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Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases |
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| Authors: | David A. Sandham Nicola Arnold Heinrich Aschauer Kamlesh Bala Lucy Barker Lyndon Brown Zarin Brown David Budd Brian Cox Cerys Docx Gerald Dubois Nicholas Duggan Karen England Brian Everatt Marcus Furegati Edward Hall Frank Kalthoff Anna King Caroline Wilson |
| Affiliation: | 1. Novartis Institutes for Biomedical Research, Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom;2. Novartis Institutes for Biomedical Research, Brunnerstrasse 59, A1235 Vienna, Austria;3. Novartis Institutes for Biomedical Research, Basel Campus, CH-4002, Switzerland |
| Abstract: | 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. |
| Keywords: | CRTh2 receptor antagonist Allergy |
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