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

Authors
Djuric, SW BaMaung, NY Basha, A Liu, HQ Luly, JR Madar, DJ Sciotti, RJ Tu, NP Wagenaar, FL Wiedeman, PE Zhou, X Ballaron, S Bauch, J Chen, YW Chiou, XG Fey, T Gauvin, D Gubbins, E Hsieh, GC Marsh, KC Mollison, KW Pong, M Shaughnessy, TK Sheets, MP Smith, M Trevillyan, JM Warrior, U Wegner, CD Carter, GW
Citation
Sw. Djuric et al., 3,5-bis(trifluoromethyl)pyrazoles: A novel class of NFAT transcription factor regulator, J MED CHEM, 43(16), 2000, pp. 2975-2981
Citations number
35
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
00222623 → ACNP
Volume
43
Issue
16
Year of publication
2000
Pages
2975 - 2981
Database
ISI
SICI code
0022-2623(20000810)43:16<2975:3ANCON>2.0.ZU;2-6
Abstract
A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a nov el inhibitor of cytokine production. Identified initially as inhibitors of IL-2 synthesis, the BTPs have been optimized in this regard and even inhibi t IL-2 production with a 10-fold enhancement over cyclosporine in an ex viv o assay. Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eo taxin production. Unlike the IL-2 inhibitors, cycloseorine and FK506, the B TPs do not directly inhibit the dephosphorylation of NFAT by calcineurin.