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

Sandham, David A, Arnold, Nicola, Aschauer, Heinrich, Bala, Kamlesh, Barker, Lucy, Brown, Lyndon, Brown, Zarin, Budd, David, Cox, Brian, Docx, Cerys, Dubois, Gerald, Duggan, Nicholas, England, Karen, Everatt, Brian, Furegati, Marcus, Hall, Edward, Kalthoff, Frank, King, Anna, Leblanc, Catherine J, Manini, Jodie, Meingassner, Josef, Profit, Rachael, Schmidt, Alfred, Simmons, Jennifer, Sohal, Bindi, Stringer, Rowan, Thomas, Matthew, Turner, Katharine L, Walker, Christoph, Watson, Simon J, Westwick, John, Willis, Jennifer, Williams, Gareth and Wilson, Caroline (2013) Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases. Bioorganic & Medicinal Chemistry, 21 (21). pp. 6582-6591. ISSN 0968-0896

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry
Depositing User: Tom Gittoes
Date Deposited: 12 Jan 2015 12:01
Last Modified: 12 Jan 2015 12:01
URI: http://sro.sussex.ac.uk/id/eprint/52041
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