While amide-to-ester substitutions offer increased permeability, leading to increased flexibility in compound design, esters are also typically more susceptible to plasma-mediated hydrolysis, which can lead to low in vivo efficacy. For these amide-to-ester substitutions to be a viable option in drug development, it is crucial to compare the stability of ester and amide compounds. We incubated 1 -20 in human plasma at 37 ºC for 0, 15, 30, and 90 min to test this.