As an alternative to nitriles and aldehydes, compounds with Michael acceptor moieties were investigated. Each of the three pairs consisted of one compound with the cinnamoyl group and the other with the 1H-indole-2-carbonyl capping group. Both vinyl sulfones exhibited significant CatL inhibition (12a, Ki = 625 nM; 12b, Ki = 243 nM). The Michael acceptor moiety present in 12a and 12b turned out to be advantageous in comparison with both the acrylamide (13a-b) and acrylonitrile (14a-b) warhead structures. The impact of the N-terminal capping group on the CatL-inhibitory potency was difficult to determine. In some cases (9a vs. 9b, 12a vs. 12b, 13a vs. 13b), the corresponding 1H-indole-2-carbonyl analog was more potent; in other cases (11a vs. 11b, 14a vs. 14b), the cinnamoyl counterpart. Overall, SARs of the dipeptide derivatives clearly indicated that the nature of the warhead group played a significant role in inhibiting the target CatL. In particular, it was discovered that the best warhead was the highly electrophilic aldehyde moiety. The rank order of potency for warhead groups in our CatL inhibitors was as follows: CHO > CN ≈ vinyl sulfone > pyridyl ester ≈ acrylonitrile ≈ acrylamide.