Discovery of 7-azaindole derivatives as potent Orai inhibitors showing efficacy in a preclinical model of asthma. Issue 6 (15th March 2015)

• Record Type: Journal Article
• Authors: Esteve, Cristina; González, Jacob; Gual, Sílvia; Vidal, Laura; Alzina, Soledad; Sentellas, Sonia; Jover, Irene; Horrillo, Raquel; De Alba, Jorge; Miralpeix, Montserrat; Tarrasón, Gema; Vidal, Bernat
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 6(2015)
• Page Start: 1217
• Page End: 1222
• Publication Date: 2015-03-15
• Subjects: Orai inhibitors -- IL-2 inhibitors -- LAD2 -- CRAC channel -- OVA model; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.01.063
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Synthesis and SAR of a series of 7-azaindoles as Orai channel inhibitors showing good potency inhibiting IL-2 production in Jurkat cells is described. Compound14d displaying best pharmacokinetic properties was further characterized in a model of allergen induced asthma showing inhibition in the number of eosinophils in BALF. High lipophilicity remains as one of the main challenges for this class of compounds.