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Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood

Thoma, Gebhard and Baenteli, Rolf and Lewis, Ian and Jones, Darryl and Kovarik, Jiri and Streiff, Markus and Zerwes, Hans-Guenter (2011) Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood. Bioorganic & Medicinal Chemistry Letters.

Abstract

The structure activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC50 values below 10 nM in both ligand binding and Ca2+-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC50 values below 10 nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.

Item Type: Article
Keywords: CXCR3, Ergoline, CXCL9, CXCL10, CXCL11
Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5084

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