.5,6,7 - Trimethoxy-substituted N-substituted Aromatic Ring -4 - Amino Quinazoline Compounds Synthesis And Anticancer Activity

With PD 153035 as the leading compound,a series of 5,6,7-trimethoxy-4-(N-aryl)-aminoquinazoline compounds were designed and synthesized.Starting from 2,3,4-trimethoxybenzoic acid,followed by nitration,esterification,reduction,cyclization and chlorination,key intermediate 4-chloro-5,6,7-trimethoxyquinazoline was obtained.Then different substituted anilines were reacted with the key intermediate giving the title 5,6,7-trimethoxy-4-(N-aryl)-aminoquinazoline compounds.The structures of the title compounds were elucidiated by elemental analysis,IR,¹H NMR,and ¹³C NMR spectra.Microwave method and conventional heating method were compared for the synthesis of all the title compounds.It was found that the title compounds could be obtained in shorter reaction time and high yields with easier workup procedure by using microwave method.Preliminary bioassay revealed that the title compounds had certain activity against PC3 and Bcap-37 cell proliferation.Among them the anti-proliferation activities of compounds I₃,I₆,I₇,I₈, I₉,I₁₁ and I₁₆ against PC3 cell were found to be 31.7%,32.6%,58.0%,6,38.9%,39.7%,49.6%,and 34.6%at 10μmol/L,resepectively.Compound I₁₆ showed high antitumor activity on Bcap-37 cell with the inhibition rate of 60.7%.Interestingly,compounds I₁,I₃ were found lower cytotoxic to PC3 cells.