3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator

  • J Med Chem. 2000 Aug 10;43(16):2975-81. doi: 10.1021/jm990615a.
S W Djuric  1 ,  N Y BaMaung ,  A Basha ,  H Liu ,  J R Luly ,  D J Madar ,  R J Sciotti ,  N P Tu ,  F L Wagenaar ,  P E Wiedeman ,  X Zhou ,  S Ballaron ,  J Bauch ,  Y W Chen ,  X G Chiou ,  T Fey ,  D Gauvin ,  E Gubbins ,  G C Hsieh ,  K C Marsh ,  K W Mollison ,  M Pong ,  T K Shaughnessy ,  M P Sheets ,  M Smith ,  J M Trevillyan ,  U Warrior ,  C D Wegner ,  G W Carter
Affiliations
  • 1. Immunological Diseases Research, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064-6217, USA. [email protected]
PMID: 10956206 DOI: 10.1021/jm990615a
Abstract

A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a novel inhibitor of cytokine production. Identified initially as inhibitors of IL-2 synthesis, the BTPs have been optimized in this regard and even inhibit IL-2 production with a 10-fold enhancement over cyclosporine in an ex vivo assay. Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eotaxin production. Unlike the IL-2 inhibitors, cyclosporine and FK506, the BTPs do not directly inhibit the dephosphorylation of NFAT by Calcineurin.

Products