Design,Synthesis And Bioactivity Studies Of Scutellarein

Objective:Scutellarin is a compound with clear pharmacological activity extracted from the Erigeron breviscapine(Vant.Hand.-Mazz.),which is widely used in the treatment of cardiovascular and cerebrovascular diseases.Its curative effect is exact with small side effects.However,there are some defects of Scutellarin,such as poor solubility and stability,low bioavailability,low brain distribution and weak activity.In view of the physical and chemical properties of scutellarin,based on the existing structure-activity relationship,we carried out targeted structural modification of scutellarein.It is hoped to obtain physical-chemical properties,bioavailability and activity of druggability better than scutellarin.Method:Based on the previous work of our research group,this paper optimized the structure of A and C rings of scutellarein,designed and synthesized two series of compounds.WSC-B series of optimizations which have good protective effects on cardiomyocytes were synthesized by our group.The A series of optimization retained the fluorine or trifluoromethyl group of 4’ position of B ring of WSC-B while different methylene amines were introduced by nucleophilic substitution reaction at 6 position of A ring in the hope of improving water solubility and bioavailability.The structure optimization of B series compounds was focused on the position 1 of C-ring of scutellarein.The active pharmacophores of scutellarein carbonyl and phenolic hydroxyl were retained,and the inactive position 1 was modified.In vitro activity results showed that HGF-A-Results:A and B series of 16 new compounds have been synthesized,which have not been reported.HGF-A-9 and HGF-A-11 in A series compounds and HGF-B-1、HGF-B-2、HGF-B-4 in B series compounds are better than scutellarein and WSC-B series compounds in antiplatelet aggregation visibly.ConclusionA series of compounds were designed and synthesized by analyzing the structure-activity relationship of scutellarein derivatives.Five derivatives with better activity were found by in vitro activity test.Hgf-A-9 and hgf-B-2,in particular,all inhibited collagen induced platelet aggregation.These five scutellarein derivatives deserve further research.