1. Academic Validation
  2. Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile

Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile

  • Bioorg Med Chem Lett. 2012 Feb 15;22(4):1750-5. doi: 10.1016/j.bmcl.2011.12.092.
Graeme Semple 1 Juerg Lehmann Amy Wong Albert Ren Marc Bruce Young-Jun Shin Carleton R Sage Michael Morgan Wei-Chao Chen Kristen Sebring Zhi-Liang Chu James N Leonard Hussein Al-Shamma Andrew J Grottick Fuyong Du Yin Liang Keith Demarest Robert M Jones
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Arena Pharmaceuticals, San Diego, CA 92121, USA. GSemple@arenapharm.com
Abstract

The design and synthesis of a second generation GPR119-agonist clinical candidate for the treatment of diabetes is described. Compound 16 (APD597, JNJ-38431055) was selected for preclinical development based on a good balance between agonist potency, intrinsic activity and in particular on its good solubility and reduced drug-drug interaction potential. In addition, extensive in vivo studies showed a more favorable metabolic profile that may avoid the generation of long lasting metabolites with the potential to accumulate in clinical studies.

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