Synthesis, Anti-Inflammatory And Analgesic Activities Of Some Benzene Ring-Substituted Derivatives Of Ilicifolius Alkaloids A

Objective:To study the synthesis, anti-inflammatory and analgesic activity of the benzene ring-substituted derivatives of Ilicifolius alkaloids A (4-Hydroxy-2-benzoxazolone, HBOA) and search for novel Nonsteroidal Anti-inflammato-ry Drugs with better efficacy.Methods:HBOA, obtained from 2-nitroresorcinol with reduction and subsequent condensation with urea by "one-pot-way", reacted with corresponding electrophilic reagents to yield target compounds TC-2-TC-4, of which the acylated ones were condensated with corresponding primary amines to afford Schiff Base derivatives TC-5～TC-10.The anti-inflammatory activities of the derivatives were screened by the xylene-induced mice ear swelling model and the HAc-induced mice peritoneal capillary permeability increase model.The analgesic activities of the derivatives were screened by the HAc-induced stretching test and hot-plate test. The influence of the derivatives upon the bleeding-time was measured by cutting the tail of mice.Results:Nine benzene ring-substituted derivatives of HBOA that had not been reported by literature were obtained, which structures were detemained by IR,1H-NMR,13C-NMR and MS.Derivatives TC-2～TC-5 and TC-7 showed marked anti-inflammatory activity comparable to Aspirin in xylene-induced mice ear swelling model.All the derivatives possessed some anti-inflammatory activity in HAc-induced mice peritoneal capillary permeability increase model.Among these derivatives, TC-2, TC-3, TC-9 and TC-10 exhibited significant anti-inflammatory activity stronger than Aspirin.All the derivatives showed marked analgesic activities comparable to Aspirin in HAc-induced stretching test, but none of them exhibited significant analgesic activities in hot-plate test.Compared with the control group, derivatives TC-3～TC-7 could significantly prolong the bleeding-time of mice, while the others hadn't marked influence upon it.Compared with the Aspirin group, derivatives TC-3 and TC-4 could significantly prolong the bleeding-time of mice, while the others hadn't marked influence upon it.Conclusion:Friedel-Crafts acylation, which possesses the advantages of easy control and stable yield, is an important appoach to synthesizing benzene ring-sbsutituted derivatives of HBOA.Derivatives TC-2 and TC-3 possess stronger anti-inflammatory activity than the others. Moreover, they also show marked analgesic activities comparable to Aspirin.So, target compounds TC-2 and TC-3 deserve further research.