2. Academic Validation
  3. Design and synthesis of potent and orally active GPR4 antagonists with modulatory effects on nociception, inflammation, and angiogenesis

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

  • Bioorg Med Chem. 2017 Aug 15;25(16):4512-4525. doi: 10.1016/j.bmc.2017.06.050.
Wolfgang Miltz 1,  Juraj Velcicky 2,  Janet Dawson 3,  Amanda Littlewood-Evans 3,  Marie-Gabrielle Ludwig 4,  Klaus Seuwen 4,  Roland Feifel 5,  Berndt Oberhauser 2,  Arndt Meyer 2,  Daniela Gabriel 4,  Mark Nash 6,  Pius Loetscher 3
Affiliations

Affiliations

  • 1 Global Discovery Chemistry, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. Electronic address: wolfgang.miltz@novartis.com.
  • 2 Global Discovery Chemistry, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
  • 3 Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
  • 4 Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
  • 5 PK Sciences, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
  • 6 Muscoloskeletal Diseases, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
PMID: 28689977 DOI: 10.1016/j.bmc.2017.06.050
Abstract

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.

Keywords

Amino-pyrimidine derivatives; Angiogenesis; GPR4; Imidazo-pyridine derivatives; Inflammation; Pain.

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