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.
Vendeville
S
S
Institut de Biologie de Lille-Institut Pasteur de Lille, URA CNRS 1309, Faculté de Pharmacie, Université de Lille II, France.
Bourel
L
L
Davioud-Charvet
E
E
Grellier
P
P
Deprez
B
B
Sergheraert
C
C
D007546:Isoquinolines / Q000737:chemistry*; D000085822:Prolyl Oligopeptidases; D015800:Protozoan Proteins; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity
D007546:Isoquinolines; D015800:Protozoan Proteins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; C000705288:Tc80 prolyl oligopeptidase, Trypanosoma cruzi