Design and synthesis of potent and orally active GPR4 antagonists with modulatory effects on nociception, inflammation, and angiogenesis

Publication date: 15 August 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 16
Author(s): Wolfgang Miltz, Juraj Velcicky, Janet Dawson, Amanda Littlewood-Evans, Marie-Gabrielle Ludwig, Klaus Seuwen, Roland Feifel, Berndt Oberhauser, Arndt Meyer, Daniela Gabriel, Mark Nash, Pius Loetscher
GPR4, a G-protein coupled receptor, functions as a proton sensor being activated by extracellular acidic pH and has been implicated in playing a key role in acidosis associated with a variety of inflammatory conditions. An orally active GPR4 antagonist 39c was developed, starting from a high throughput screening hit 1. The compound shows potent cellular activity and is efficacious in animal models of angiogenesis, inflammation and pain.

Graphical abstract

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