Study On The Synthesis And Antitumor Evaluation Of Quinazolinones Derivatives

Quinazolinone derivatives are important nitrogen-containing heterocyclic compounds with wide bioactivities,including anti-tumor,anti-hypertensive,anti-HIV,anti-TB,anti-inflammatory,anti-malarial and anti-bacterial.Among then its anti-tumor attracted special interests.Thus,its synthesis and bioactivity evaluation had alaway been a hotspot in organic chemistry and pharmaceutical chemistry.And this is the main research topic in the dissertation which consists of three chapters.In the first chapter the advance in the synthesis and anticancer evaluation of 2-substituted,2,3-disubstituted or polycyclic quinazolinone derivatives in recent years were reviewed.In the second chapter,the structural modification of an anticancer quinazolinone skeleton developed in our group were studied,in which the aromatic vinyl on 2-posistion of the quinazolinone skeleton was replaced by a benzyl.24 quinazolinone derivatives were synthesized in 4 steps starting from aryl acetic acid,anthranilic acid derivatives,N,N-dimethylethylenediamine,N,N-dimethyl-1,3-propylenediamine or 3-aminopropyl morpholin.The structure of the target compounds was identified and characterize by NMR,IR,MS.And their preliminary in vitro anti-tumor evaluation to MGC-803(gastric cancer cells),NCI-H460(lung cancer cells),HepG2(liver cells)were screened.In the third chapter,the isoelectric analogues of indenoisoquinoline,a well known privileged scaffold.as anticancer agents targeting to Topo 1 was design and synthesis in the guides of the theories such as "privileged structure" and "bio-isosterism alternation".34 aza-indenoisoquinoline derivatives bearing a quinazolinone motif were synthesized starting from 2-formyl benzoic acid,N,N-dimethylethylenediamine,N,N-dimethyl-1,3-propylenediamine,2-aminoethyl morpholin or 3-aminopropyl morpholin.The structure of the target compounds was identified and characterize by NMR,MS,and their ability to inhibit in vitro on MGC-803(gastric cancer cells),T24(bladder cancer),HepG2(liver cells)and Bel-7404(liver cells)were evaluated.