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

Bioorg Med Chem. 2008 Nov 1;16(21):9457-66. doi: 10.1016/j.bmc.2008.09.047.

Yasuhiro Yonetoku ¹, Hirokazu Kubota, Yoji Miyazaki, Yoshinori Okamoto, Masashi Funatsu, Noriko Yoshimura-Ishikawa, Jun Ishikawa, Taiji Yoshino, Makoto Takeuchi, Mitsuaki Ohta

Affiliations

Affiliation

1 Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. [email protected]

PMID: 18835179 DOI: 10.1016/j.bmc.2008.09.047

Abstract

From a series of 4'-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4'-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,3-thiadiazole-5-carboxanilide, one inhibited thapsigargin-induced Ca2+ 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.

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