2. Academic Validation
  3. 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. [email protected]
PMID: 22264481 DOI: 10.1016/j.bmcl.2011.12.092
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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