Automated parallel synthesis of a tetrahydroisoquinolin-based library: potential prolyl endopeptidase inhibitors

Solution-phase automated parallel synthesis of a Tic-based library is described. This library comprising 2560 members, was obtained from the combination of 80 carboxylic acids and 32 amines and was screened against Tc80 protease, a parasitic prolyl endopeptidase secreted by Trypanosoma cruzi. Pyrrolidine derivatives proved the most potent inhibitors with IC50 values found in the low nanomolar range.