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

Abstract From a series of 4’-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4’-[3,5-bis(trifluoromethyl)-1 H -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 .