Novel fluoro substituted benzo[b]pyran with anti-lung cancer activity

Abstract

6-Fluorobenzo[b]pyran-4-one <b style="">1</b> on condensation with aromatic aldehydes yields 3-arylmethylene-6-fluoro-2,3-dihydrobenzo[b]pyran-4-ones <b style="">2</b> which on treatment with phenylhydrazine and thiourea gives the pyrazole and pyrimidine thione derivatives <b style="">3</b> and <b style="">4</b>, respectively. Compound <b style="">4</b> reacts with chloroacetic acid in acetic acid-acetic anhydride mixture to afford the thiazolopyrimidines <b style="">5</b> which on condensation with aromatic aldehyde furnish the corresponding arylmethylene­thiazolopyrimidine derivatives <b style="">6</b>. The product <b style="">6</b> could be prepared directly by the action of chloroacetic acid and the proper aldehyde on <b style="">4</b> in the presence of acetic acid-acetic anhydride mixture. Product <b style="">2</b> reacts with malononitrile in the presence of ammonium acetate or piperidine to afford the pyridine- and pyran- <b style="">7</b> and <b style="">8</b> derivatives, respectively. Also, compound <b style="">1</b> on treatment with arylmethylenecyanoacetamide yields the pyridone derivatives <b style="">9</b>. Condensation of <b style="">1</b> with malononitrile affords the yliedinemalononitrile <b style="">10</b>, which on reaction with <i style="">p</i>-chlorobenzaldehyde-ammonium acetate or arylmethylene-cyano­acetamide yields the pyridine derivative <b style="">11</b> (isomer of <b style="">8</b>) and the dicarbonitrile derivative<b style=""> 12</b>, respectively. The synthesized compounds have been tested against three cell lines of human cancer (lung, breast and CNS cancer), and these compounds show anticancer activity at low concentration as compared to reference drug 5-fluorodeoxyuridine.