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ID: ALA1949629

Journal: Bioorg Med Chem Lett

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

Authors: Semple G, Lehmann J, Wong A, Ren A, Bruce M, Shin YJ, Sage CR, Morgan M, Chen WC, Sebring K, Chu ZL, Leonard JN, Al-Shamma H, Grottick AJ, Du F, Liang Y, Demarest K, Jones RM.

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.

CiteXplore: 22264481

DOI: 10.1016/j.bmcl.2011.12.092