What is 2-methyl-5-nitropyridin-3-amine?

2-methyl-5-nitropyridin-3-amine is an intermediate for Flumatinib, an antineoplastic tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia (CML).

Brief introduction of Flumatinib

The chemical name of Flumatinib is 4-(4-Methyl-piperazin-1-ylmethyl)-N-[6-methyl-5-(4-pyridin-3-yl-pyrimidin-2-ylamino)-pyridin-3-yl]-3-trifluoromethyl-benzamide. Its molecular formula is C29H29F3N8O. Currently in China, it is at Phase I clinical trials for the treatment of chronic myelogenous leukemia (CML).
Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disease characterized by an overproduction of immature myeloid cells and mature granulocytes. CML is developed by the Philadelphia chromosome, a reciprocal chromosome translocation t(9;22), which causes a constitutive activation of the BCR-ABL tyrosine kinase (Deininger et al., 2000; Ren 2005). As a result, current CML treatment strategies involve the use of tyrosine kinase inhibitors, such as imatinib (Chemical name 4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide), nilotinib, and dasatinib (Sawyers, 2001; Kantarjian et al., 2006; Steinberg, 2007).

Flumatinib is like imatinib in structure, but nonclinical studies have shown that Flumatinib was predominantly metabolized by amide bond cleavage to yield two corresponding hydrolytic products. By comparison with imatinib, the electron-withdrawing groups of trifluoromethyl and pyridine facilitated the amide bond cleavage and led to the in vivo formation of a carboxylic acid and an amine. Therefore, Flumatinib is more potent in vitro and in vivo activity than imatinib when tested against leukemia cells expressing BCR-ABL (Sun et al., 2008).