From the enzymatic assay results (Table ), the groups with the best potency towards PL pro (XZ-3c and XZ-6a) and the (R)-1-(naphthalen-1-yl)ethan-1-amine from GRL-0617 are combined to form a new molecule, which should be able to achieve a higher potency than any of these molecules tested. Several synthetic pathways were tried, and only parallel synthesis afforded the final compound (Scheme 5). The target molecule was divided into two parts to do convergent synthesis. One of them coupled methyl glycinate with (E)-3-(4-(trifluoromethyl)phenyl)acrylic acid to give KH-7, and hydrolyze to give KH-8. The other synthesis was to hydrolyze methyl 2-amino-5-chlorobenzoate to form KH-9 and coupled with (R)-1-(naphthalen-1-yl)ethan-1-amine to form KH-10. KH-8 and KH-10 were then coupled using an NMI/MsCl-mediated reaction to form the target product (Scheme 7). Focusing on protease activity, the in vitro assay showed that changing the right side of the molecule to (R)-1-(naphthalen-1-yl)ethan-1-amine (KH-6a) or N 1 -(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethane-1,2-diamine (KH-6b) did not improve the potency (Table ). The combination of the best scaffolds from previous assays (KH-11) also did not improve the potency.