title: Rodent selectivity of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists: insights from a receptor model.
abstract: Rodent selectivity data of piperidine-4-yl-1H-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.
authors.affiliation: Lead Identification and Optimization Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany. Electronic address: jan.kriegl@boehringer-ingelheim.com.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Kriegl
authors.affiliation: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Domnic
authors.initials: D
authors.lastname: Martyres
authors.affiliation: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Grundl
authors.affiliation: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Anderskewitz
authors.affiliation: Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Dollinger
authors.affiliation: Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Rast
authors.affiliation: Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmid
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seither
authors.affiliation: Lead Identification and Optimization Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany.
authors.forename: Christofer S
authors.initials: CS
authors.lastname: Tautermann
mesh_terms: D000818:Animals; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D007211:Indoles; D010880:Piperidines; D054397:Receptors, CCR3; C032727:piperidine; C030374:indole
keywords: CCR3; Chemokine; Piperidine-4-yl-1H-indoles; Receptor model; Rodent selectivity; hERG