STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OFCHALCONES AS SRS-A RECEPTOR ANTAGONISTS

A simple,reliable and highly sensitive bioasaay with sensitized longitudinal strips ofguinea pig ileum was used for screening the receptor antagonists of slow reacting substance ofanaphylaxis(SRS-A).The SRS-A receptor antagonistic activities of 17 chalcones were studied.Most compounds in thesechalcones were found to have SRS-A receptor antagonistic action at the concentration of 10^-4mol·L^-1.Among them, compounds 5,13 and 17 were highly effective with IC₅₀s of 7.5×10^-6,7.5×10^-6 and 6. 8×10^-5 mol-·L^-1,respectively.Under the same conditions, the IC₅₀ of FPL55712, a known leukotriene D₄ receptor antagonist,was shown to be 3×10^-4 mol·L^-1.It wouldappear that compounds 5,13 and 17 were 40,40 and 4.4 times more potent, respectively,than FPL55712.From analysis of structure-activity relationship of chalcones,these results suggest that thefollowing factors may be important for an active antagonist of SRS-A receptors:(a)There is a systemof π,π conjugation in the molecule,(b)The ester group in the B ring of chalcones is more favorablethan the carboxyl group;(c) Antagonism for meta-or para-substituted derivatives of carboxyl or estergroup in the B rigng are more potent than ortho-substituted compounds;(d)The length of carbon chainof alkyl group in the A ring of chalcones is more effective for 1, 4 or 6 carbon atoms than for 10 or 14 carbon atoms.