Figure 7. Structure-Activity Relationships of a Panel of A1 Analogs.
A synthetic scheme for A1 and various analogs was devised and used prepare new compounds (please see Materials & Methods). The effects of various substitutions within the terminal phenyl ring of the A1 molecule (top panel) were evaluated in a C1s enzyme activity assay. The results were used to generate information on the structure-activity relationship of the A1 scaffold (bottom panel) in conjunction with the crystallographic information presented earlier (please see Fig. 5). Ki determinations are reported as the mean of three independent replicates.