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.

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