Rodent selectivity of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists: Insights from a receptor model. Issue 2 (15th January 2015)

• Record Type: Journal Article
• Authors: Kriegl, Jan M.; Martyres, Domnic; Grundl, Marc A.; Anderskewitz, Ralf; Dollinger, Horst; Rast, Georg; Schmid, Bernhard; Seither, Peter; Tautermann, Christofer S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 2(2015)
• Page Start: 229
• Page End: 235
• Publication Date: 2015-01-15
• Subjects: CCR3 -- Chemokine -- Piperidine-4-yl-1H-indoles -- Rodent selectivity -- hERG -- Receptor model; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2014.11.063
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Rodent selectivity data of piperidine-4-yl-1 H -indoles, a series of CC chemokine receptor-3 (CCR3) antagonists, are presented and discussed as part of an overall optimization effort within this lead compound class. Although attachment of an acidic moiety to the 1-position of the indole led to an overall balanced in vitro profile, in particular reducing inhibition of the hERG channel, potency on the rat and mouse receptor worsened. These findings could be rationalized in the context of a CCR3 homology model.