Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases.

Autor: Sandham DA; Novartis Institutes for Biomedical Research, Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom. Electronic address: david.sandham@novartis.com., Arnold N, Aschauer H, Bala K, Barker L, Brown L, Brown Z, Budd D, Cox B, Docx C, Dubois G, Duggan N, England K, Everatt B, Furegati M, Hall E, Kalthoff F, King A, Leblanc CJ, Manini J, Meingassner J, Profit R, Schmidt A, Simmons J, Sohal B, Stringer R, Thomas M, Turner KL, Walker C, Watson SJ, Westwick J, Willis J, Williams G, Wilson C
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Nov 01; Vol. 21 (21), pp. 6582-91. Date of Electronic Publication: 2013 Aug 22.
DOI: 10.1016/j.bmc.2013.08.025
Abstrakt: Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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