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

S Vendeville; L Bourel; E Davioud-Charvet; P Grellier; B Deprez; C Sergheraert

doi:10.1016/s0960-894x(99)00003-7

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

Bioorg Med Chem Lett. 1999 Feb 8;9(3):437-42. doi: 10.1016/s0960-894x(99)00003-7.

Authors

S Vendeville¹, L Bourel, E Davioud-Charvet, P Grellier, B Deprez, C Sergheraert

Affiliation

¹ Institut de Biologie de Lille-Institut Pasteur de Lille, URA CNRS 1309, Faculté de Pharmacie, Université de Lille II, France.

PMID: 10091698
DOI: 10.1016/s0960-894x(99)00003-7

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Isoquinolines / chemistry*
Prolyl Oligopeptidases
Protozoan Proteins
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology
Substrate Specificity

Substances

Isoquinolines
Protozoan Proteins
Serine Proteinase Inhibitors
Serine Endopeptidases
Prolyl Oligopeptidases
Tc80 prolyl oligopeptidase, Trypanosoma cruzi