Design, Synthesis, And Biological Activity Studies Of Aza-indole And Aza-indolone Derivatives Based On Privileged Structures

The privilieged structure plays an important role in new drug discovered recentyears. This concept was present to provide a meaningful way for medicinal chemist tofind new drug moleculars. The synthesis methods and lead compound’s modificationwas spread basing the privilieged structure by many researchers. Meanwhile, moreand more privilieged frameworks join in the privilieged family. Thses scaffolds havebroad bioactivity, which has an important effect for the new found target spot.At the basis of above decription, we proceed two parts of work: the first one, westudy new synthesis method to get drug like molecular that was consisted of theprivilieged structure as the major scaffold rapidly, which is useful to build thescreening compound library. The compounds are obtained by theMCRs-GBB(Multi-Component Reactions-Groebke-lackburn-Bienaymé) reaction andthey are tricyclic fused N-heterocyclic systems contain the imidazo[1,2-a]pyridine asthe privilieged scaffold. We get18new framework compounds. The compounds mayhave the potential bioactivity for the new target spots. They have higher hits at theHTS(High Through-put Screening) for binding the new target.The second part is the research about SAR(Structure Activity Relationship) ofindirubin contain the privilieged stucture biindolone. The natural product indirubinwas discovered in1970s, and was proved having antitumor bioactivity. It is the maincomposition of Chinese traditional herbal medicine Qingdai in Danggui longhuiwan.This compound has significant curing effect to Chronic leukemia. After that, someresearchers found it have much other antitumor bioactivity to various cancer, such asMCF-7breast cancer, laryngeal cancer, LNCaP prostate cancer. So, we want todescribe the mechanism of the SAR by chemical modification. On the basis of that,we design some compounds using structural biology method, and found a few ofindirubin derivatives have not bad bioactivity to some new tagert spots.