Details

Autor(en) / Beteiligte

• HALL, Adrian
• BROWN, Susan H
• SCOCCITTI, Tiziana
• WILSON, Alexander W
• WINCHESTER, Wendy J
• BUDD, Christopher
• CLAYTON, Nicholas M
• GIBLIN, Gerard M. P
• GOLDSMITH, Paul
• HAYHOW, Thomas G
• HURST, David N
• NAYLOR, Alan
• RAWLINGS, D. Anthony

Titel

Discovery of GSK345931A : An EP1 receptor antagonist with efficacy in preclinical models of inflammatory pain

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2009-01, Vol.19 (2), p.497-501

Ort / Verlag

Amsterdam: Elsevier

Erscheinungsjahr

2009

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP1 receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 414.9 g/mol and poor in vivo metabolic stability in the rat and resulted in the identification of compound 7i (GSK345931A) which demonstrated good metabolic stability in the rat and lower molecular weight (381.9 g/mol). In addition, 7i (GSK345931A) showed measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain.