Novel potent and selective Ca2+ release-activated Ca2+ (CRAC) channel inhibitors. Part 3: Synthesis and CRAC channel inhibitory activity of 4′-[(trifluoromethyl)pyrazol-1-yl]carboxanilides

From a series of 4 '-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4 '-[3,5-bis(tri- fluoromethyl)-1H-pyrazol-1-yl]-1,2,3-thiadiazole-5-carboxanilide, one inhibited thapsigargin-induced Ca(2+) influx in Jurkat T cells (IC(50) = 77 nM) and exhibited high selectivity for the CRAC channel over the VOC channel (index: > 130). Another acted as an inhibitor for both T lymphocyte activation-induced diseases and ovalbumin-induced airway eosinophilia in rats (ED(50) = 1.3 mg/kg) p.o. (C) 2008 Elsevier Ltd. All rights reserved.