstrated in the A375 human melanoma xenograft nude mice model. Mol. modeling (QSAR anal.) was conducted in an attempt to rationalize the observed structure-activity relationship. In the experiment, the researchers used many compounds, for example, 6-Amino-5-bromonicotinic acid (cas: 180340-69-6Synthetic Route of C6H5BrN2O2).
6-Amino-5-bromonicotinic acid (cas: 180340-69-6) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Synthetic Route of C6H5BrN2O2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary