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

Solution-phase automated parallel synthesis of a Tie-based library is descr ibed. This library comprising 2560 members, was obtained from the combinati on of 80 carboxylic acids and 32 amines and was screened against Tc80 prote ase, a parasitic prolyl endopeptidase secreted by Trypanosoma cruzi. Pyrrol idine derivatives proved the most potent inhibitors with IC50 values found in the low nanomolar range. (C) 1999 Elsevier Science Ltd. All rights reser ved.