Synthesis and antitumor activity of benzo[6″,7″]cyclohepta[1″,2″:4′,5′]pyrido[2′,3′-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones

Abstract

2-Thioxo-3,9,10,11-tetrahydro-1-phenyl-benzo[6′,7′]cyclohepta[1′,2′:4,5]pyrido[2,3-d]pyrimidin-4-one (4) was prepared by the reaction of 2-dimethylaminomethylenebenzosuberone (1) with 6-amino-1-phenyl-2-thioxo-2,3-dihydro-pyrimidin-4-one (2). 2-Hydrazino-9,10,11-trihydro-1-phenyl-benzo-[6′,7′]cyclohepta[1′,2′:4,5]pyrido[2,3-d]pyrimidin-4-one (5) was prepared in good yield by reaction of 4 with hydrazine hydrate under reflux. Reaction of compound 5 with different aldehydes in acetic acid gave the corresponding hydrazono derivatives 6. Cyclization of the latter compounds with bromine in acetic acid afforded a series of novel pentaheterocyclic compounds namely, 7,8,9-trihydro-4-phenyl-benzo[6″,7″]cyclohepta[1″,2″:4′,5′]pyrido[2′,3′-d][1,2,4]triazolo[4,3-a]pyrimidin-14-ones (7a–g). Some of the newly synthesized compounds showed potent antitumor activity against HEPG-2 “liver” cancer cell line and MCF-7 “breast” cancer cell line.

Keywords

• Hydrazones
• Penta-heterocyclic compounds
• Oxidative cyclization
• HEPG-2 “liver” cancer cell line
• MCF-7 “breast” cancer cell line