From l-a-aminobutyric acid (Abu) a set of electrophilic and non-electrophilic replacements for the P1 cysteine of substrate and product inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase) serine protease have been synthesized and coupled to a model pentapeptide furnishing a set of hexapeptide inhibitors. Promising inhibitory activities with Ki values of 0.18 mM (P1 electrophilic a,b-unsatd. ketone), 0.46 mM (P1 electrophilic alkyl ketone) and 0.98 mM (P1 non-electrophilic alkenyl alc. as diastereomeric mixt.). The ref. hexapeptide product inhibitor had a Ki value of 1.54 mM (14, P1 Abu-OH). The electrophilic inhibitors exhibit increased potency as compared with the corresponding product inhibitor, and notably also the non-electrophilic P1 alkenyl alc. 10e. This represents the first example of non-electrophilic inhibitors that are not P1 amides or product inhibitors. [on SciFinder (R)]