Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor

Molecular docking and molecular dynamics simulation studies of GPR40 receptor–agonist interactions

“…In the many reported GPR40 agonists [10,11,13,14], parasubstituted phenyl propionic acid scaffold has emerged as a common structure motif, and compounds having an aromatic ring and an acid group have shown good agonistic activity. Both characteristics can be found in CA agonists such as GW9508 and TUG424 (Fig.…”

“…The first two of these combined give the docking energy while the first and third terms build up the binding energy. During all these interactions, the electrostatic interaction between ligands and receptor is the most important, because in most cases it can decide the binding strength and the location of ligand, while the hydrophobic interaction of some certain groups can affect the agonistic activity to a larger extent [10,11]. The energy information is listed in Table 1, and the interaction modes of the agonists and GPR40 are depicted in Fig.…”

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

“…Since GPCRs are involved in the regulation of insulin and glucagon secretion, they serve as potential drug targets. Several approaches have been undertaken to target GPCRs for new treatment (Garrido et al, 2006;McKeown et al, 2007).…”

Short Synthesis of Ethyl 3‐(3‐aminophenyl)propanoate

“…Chemical equivalents for synthons for the incorporation of the 3-(3-aminophenyl)propionyl moiety represent important building blocks in the synthesis of biologically active compounds, e.g., GPR40 receptor agonists [1], focal adhesion kinase inhibitors [2], agonists of the EP 2 receptor [3], and inhibitors of protein-tyrosine phosphatase [4].…”