Pyridine [2,3-d] Pyrimidine Derivatives, Synthesis And Biological Activity Study

EGFR-TK has recently been repoted as a new target for studying antitumor activeties. It's phosphorrylation plays an important role in regulating tumor growth and metastasis . High expression of EGFR has been associated with many type of tumor cell malignant proliferation. The study on inhibition of EGFR-TK has became a hot area of research.As find a highly effectul EGFR inhibitior that can guide the new development of new compound to treat cancer is a challenging task. Taking PD153035 as the lead compound, carbon atom at the 8-position of quinazoline ring is substituted by nitrogen atom. Starting from 2-aminonicotinic as the raw material,we have designed and synthesized two kinds of new-type pyrido[2,3-d]pyrimidine compounds: 16 4-amido-pyrido[2,3-d] pyrimidine and 4 4-S-substituted-pyrido[2,3-d]pyrimidine. The structures of all the 20 compouds are characterized by IR, ¹H NMR, ¹³C NMR and elemental analysis. The synthetic method for Pyrido[2,3-d]pydimidine-4-ol as the key intermediate is studied and optimized, the present method involving green microwave irradiation offers several advantages, such as fast reaction rate, high yield,lesser by produced with mimimal pollution.The in vitro anti-cancer activities of the 20 compounds are tested. The results showed that the 16 N-substituted-4-pyrido[2,3-d]pyrimidine compounds possessed weak anticancer activities. Howerer, one 4-S-substituted- pyrido[2,3-d]pyrimidine compound was found to display a distinct activity. This kind of compound with an inhibitory activity was not reported earlier. The investigation directs to identify an effective lead compound seeming worth of further research.